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Sample records for strongest activity ec50

  1. Annona muricata leaves have strongest cytotoxic activity against breast cancer cells

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    Susi Endrini

    2014-12-01

    Full Text Available Background Plant-derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. Plants have been the basis of traditional medicine throughout the world for thousands of years and are providing mankind with new remedies. The objective of this study was to determine the cytotoxicity of soursop (Anona muricata Linn leaves and pearl grass (Hedyotis corymbosa (L. Lam. on the hormone-dependent human breast carcinoma Michigan Cancer Foundation-7 (MCF-7 cell line. Methods This study used two types of solvents (water and ethanol in the extraction process and two incubation times (24 hours and 48 hours in the MTT assays to analyze the cytotoxic effects of both plants. Results Preliminary results showed that the ethanolic extract of soursop leaves (SE displayed cytotoxic effects against MCF-7 on 24- and 48-hour incubation times with IC50 values of 88.788 ìg/ml and 14.678 mg/ml, respectively. Ethanolic pearl grass extract (PE showed similar results, with IC50 values of 65.011 mg/ml on 24-hour incubation time and 52.329 mg/ml on 48-hour incubation time against MCF-7 cell line. However, the water extract of both plants displayed lower cytotoxic effect against MCF-7 cell line. Conclusion The ethanolic extract of both plants displayed cytotoxic effect against MCF-7. Soursop (Anona muricata Linn leaves have the strongest cytotoxic activity against MCF-7 breast cancer cell line.

  2. Annona muricata leaves have strongest cytotoxic activity against breast cancer cells

    Directory of Open Access Journals (Sweden)

    Susi Endrini

    2015-12-01

    Full Text Available BACKGROUND Plant-derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. Plants have been the basis of traditional medicine throughout the world for thousands of years and are providing mankind with new remedies. The objective of this study was to determine the cytotoxicity of soursop (Anona muricata Linn leaves and pearl grass (Hedyotis corymbosa (L. Lam. on the hormone-dependent human breast carcinoma Michigan Cancer Foundation-7 (MCF-7 cell line. METHODS This study used two types of solvents (water and ethanol in the extraction process and two incubation times (24 hours and 48 hours in the MTT assays to analyze the cytotoxic effects of both plants. RESULTS Preliminary results showed that the ethanolic extract of soursop leaves (SE displayed cytotoxic effects against MCF-7 on 24- and 48-hour incubation times with IC50 values of 88.788 μg/ml and 14.678 μg/ml, respectively. Ethanolic pearl grass extract (PE showed similar results, with IC50 values of 65.011 μg/ ml on 24-hour incubation time and 52.329 μg/ml on 48-hour incubation time against MCF-7 cell line. However, the water extract of both plants displayed lower cytotoxic effect against MCF-7 cell line. CONCLUSION The ethanolic extract of both plants displayed cytotoxic effect against MCF-7. Soursop (Anona muricata Linn leaves have the strongest cytotoxic activity against MCF-7 breast cancer cell line.

  3. ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

    Science.gov (United States)

    Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

    2015-02-01

    IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

  4. Mathematical modeling improves EC50 estimations from classical dose-response curves.

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    Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

    2015-03-01

    The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

  5. The dynamics of competitive activity performance of the strongest athletes in the world during the Olympic year

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    Rabin Muhammad Fahmi

    2016-12-01

    Full Text Available The paper scrutinizes the annual dynamics of competitive activity performance of prize winners in track and field of the Games of the XXXI Olympiad in Rio de Janeiro. The studies performed allow to identify two basic strategies of participation of elite athletes in the competitions. The first implies a strong focus on achieving the best results in major competitions of the year. It is used by most of the strongest athletes in the world. The second focuses the athlete on the effective combination of competitive activity in major competitions of the year (the Olympics and World Championships and in the Diamond League. As shown by the experience of the best sports practice, only a limited number of athletes manage to implement the latter strategy. The methodological approaches to planning competitive activity during the year are identified. The first involves the rational allocation of the optimal number of competitions throughout the year, the second focuses on preparatory competitive activities of a fairly high intensity, and the third involves the use of a small number of competitions in the system of annual training.

  6. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study.

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    Waschki, Benjamin; Kirsten, Anne; Holz, Olaf; Müller, Kai-Christian; Meyer, Thorsten; Watz, Henrik; Magnussen, Helgo

    2011-08-01

    Systemic effects of COPD are incompletely reflected by established prognostic assessments. We determined the prognostic value of objectively measured physical activity in comparison with established predictors of mortality and evaluated the prognostic value of noninvasive assessments of cardiovascular status, biomarkers of systemic inflammation, and adipokines. In a prospective cohort study of 170 outpatients with stable COPD (mean FEV(1), 56% predicted), we assessed lung function by spirometry and body plethysmography; physical activity level (PAL) by a multisensory armband; exercise capacity by 6-min walk distance test; cardiovascular status by echocardiography, vascular Doppler sonography (ankle-brachial index [ABI]), and N-terminal pro-B-type natriuretic peptide level; nutritional and muscular status by BMI and fat-free mass index; biomarkers by levels of high-sensitivity C-reactive protein, IL-6, fibrinogen, adiponectin, and leptin; and health status, dyspnea, and depressive symptoms by questionnaire. Established prognostic indices were calculated. The median follow-up was 48 months (range, 10-53 months). All-cause mortality was 15.4%. After adjustments, each 0.14 increase in PAL was associated with a lower risk of death (hazard ratio [HR], 0.46; 95% CI, 0.33-0.64; P leptin level (HR, 0.81; 95% CI, 0.65-0.99; P = .042), right ventricular function (Tei-index) (HR, 1.26; 95% CI, 1.04-1.54; P = .020), and ABI COPD. In addition, adiponectin level and vascular status provide independent prognostic information in our cohort.

  7. The median effective concentration (EC50) of propofol with different doses of fentanyl during colonoscopy in elderly patients.

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    Li, Shiyang; Yu, Fang; Zhu, Huichen; Yang, Yuting; Yang, Liqun; Lian, Jianfeng

    2016-04-21

    Propofol and fentanyl are the most widely administered anesthesia maintaining drugs during colonoscopy. In this study, we determined the median effective concentration (EC50) of propofol required for colonoscopy in elderly patients, and the purpose of this study was to describe the pharmacodynamic interaction between fentanyl and propofol when used in combination for colonoscopy in elderly patients. Ninety elderly patients scheduled for colonoscopy were allocated into three groups in a randomized, double-blinded manner as below, F0.5 group (0.5 μg.kg(-1) fentanyl), F1.0 group (1.0 μg.kg(-1) fentanyl) and saline control group. Anaesthesia was achieved by target-controlled infusion of propofol (Marsh model, with an initial plasma concentration of 2.0 μg.ml(-1)) and fentanyl. Colonoscopy was started 3 min after the injection of fentanyl. The EC50 of propofol for colonoscopy with different doses of fentanyl was measured by using an up-and-down sequential method with an adjacent concentration gradient at 0.5 μg.ml(-1) to inhibit purposeful movements. Anaesthesia associated adverse events and recovery characters were also recorded. The EC50 of propofol for colonoscopy in elderly patients were 2.75 μg.ml(-1) (95% CI, 2.50-3.02 μg.ml(-1)) in F0.5 group, 2.05 μg.ml(-1) (95% CI, 1.98-2.13 μg.ml(-1)) in F1.0 group and 3.08 μg.ml(-1) (95% CI, 2.78-3.42 μg.ml(-1)) in control group respectively (P fentanyl up to 1.0 μg.kg(-1) reduces the propofol EC50 required for elderly patients undergoing colonoscopy, and there was no significant difference in anaesthesia associated adverse events but prolonged awake and discharge time. Chinese Clinical Trial Registry ChiCTR15006368. Date of registration: May 3, 2015.

  8. Effects of Two Intranasal Dexmedetomidine Doses as Premedication on Sevoflurane EC50for Successful Laryngeal Mask Airway Placement in Children.

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    Xu, Jin; Deng, Xiao-Ming; Wei, Ling-Xin; Yang, Dong; Liu, Ju-Hui; Zhi, Juan; Li, Ya-Nan

    2016-12-20

    Objective To observe the effects of two different intranasal dexmedetomidine doses as premedication on the EC 50 of sevoflurane for successful laryngeal mask airway placement in children. Methods Children aged 3-6 years, of American Society of Anesthesiologists physical status 1, and scheduled for plastic surgery were enrolled in this study. Children were assigned to receive either spray administration of intranasal dexmedetomidine 1 μg/kg (group D1, n=21) or 2 μg/kg (group D2, n=20) approximately 30 minutes before anesthesia. Anesthesia was induced with sevoflurane up to 8% in 100% O 2 , with fresh gas flow set to 6 L/min. After the pupil fixed to the middle position, sevoflurane dial setting was reduced to 5% and fresh gas flow reduced to 3 L/min. The endtidal sevofluran (ET sevo ) concentration for laryngeal mask airway insertion sustained for 10 minutes after vein intubation, which was determined according to the Dixon's up and down method. The initial endtidal sevoflurane concentration in each group was set at 2%. ET sevo was increased/decreased (1:1.2) in the next patient according to the response to laryngeal mask airway insertion. Bispectral index, mask acceptance, all response to laryngeal mask airway insertion, and ET sevo of laryngeal mask airway insertion of children were recorded. Results The bispectral index value was 77.4±3.6 in group D2, which was significantly lower than that (87.4±1.9) in group D1 when children entered operation room (PMask acceptance was 76.2% in group D1 and 90.0% in group D2. The EC 50 of sevoflurane for laryngeal mask airway insertion was 1.09% (95% CI=0.89%-1.28%) in group D2, which was lower than 1.59% (95% CI=1.41%-1.78%) in group D1 (Plaryngeal mask airway placement in children.

  9. Acute toxicity of heavy metals to acetate-utilizing mixed cultures of sulfate-reducing bacteria: EC100 and EC50.

    Science.gov (United States)

    Utgikar, V P; Chen, B Y; Chaudhary, N; Tabak, H H; Haines, J R; Govind, R

    2001-12-01

    Acid mine drainage from abandoned mines and acid mine pit lakes is an important environmental concern and usually contains appreciable concentrations of heavy metals. Because sulfate-reducing bacteria (SRB) are involved in the treatment of acid mine drainage, knowledge of acute metal toxicity levels for SRB is essential for the proper functioning of the treatment system for acid mine drainage. Quantification of heavy metal toxicity to mixed cultures of SRB is complicated by the confounding effects of metal hydroxide and sulfide precipitation, biosorption, and complexation with the constituents of the reaction matrix. The objective of this paper was to demonstrate that measurements of dissolved metal concentrations could be used to determine the toxicity parameters for mixed cultures of sulfate-reducing bacteria. The effective concentration, 100% (EC100), the lowest initial dissolved metal concentrations at which no sulfate reduction is observed, and the effective concentration, 50% (EC50), the initial dissolved metal concentrations resulting in a 50% decrease in sulfate reduction, for copper and zinc were determined in the present study by means of nondestructive, rapid physical and chemical analytical techniques. The reaction medium used in the experiments was designed specifically (in terms of pH and chemical composition) to provide the nutrients necessary for the sulfidogenic activity of the SRB and to preclude chemical precipitation of the metals under investigation. The toxicity-mitigating effects of biosorption of dissolved metals were also quantified. Anaerobic Hungate tubes were set up (at least in triplicate) and monitored for sulfate-reduction activity. The onset of SRB activity was detected by the blackening of the reaction mixture because of formation of insoluble ferrous sulfide. The EC100 values were found to be 12 mg/L for copper and 20 mg/L for zinc. The dissolved metal concentration measurements were effective as the indicators of the effect of the

  10. Antiviral activity of Plantago major extracts and related compounds in vitro.

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    Chiang, L C; Chiang, W; Chang, M Y; Ng, L T; Lin, C C

    2002-07-01

    Plantago major L., a popular traditional Chinese medicine, has long been used for treating various diseases varying from cold to viral hepatitis. The aim of present study was to examine the antiviral activity of aqueous extract and pure compounds of P. major. Studies were conducted on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The antiviral activity of EC50 was defined as the concentration achieved 50% cyto-protection against virus infection and the selectivity index (SI) was determined by the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extract of P. major possessed only a slight anti-herpes virus activity. In contrast, certain pure compounds belonging to the five different classes of chemicals found in extracts of this plant exhibited potent antiviral activity. Among them, caffeic acid exhibited the strongest activity against HSV-1 (EC50=15.3 microg/ml, SI=671), HSV-2 (EC50=87.3 microg/ml, SI=118) and ADV-3 (EC50=14.2 microg/ml, SI=727), whereas chlorogenic acid possessed the strongest anti-ADV-11 (EC50=13.3 microg/ml, SI=301) activity. The present study concludes that pure compounds of P. major, which possess antiviral activities are mainly derived from the phenolic compounds, especially caffeic acid. Its mode of action against HSV-2 and ADV-3 was found to be at multiplication stages (postinfection of HSV-1: 0-12 h; ADV-3: 0-2 h), and with SI values greater than 400, suggesting the potential use of this compound for treatment of the infection by these two viruses.

  11. The Strongest Magnetic Field in Sunspots

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    Okamoto, J.; Sakurai, T.

    2017-12-01

    Sunspots are concentrations of magnetic fields on the solar surface. Generally, the strongest magnetic field in each sunspot is located in the dark umbra in most cases. A typical field strength in sunspots is around 3,000 G. On the other hand, some exceptions also have been found in complex sunspots with bright regions such as light bridges that separate opposite polarity umbrae, for instance with a strength of 4,300 G. However, the formation mechanism of such strong fields outside umbrae is still puzzling. Here we report an extremely strong magnetic field in a sunspot, which was located in a bright region sandwiched by two opposite-polarity umbrae. The strength is 6,250 G, which is the largest ever observed since the discovery of magnetic field on the Sun in 1908 by Hale. We obtained 31 scanned maps of the active region observed by Hinode/SOT/SP with a cadence of 3 hours over 5 days (February 1-6, 2014). Considering the spatial and temporal evolution of the vector magnetic field and the Doppler velocity in the bright region, we suggested that this strong field region was generated as a result of compression of one umbra pushed by the outward flow from the other umbra (Evershed flow), like the subduction of the Earth's crust in plate tectonics.

  12. Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

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    Tomohiro Koga

    Full Text Available To determine prognostic factors of clinically relevant radiographic progression (CRRP in patients with rheumatoid arthritis (RA achieving remission or low disease activity (LDA in clinical practice.Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs. CRRP was defined as the yearly progression of modified total Sharp score (mTSS >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC curve to estimate the performance of relevant variables for predicting CRRP.The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA positivity at baseline (OR = 15.2, 95%CI 2.64-299, time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45, and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42.ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

  13. Remifentanil halves the EC50 of propofol for successful insertion of the laryngeal mask airway and laryngeal tube in pediatric patients.

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    Park, Hye-Jin; Lee, Jeong-Rim; Kim, Chong Sung; Kim, Seong Deok; Kim, Hee-Soo

    2007-07-01

    Propofol and remifentanil are the drugs of choice for insertion of the supraglottic airway without muscle relaxants for short duration surgery. In this study, we compared propofol concentrations required for insertion of laryngeal mask way (LMA) or laryngeal tube (LT) with and without remifentanil. We included children scheduled for surgeries lasting airway device placement was determined using Dixon's up-and-down method. The concentration of propofol for consecutive patients in each group was determined by the response of the previous patient, using increments or decrements of 0.2 microg/mL. In patients receiving remifentanil, propofol EC50 for insertion of a LMA was 2.57 +/- 0.22 microg/mL and that of LT was 2.59 +/- 0.20 microg/mL (n.s.). In patients receiving saline, the corresponding values were 5.45 +/- 0.21 microg/mL and 5.58 +/- 0.23 microg/mL (n.s.). Conditions were excellent in 64% (9 of 14) and 79% (11 of 14) of patients receiving remifentanil, but in patients receiving saline, the values were 18% (2 of 11) for the LMA and 40.0% (4 of 10) for the LT. Remifentanil 7.5 ng/mL reduced the propofol concentration required for airway insertion by half, and improved conditions for insertion. Propofol concentrations for insertion of the LMA and LT were similar.

  14. The strongest magnetic fields in the universe

    CERN Document Server

    Balogh, A; Falanga, M; Lyutikov, M; Mereghetti, S; Piran, T; Treumann, RA

    2016-01-01

    This volume extends the ISSI series on magnetic fields in the Universe into the domain of what are by far the strongest fields in the Universe, and stronger than any field that could be produced on Earth. The chapters describe the magnetic fields in non-degenerate strongly magnetized stars, degenerate stars (such as white dwarfs and neutron stars), exotic members called magnetars, and in their environments, as well as magnetic fields in the environments of black holes. These strong fields have a profound effect on the behavior of matter, visible in particular in highly variable processes like radiation in all known wavelengths, including Gamma-Ray bursts. The generation and structure of such strong magnetic fields and effects on the environment are also described.

  15. Salomon: '97 E and P looking strongest in 9 years

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    Based on companies' disclosed spending plans, 1997 is shaping up to be the strongest year-ahead outlook in 9 years, according to Salomon Bros. Inc. Salomon Bros.' conclusion stems from its 15th annual survey of worldwide oil and gas exploration and production spending. The survey, released last month, included 125 US independents, 97 Canadian companies, 103 companies outside the US and Canada, and 15 majors. Significantly, when the 15% growth experienced in 1996 is combined with the 1997 outlook, it represents the strongest indicator of 2-year activity in the past 15 years, said Salomon Bros. Double-digit spending growth is projected in all regions for 1997, the analyst said. Salomon Bros. said a higher percentage of companies' E and P budgets are being allocated to offshore projects, driven in part by attractive prospects, 3D seismic technology, and increased operational efficiencies

  16. Effect of intranasal dexmedetomidine or oral midazolam premedication on sevoflurane EC50 for successful laryngeal mask airway placement in children: a randomized, double-blind, placebo-controlled trial.

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    Savla, Jyothi R; Ghai, Babita; Bansal, Dipika; Wig, Jyotsna

    2014-04-01

    This study was conducted to determine the effect of oral midazolam (OM) or intranasal dexmedetomidine (IND) on the EC50 of sevoflurane for successful laryngeal mask airway placement in children. We hypothesize that premedication with either agent might reduce the sevoflurane EC50 for laryngeal mask airway placement in children to a similar extent. Fifty-two American Society of Anesthesiologists (ASA) I children (aged 1-6 years) scheduled for general anesthesia with laryngeal mask airway were randomized to one of the three groups: group M received 0.5 mg · kg(-1) OM with honey and intranasal saline, group D received 2 μg · kg(-1) IND along with oral honey, and group P received oral honey and intranasal saline at least 30 min prior to induction of anesthesia. Anesthesia was induced with incremental sevoflurane up to 8% in 100% O2 . A predetermined target endtidal sevoflurane (ETsevo ) concentration (2% in the first child of all three groups) was sustained for 10 min before the attempt of laryngeal mask airway insertion by adjusting dial concentration. No intravenous anesthetic or neuromuscular blockade was used. ETsevo was increased/decreased (step size 0.2%) using Dixon's and Massey's up and down method in next patient depending upon previous patient's response. Placement of the laryngeal mask airway without movement, coughing, biting, or bucking was considered as successful. EC50 of sevoflurane was calculated as the average of the crossover midpoints in each group, which was further confirmed by probit analysis. The EC50 of sevoflurane for laryngeal mask airway placement after OM (1.66 ± 0.31) and IND (1.57 ± 0.14) premedications was significantly lower than the placebo group (2.00 ± 0.17, P mask airway insertion in children by 17% and 21%, respectively. © 2014 John Wiley & Sons Ltd.

  17. Fractionation and antioxidant activity potency of the extract of Garcinia lateriflora Blume var. javanica Boerl leaf

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    Mahayasih, Putu Gita Maya Widyaswari; Elya, Berna; Hanafi, Muhammad

    2018-02-01

    Garcinia lateriflora leaves extract of the family Guttiferae has been known to have excellent antioxidant activity. The objective of the study was to determine the antioxidant effect of the n-hexane, ethyl acetate and methanol extracts of G. lateriflora leaves extract. The antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging methods and Feric Reducing Antioxidant Power (FRAP) to determine the antioxidant properties. The extracts were fractionated by using column chromatography. The Methanol extract exhibited the strongest antioxidant activity with EC50 values are 13.95 and 19.65 µg/mL by DPPH and FRAP methods respectively. E13 fraction was the most active fraction from ethyl acetate extract with EC50 value for DPPH scavenging method was 37.14 µg/mL and 34.46 µg/mL for reducing power by the FRAP method. Meanwhile M3 fraction was the most active fraction in methanol extract with EC50 value for DPPH scavenging method was 50.02 µg/mL and 37.32 µg/mL for reducing power by the FRAP method.

  18. Antimicrobial activities of pyridinium-tailored pyrazoles bearing 1,3,4-oxadiazole scaffolds

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    Lei Zhou

    2017-11-01

    Full Text Available Herein, a series of pyridinium-tailored 5-trifluoromethylpyrazoles containing 1,3,4-oxadiazole moieties were constructed through coupling key pharmaceutical fragments of pyridinium, pyrazole, and 1,3,4-oxadiazole scaffolds in single molecular architecture. Antimicrobial results suggested that this kind of compounds exhibited significant activities against three types of pathogenic bacteria and six fungal strains in vitro. The minimal EC50 values of designed compounds against Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri could reach to 0.467, 1.04, and 0.600 μg/mL, respectively, through tuning and optimizing N-substituents, bridging atom, and alkyl length of the tailor. Antifungal assays revealed that all title molecules possessed considerable activity against Botrytis cinerea with the minimal EC50 value up to 2.71 μg/mL; and compounds I-8, I-10, I-12, II-12, and IV-12 showed the strongest growth suppression toward Rhizoctonia solani with EC50 values ranging from 10.2 to 24.0 μg/mL. Given the above results, this kind of compounds could serve as new lead compounds in the research of antimicrobial chemotherapy.

  19. Considering body mass differences, who are the world's strongest women?

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    Vanderburgh, P M; Dooman, C

    2000-01-01

    Allometric modeling (AM) has been used to determine the world's strongest body mass-adjusted man. Recently, however, AM was shown to demonstrate body mass bias in elite Olympic weightlifting performance. A second order polynomial (2OP) provided a better fit than AM with no body mass bias for men and women. The purpose of this study was to apply both AM and 2OP models to women's world powerlifting records (more a function of pure strength and less power than Olympic lifts) to determine the optimal model approach as well as the strongest body mass-adjusted woman in each event. Subjects were the 36 (9 per event) current women world record holders (as of Nov., 1997) for bench press (BP), deadlift (DL), squat (SQ), and total (TOT) lift (BP + DL + SQ) according to the International Powerlifting Federation (IPF). The 2OP model demonstrated the superior fit and no body mass bias as indicated by the coefficient of variation and residuals scatterplot inspection, respectively, for DL, SQ, and TOT. The AM for these three lifts, however, showed favorable bias toward the middle weight classes. The 2OP and AM yielded an essentially identical fit for BP. Although body mass-adjusted world records were dependent on the model used, Carrie Boudreau (U.S., 56-kg weight class), who received top scores in TOT and DL with both models, is arguably the world's strongest woman overall. Furthermore, although the 2OP model provides a better fit than AM for this elite population, a case can still be made for AM use, particularly in light of theoretical superiority.

  20. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile.

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    Sasagawa, Shinichi; Shimizu, Yutaka; Kami, Hideaki; Takeuchi, Takashi; Mita, Shizuka; Imada, Kazunori; Kato, Shigeaki; Mizuguchi, Kiyoshi

    2008-02-01

    Dienogest was introduced as an oral progestin. Yet its strong oral potency on endometrial activity is not clearly explained. To circumvent this situation, steroid hormone receptor profiling using transactivation assay and endometrial activity test in rabbits were carried out with determination of plasma drug concentration. Agonistic/antagonistic activity on human progesterone receptor (PR), androgen receptor (AR), glucocorticoid receptor (GR), mineralocorticoid receptor (MR), estrogen receptor alpha (ERalpha), or estrogen receptor beta (ERbeta) were determined. Dienogest activate PR (EC50=3.4 or 10.5 nmol/l) with antagonistic activity on AR (EC50=420.6 or 775.0 nmol/l) but not agonistic nor antagonistic action on GR, MR (3000 nmol/l). Dienogest activate neither ERalpha nor ERbeta (3000 nmol/l). Progesterone activated PR with antagonistic activity on AR and on MR. Dydrogesterone showed a similar profile to progesterone. Norethisterone activated PR, AR, and ERalpha. Medroxyprogesterone acetate activated PR, AR, and GR. Danazol activated PR and AR. Collectively, dienogest has a good specificity to PR compared with the other drugs. By oral treatment, dienogest showed the strongest endometrial activity (ED50=0.0042 mg/kg) in McPhail test among other progestins (ED50 values for MPA, DYG, NES were 0.074, 1.9, >0.05 mg/kg, respectively). Dienogest showed higher plasma concentrations than those of the other progestins with higher doses. The estimated plasma concentration of dienogest at ED50 (3.66 nmol/l) was close to its EC50 value to activate PR. Thus, the stronger oral activity of dienogest could be explained simply by its in vitro potency on PR and its oral pharmacokinetic profile.

  1. The Strength of the Strongest Ties in Collaborative Problem Solving

    DEFF Research Database (Denmark)

    de Montjoye, Yves-Alexandre; Stopczynski, Arkadiusz; Shmueli, Erez

    2014-01-01

    Complex problem solving in science, engineering, and business has become a highly collaborative endeavor. Teams of scientists or engineers collaborate on projects using their social networks to gather new ideas and feedback. Here we bridge the literature on team performance and information networks...... by studying teams' problem solving abilities as a function of both their within-team networks and their members' extended networks. We show that, while an assigned team's performance is strongly correlated with its networks of expressive and instrumental ties, only the strongest ties in both networks have......-significant in the statistical analysis. Our results have consequences for the organization of teams of scientists, engineers, and other knowledge workers tackling today's most complex problems....

  2. The Philippine tobacco industry: "the strongest tobacco lobby in Asia"

    Science.gov (United States)

    Alechnowicz, K; Chapman, S

    2004-01-01

    Objective: To highlight revelations from internal tobacco industry documents about the conduct of the industry in the Philippines since the 1960s. Areas explored include political corruption, health, employment of consultants, resisting pack labelling, and marketing and advertising. Methods: Systematic keyword Minnesota depository website searches of tobacco industry internal documents made available through the Master Settlement Agreement. Results: The Philippines has long suffered a reputation for political corruption where collusion between state and business was based on the exchange of political donations for favourable economic policies. The tobacco industry was able to limit the effectiveness of proposed anti-tobacco legislation. A prominent scientist publicly repudiated links between active and passive smoking and disease. The placement of health warning labels was negotiated to benefit the industry, and the commercial environment allowed it to capitalise on their marketing freedoms to the fullest potential. Women, children, youth, and the poor have been targeted. Conclusion: The politically laissez faire Philippines presented tobacco companies with an environment ripe for exploitation. The Philippines has seen some of the world's most extreme and controversial forms of tobacco promotion flourish. Against international standards of progress, the Philippines is among the world's slowest nations to take tobacco control seriously. PMID:15564224

  3. The Philippine tobacco industry: "the strongest tobacco lobby in Asia".

    Science.gov (United States)

    Alechnowicz, K; Chapman, S

    2004-12-01

    To highlight revelations from internal tobacco industry documents about the conduct of the industry in the Philippines since the 1960s. Areas explored include political corruption, health, employment of consultants, resisting pack labelling, and marketing and advertising. Systematic keyword Minnesota depository website searches of tobacco industry internal documents made available through the Master Settlement Agreement. The Philippines has long suffered a reputation for political corruption where collusion between state and business was based on the exchange of political donations for favourable economic policies. The tobacco industry was able to limit the effectiveness of proposed anti-tobacco legislation. A prominent scientist publicly repudiated links between active and passive smoking and disease. The placement of health warning labels was negotiated to benefit the industry, and the commercial environment allowed it to capitalise on their marketing freedoms to the fullest potential. Women, children, youth, and the poor have been targeted. The politically laissez faire Philippines presented tobacco companies with an environment ripe for exploitation. The Philippines has seen some of the world's most extreme and controversial forms of tobacco promotion flourish. Against international standards of progress, the Philippines is among the world's slowest nations to take tobacco control seriously.

  4. Linking algal growth inhibition to chemical activity

    DEFF Research Database (Denmark)

    Schmidt, Stine N.; Mayer, Philipp

    2015-01-01

    Recently, high-quality data were published on the algal growth inhibition caused by 50 non-polar narcotic compounds, of which 39 were liquid compounds with defined water solubility. In the present study, the toxicity data for these liquids were applied to challenge the chemical activity range...... for baseline toxicity. First, the reported effective concentrations (EC50) were divided by the respective water solubilities (Swater), since the obtained EC50/Swater ratio essentially equals the effective chemical activity (Ea50). The majority of EC50/Swater ratios were within the expected chemical activity...... solubility in the applied dataset. On an environmental risk assessment level, predicted no-effect concentrations (PNECs) for baseline toxicity could even be set as a percentage of saturation, which can easily be extended to mixtures. However, EC50 values well below 1% of liquid saturation can still occur...

  5. Studies on the antioxidant activity of the essential oil and methanol extract of Marrubium globosum subsp. globosum (lamiaceae) by three different chemical assays.

    Science.gov (United States)

    Sarikurkcu, Cengiz; Tepe, Bektas; Daferera, Dimitra; Polissiou, Moschos; Harmandar, Mansur

    2008-07-01

    This study is designed to examine the chemical composition and in vitro antioxidant activity of the essential oil and sub-fractions of the methanol extract of Marrubium globosum subsp. globosum. The GC and GC-MS analysis of the essential oil were resulted in the determination of 84 components representing 88.2% of the oil. The major constituents of the oil were spathulenol (15.8%), beta-caryophyllene (9.0%), caryophyllene oxide (7.9%), germacrene D (6.5%), and bicyclogermacrene (3.1%). Antioxidant activities of the samples were determined by three different test systems namely DPPH, beta-carotene/linoleic acid and reducing power assay. In DPPH system, the weakest radical scavenging activity was exhibited by the essential oil (1203.38+/-7.18 microg ml(-1)). Antioxidant activity of the polar sub-fraction of methanol extract was superior to the all samples tested with an EC(50) value of 157.26+/-1.12 microg ml(-1). In the second case, the inhibition capacity (%) of the polar sub-fraction of methanol extract (97.39%+/-0.84) was found the strongest one, which is almost equal to the inhibition capacity of positive control BHT (97.44%+/-0.74). In the case of reducing power assay, a similar activity pattern was observed as given in the first two systems. Polar sub-fraction was the strongest radical reducer when compared with the non-polar one, with an EC(50) value of 625.63+/-1.02 microg ml(-1). The amount of the total phenolics was highest in polar sub-fraction (25.60+/-0.74 microg/mg). A positive correlation was observed between the antioxidant activity potential and total phenolic level of the extracts. On the other hand, total flavonoid content was found equal for the both sub-fractions.

  6. Strongest Tropical cyclones: 1980-2009: A 30-year collage of Hurricane Satellite (HURSAT) data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Strongest Tropical Cyclones: 1980-2009 poster - a 30-year collage of Hurricane Satellite (HURSAT) data. This poster depicts a series of 5 degree grids where within...

  7. Caregiver burden: the strongest predictor of self-rated health in caregivers of patients with dementia.

    Science.gov (United States)

    Abdollahpour, Ibrahim; Nedjat, Saharnaz; Noroozian, Maryam; Salimi, Yahya; Majdzadeh, Reza

    2014-09-01

    People having dementia need help and supervision to perform their activities of daily living. This responsibility is usually imposed on family members who endure a great burden, leading to undesirable health outcomes. The aims of our study were to measure caregivers' health as well as identify its adjusted relevant predictors. One hundred and fifty three registered patients and their caregivers from Iranian Alzheimer Association were included in this cross-sectional study through sequential sampling. Self-rated health (SRH) was measured using a single question with Likert-type scale ranging from very bad (1) to very good (5). The multiple linear regression model was applied to determine the adjusted associations between independent variables under study and SRH. The mean caregiver SRH level was 3.03. Of the participant caregivers, 29% were either unsatisfied or very unsatisfied with their health level. In the final regression model, SRH showed a direct significant association with the patient's number of children but an inverse significant association with the marital status (married patients), patient's age, and caregiver burden. Caregiver burden was not only significantly associated with poor SRH after removing the effect of the other covariates but it was also recognized as the strongest predictor of caregivers' SRH. Therefore, it seems that development of intervention programs, in order to reduce caregiver burden, can be considered as important step in promoting caregivers' health level. © The Author(s) 2014.

  8. State Funding for Students with Disabilities. ECS 50-State Review

    Science.gov (United States)

    Millard, Maria; Aragon, Stephanie

    2015-01-01

    About 13 percent of all public school students receive special educational services and state spending for these students is rising. In Michigan, for example, spending rose 60 percent from 2000 to 2010. While service costs have been increasing, the share of the costs covered by federal funding has been decreasing. Six years ago, the Individuals…

  9. ON POTENTIAL REPRESENTATIONS OF THE DISTRIBUTION LAW OF RARE STRONGEST EARTHQUAKES

    Directory of Open Access Journals (Sweden)

    M. V. Rodkin

    2014-01-01

    'bend-down' is described by the finite distribution law, i.e. the bend-down occurs more efficiently than it is envisaged in the commonly used model developed by Y. Kagan (which treats the bend-dawn as an exponential decay law. However, despite the finiteness of the distribution law, density of magnitudes decline quite slowly in the area close to the maximum possible Мmах event as (Мmах – Mn, where n varies in the range between 4 and 6 in the majority of cases. As a result Мmах value can be estimated only with a large error. In rare cases, if the space-and-time area under study contains higher number of strongest earthquakes, the empirical distribution law becomes close to the exponential law; in this case n value is quite high, and Мmах values becomes unstable and tend to infinite growth.In our study, the distribution law of strongest earthquakes was investigated by the methods based on the extreme values theory (world data and several regional catalogues were examined, and the results of calculation do not reveal cases of  occurrence of characteristic events. However, such a seismic regime was revealed in a number of cases from paleoseismicity data and from some instrumental regional catalogues. Conditions providing for the occurrence of characteristic earthquakes are studied here using the multiplicative cascade model. According to [Rodkin, 2011], this model provides the simulation of all known regularities of seismic regime, such as a decrease in b-value in the vicinity of strong earthquakes, development of aftershock power cascade, and existence of seismic cycle and foreshock activity. This article considers an extension of the cascade model by adding of non-linear members in the kinetic cascade equation in order to describe effects of the 'bend-down' of the earthquake recurrence curve and the characteristic earthquakes occurrence. It is shown that in terms of the multiplicative cascade model, the occurrence of characteristic earthquakes is connected

  10. Diffusive versus Displacive Contact Plasticity of Nanoscale Asperities: Temperature- and Velocity-Dependent Strongest Size.

    Science.gov (United States)

    Guo, Wei; Wang, Zhao; Li, Ju

    2015-10-14

    We predict a strongest size for the contact strength when asperity radii of curvature decrease below 10 nm. The reason for such strongest size is found to be correlated with the competition between the dislocation plasticity and surface diffusional plasticity. The essential role of temperature is calculated and illustrated in a comprehensive asperity size-strength-temperature map taking into account the effect of contact velocity. Such a map should be essential for various phenomena related to nanoscale contacts such as nanowire cold welding, self-assembly of nanoparticles and adhesive nanopillar arrays, as well as the electrical, thermal, and mechanical properties of macroscopic interfaces.

  11. Synthesis and 2D-QSAR studies of neolignan-based diaryl-tetrahydrofuran and -furan analogues with remarkable activity against Trypanosoma cruzi and assessment of the trypanothione reductase activity.

    Science.gov (United States)

    Hartmann, Ana Paula; de Carvalho, Marcelo Rodrigues; Bernardes, Lilian Sibelle Campos; Moraes, Milena Hoehr de; de Melo, Eduardo Borges; Lopes, Carla Duque; Steindel, Mario; da Silva, João Santana; Carvalho, Ivone

    2017-11-10

    Two series of diaryl-tetrahydrofuran and -furan were synthesised and screened for anti-trypanosomal activity against trypomastigote and amastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. Based on evidence that modification of a natural product may result in a more effective drug than the natural product itself, and using known neolignan inhibitors veraguensin 1 and grandisin 2 as templates to synthesise simpler analogues, remarkable anti-trypanosomal activity and selectivity were found for 3,5-dimethoxylated diaryl-furan 5c and 2,4-dimethoxylated diaryl-tetrahydrofuran 4e analogues with EC 50 0.01 μM and EC 50 0.75 μM, respectively, the former being 260-fold more potent than veraguensin 1 and 150-fold better than benznidazole, the current available drugs for Chagas disease treatment. The ability of the most potent anti-trypanosomal compounds to penetrate LLC-MK2 cells infected with T. cruzi amastigotes parasite was tested, which revealed 4e and 5e analogues as the most effective, causing no damage to mammalian cells. In particular, the majority of the derivatives were non-toxic against mice spleen cells. 2D-QSAR studies show the rigid central core and the position of dimethoxy-aryl substituents dramatically affect the anti-trypanosomal activity. The mode of action of the most active anti-trypanosomal derivatives was investigated by exploring the anti-oxidant functions of Trypanothione reductase (TR). As a result, diarylfuran series displayed the strongest inhibition, highlighting compounds 5d-e (IC 50 19.2 and 17.7 μM) and 5f-g (IC 50 8.9 and 7.4 μM), respectively, with similar or 2-fold higher than the reference inhibitor clomipramine (IC 50 15.2 μM). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity

    Directory of Open Access Journals (Sweden)

    Armando Escobar-Ramos

    2017-08-01

    Full Text Available Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1; 3-deoxysappanchalcone (2; three homoisoflavonoids known as hematoxylol A (3; 4-O-methylhematoxylol (4; and, hematoxin (5. The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum, and allowed to demonstrate that the methanolic extract (EC50 = 62.11 ± 3.23 fractions HcF7 (EC50 = 61.75 ± 3.55 and HcF9 (EC50 = 125.5 ± 10.65 and compounds 1 (EC50 = 16.06 ± 2.15 and 2 (EC50 = 25.37 ± 3.47 of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC50 = 20.08 ± 2.0 as a positive control.

  13. Antioxidant, Antitubercular and Cytotoxic Activities of Piper imperiale

    Directory of Open Access Journals (Sweden)

    Sanjib Bhakta

    2012-04-01

    Full Text Available Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to 6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin, ferulic acid, resveratrol and quercetin were identified and quantified by HPLC. DPPH and ABTS assays showed high antioxidant activity of the leaf extract (EC50ABTS = 15.6 µg/mL, EC50DPPH = 27.3 µg/mL with EC50 in the same order of magnitude as the hydroxyquinone (EC50ABTS = 10.2 µg/mL, EC50DPPH = 15.7 µg/mL. The flower extract showed strong antimicrobial activity against Mycobacterium tuberculosis H37Rv. All the extracts exhibited dose-dependent cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper extract has been found to be highly active against M. tuberculosis. This study shows the biological potential of Piper imperiale extracts and gives way to bio-guided studies with well-defined biological activities.

  14. Phenolic Constituents and Inhibitory Effects of Hibiscus sabdariffa L. (Sorrel) Calyx on Cholinergic, Monoaminergic, and Purinergic Enzyme Activities.

    Science.gov (United States)

    Oboh, Ganiyu; Adewuni, Taiwo M; Ademiluyi, Adedayo O; Olasehinde, Tosin A; Ademosun, Ayokunle O

    2018-01-17

    This study revealed the effect of phenolic extract from Hibiscus sabdariffa L. (sorrel) calyx on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), and ecto-5' nucleotidase (E-NTDase) activities as well as pro-oxidant-induced oxidative damage in rat brain in vitro. Sorrel extract inhibited AChE (EC 50 = 46.96 µg/mL), BChE (EC 50 = 40.38 µg/mL), MAO (EC 50 = 43.69 µg/mL), and E-NTDase (EC 50 = 40.52 µg/mL) and stimulated Na + /K + -ATPase (EC 50 = 22.01 µg/mL) activities. The phenolic extract also reduced Fe 2+ - (EC 50 = 22.37 µg/mL) and sodium nitroprusside- (SNP-) (21.46 µg/mL) induced malondialdehyde (MDA) production in rat brain homogenates. Catechin (53.12 mg/g), chlorogenic (67.12 mg/g), rutin (16.25 mg/g), and caffeic acid (15.38 mg/g) were the most abundant phenolic compounds in the extract. The synergistic effects of the phenolic compounds may contribute to the enzyme inhibitory and stimulatory activities of the extract. Our findings suggest that sorrel extract shows promising potential for the treatment and/or management of some neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

  15. Muscle quality and relative adiposity are the strongest predictors of lower-extremity physical function in older women.

    Science.gov (United States)

    Straight, Chad R; Brady, Anne O; Evans, Ellen M

    2015-01-01

    The aim of this study was to examine the relative contributions of physical activity, adiposity, lean mass and muscle quality to lower-extremity physical function (LEPF) in older women. Cross-sectional analysis at a university research laboratory. Community-dwelling older women (n=96, 73.9 ± 5.6 years, BMI=26.5 ± 4.7 kg/m(2)) were assessed for body composition via dual-energy X-ray absorptiometry, leg extension power using the Nottingham power rig, muscle quality (W/kg) as the ratio of leg extension power (W) to lower-body mineral free lean mass (kg) and moderate-intensity physical activity via questionnaire. A composite measure of LEPF was calculated by summing Z-scores of the 6-min walk, 8-foot up-and-go and 30-s chair stand tests. Muscle quality and physical activity were associated with all measures of LEPF (all p0.05). Hierarchical linear regression analyses revealed that muscle quality (standardized β=0.47, pquality and relative adiposity are the strongest independent predictors of LEPF in older women. These findings suggest that maintaining muscle quality, especially relative to adiposity, may be a critical target for interventions to prevent declines in physical function in older women. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Timed Stair Climbing is the Single Strongest Predictor of Perioperative Complications in Patients Undergoing Abdominal Surgery

    Science.gov (United States)

    Reddy, Sushanth; Contreras, Carlo M; Singletary, Brandon; Bradford, T Miller; Waldrop, Mary G; Mims, Andrew H; Smedley, W Andrew; Swords, Jacob A; Thomas N, Wang; Martin J, Heslin

    2016-01-01

    Background Current methods to predict patients' peri-operative morbidity utilize complex algorithms with multiple clinical variables focusing primarily on organ-specific compromise. The aim of the present study is to determine the value of a timed stair climb (SC) in predicting peri-operative complications for patients undergoing abdominal surgery. Study Design From March 2014 to July 2015, 362 patients attempted SC while being timed prior to undergoing elective abdominal surgery. Vital signs were measured before and after SC. Ninety day post-operative complications were assessed by the Accordion Severity Grading System. The prognostic value of SC was compared to the ACS NSQIP risk calculator. Results A total of 264 (97.4%) patients were able to complete SC. SC time directly correlated to changes in both mean arterial pressure and heart rate as an indicator of stress. An Accordion grade 2 or higher complication occurred in 84 (25%) patients. There were 8 mortalities (2.4%). Patients with slower SC times had an increased complication rate (P<0.0001). In multivariable analysis SC time was the single strongest predictor of complications (OR=1.029, P<0.0001), and no other clinical co-morbidity reached statistical significance. Receiver operative characteristic curves predicting post-operative morbidity by SC time was superior to that of the ACS risk calculator (AUC 0.81 vs. 0.62, P<0.0001). Additionally slower patients had a greater deviation from predicted length of hospital stay (P=0.034) Conclusions SC provides measurable stress, accurately predicts post-operative complications, and is easy to administer in patients undergoing abdominal surgery. Larger patient populations with a diverse group of operations will be needed to further validate the use of SC in risk prediction models. PMID:26920993

  17. Gamma band plasticity in sensory cortex is a signature of the strongest memory rather than memory of the training stimulus.

    Science.gov (United States)

    Weinberger, Norman M; Miasnikov, Alexandre A; Bieszczad, Kasia M; Chen, Jemmy C

    2013-09-01

    Gamma oscillations (∼30-120Hz) are considered to be a reflection of coordinated neuronal activity, linked to processes underlying synaptic integration and plasticity. Increases in gamma power within the cerebral cortex have been found during many cognitive processes such as attention, learning, memory and problem solving in both humans and animals. However, the specificity of gamma to the detailed contents of memory remains largely unknown. We investigated the relationship between learning-induced increased gamma power in the primary auditory cortex (A1) and the strength of memory for acoustic frequency. Adult male rats (n=16) received three days (200 trials each) of pairing a tone (3.66 kHz) with stimulation of the nucleus basalis, which implanted a memory for acoustic frequency as assessed by associatively-induced disruption of ongoing behavior, viz., respiration. Post-training frequency generalization gradients (FGGs) revealed peaks at non-CS frequencies in 11/16 cases, likely reflecting normal variation in pre-training acoustic experiences. A stronger relationship was found between increased gamma power and the frequency with the strongest memory (peak of the difference between individual post- and pre-training FGGs) vs. behavioral responses to the CS training frequency. No such relationship was found for the theta/alpha band (4-15 Hz). These findings indicate that the strength of specific increased neuronal synchronization within primary sensory cortical fields can determine the specific contents of memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. 2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Xin-Juan Yang

    2013-08-01

    Full Text Available The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs. In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 2–12 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.

  19. Evaluation of the inhibition of carbohydrate hydrolysing enzymes, antioxidant activity and polyphenolic content of extracts of ten African Ficus species (Moraceae) used traditionally to treat diabetes.

    Science.gov (United States)

    Olaokun, Oyinlola O; McGaw, Lyndy J; Eloff, Jacobus N; Naidoo, Vinny

    2013-05-04

    Some Ficus species have been used in traditional African medicine in the treatment of diabetes. The antidiabetic potential of certain species has been confirmed in vivo but the mechanism of activity remains uncertain. The aim of this study was to determine the activity and to investigate the mechanism of antidiabetic activity of ten selected Ficus species through inhibition of α-amylase and α-glucosidase activity, and the possible relationship between these activities, the total polyphenolic content and the antioxidant activity. Dried acetone leaf extracts were reconstituted with appropriate solvents and used to determine total polyphenolic content antioxidant activity, α-amylase and α-glucosidase inhibitory activity. The crude acetone extract of F. lutea had the highest polyphenolic content (56.85 ± 1.82 mg GAE/g of dry material) and the strongest antioxidant activity with a TEAC value of 4.80 ± 0.90. The antioxidant activity of the acetone extracts of the Ficus species may not be ascribed to total polyphenolic content alone. The crude extract at a concentration of 0.5 mg/ml of F. lutea (64.3 ± 3.6%) had the best α-glucosidase (sucrase) inhibitory activity. The EC50 of F. lutea (290 ± 111 μg/ml) was not significantly different from that of F. sycomorus (217 ± 69 μg/ml). The α-amylase inhibitory activity of F. lutea (95.4 ± 1.2%) at a concentration of 1 mg/ml was the highest among the Ficus species screened. The EC50 for F. lutea (9.42 ± 2.01 μ g/ml), though the highest, was not significantly different (p < 0.05) from that of F. craterostoma and F. natalensis. It was apparent that the crude acetone extract of F. lutea is a partially non-competitive inhibitor of α-amylase and α-glucosidase. Based on correlation coefficients polyphenolics may be responsible for α-glucosidase activity but probably not for α-amylase activity. Antidiabetic activity potential via inhibition of α-amylase and α-glucosidase was

  20. Education is the strongest socio-economic predictor of smoking in pregnancy.

    Science.gov (United States)

    Härkönen, Juho; Lindberg, Matti; Karlsson, Linnea; Karlsson, Hasse; Scheinin, Noora M

    2018-01-14

    To investigate socio-economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions. Cross-sectional analysis with linked survey and register data. South-western Finland. A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study. The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire-based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio-economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated. Mother's education was the strongest socio-economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2-3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1-9.0; P education, 2.9 (95% CI = 1.4-6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P education and 14.4 (95% CI = 6.3-33.0; P education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1-3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4-2.8; P pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general). © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study

  1. Haemolytic activity within the species Fibrocapsa japonica (Raphidophyceae)

    NARCIS (Netherlands)

    de Boer, M. Karin; Tyl, Monika R.; Fu, Meng; Kulk, Gemma; Liebezeit, Gerd; Tomas, Carmelo R.; Lenzi, Allison; Naar, Jerome; Vrieling, Engel G.; van Rijssel, Marion

    Strong haemolytic activity was observed for extracts of 15 Fibrocapsa japonica strains collected from different global regions. The EC(50) values ranged between 0.4 x 10(4) and 1.9 x 10(4) F.japonica cells ml(-1).The relationship between the haemolytic activity observed in the cell extracts and the

  2. Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey

    Directory of Open Access Journals (Sweden)

    Osman Tuncay Agar

    2015-09-01

    Full Text Available Turkey is one of the most important centers of diversity for the genus Achillea L. in the world. Keeping in mind the immense medicinal importance of phenols, in this study, three species growing in Turkey, A. coarctata Poir. (AC, A. kotschyi Boiss. subsp. kotschyi (AK and A. lycaonica Boiss. & Heldr. (AL were evaluated for their phenolic compositions, total phenolic contents (TPC, antioxidant properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin, rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and 121.2 µg analyte/g extract, respectively. The findings exhibited a strong correlation between TPC and both free radical scavenging activity and total antioxidant capacity (TAC. Among studied species, the highest TPC (148.00 mg GAE/g extract and TAC (2.080 UAE, the strongest radical scavenging (EC50 = 32.63 μg/mL, the most prominent wound healing and most abundant cytotoxic activities were observed with AK. The results suggested that AK is a valuable source of flavonoids and chlorogenic acid with important antioxidant, wound healing and cytotoxic activities. These findings warrant further studies to assess the potential of AK as a bioactive source that could be exploited in pharmaceutical, cosmetics and food industries.

  3. Nematicidal activity of acetophenones and chalcones against Meloidogyne incognita and structure-activity considerations.

    Science.gov (United States)

    Caboni, Pierluigi; Aissani, Nadhem; Demurtas, Monica; Ntalli, Nikoletta; Onnis, Valentina

    2016-01-01

    With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita. The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC(50/24 h) values of 12 ± 5 and 15 ± 4 mg L(-1) respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC(50/24 h) 0.4 ± 0.3 mg L(-1)). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC(50/24 h) value 25 ± 17 mg L(-1)). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC(50/24) h value 26 ± 15 mg L(-1)) than 4-methoxyacetophenone (EC(50/24 h) value 43 ± 10 mg L(-1)). Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients. © 2015 Society of Chemical Industry.

  4. Antioxidant activities of extracts from areca (Areca catectu L.) flower ...

    African Journals Online (AJOL)

    The antioxidant activities of areca ( Areca catectu L.) flower, husk and seed extracts were evaluated using 3 complementary in vitro assays, inhibition of DPPH (1,1-diphenyl-2- picrylhydrazyl) radicals, inhibition of hydroxyl radicals and reducing power system. The EC50 values were calculated for all the methods in order to ...

  5. Correlation between activation of PPAR¿ and resistin downregulation in a mouse adipocyte cell line by a series of thiazolidinediones.

    NARCIS (Netherlands)

    Sotiriou, A.; Blaauw, R.H.; Meijer, C.; Gijsbers, L.H.; Burg, van der B.; Vervoort, J.; Rietjens, I.M.C.M.

    2013-01-01

    The present study shows significant correlations between the EC50 for PPAR¿ activation in a reporter gene cell line and resistin downregulation in mouse adipocytes, and between the IC50 for resistin downregulation and the already published minimum effective dose for antihyperglycemic activity in a

  6. Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular Activity of three antiviral drugs against bovine herpesviruses 1, 2 and 5 in cell culture

    Directory of Open Access Journals (Sweden)

    Renata Dezengrini

    2010-10-01

    Full Text Available A atividade de três fármacos antivirais (Aciclovir [ACV], Ganciclovir [GCV] e Foscarnet [PFA] foi testada in vitro frente aos herpesvírus bovino tipos 1 (BoHV-1, 2 (BoHV-2 e 5 (BoHV-5. Para isso, utilizou-se o teste de reducao de placas virais em cultivo celular, testando-se diferentes concentracoes dos farmacos frente a 100 doses infectantes para 50% dos cultivos celulares (DICC50 dos respectivos virus. Pelo teste de MTT (3-(4,5-Dimethylthiazol- 2-yl-2,5-diphenyltetrazolium bromide, verificou-se que concentracoes inferiores a 200ƒÊg/mL dos tres antivirais resultaram em indices de viabilidade de celulas MDBK e Hep2 superiores a 80%. Com base na concentracao citotoxica para 50% das celulas (CC50 e na concentracao dos farmacos efetiva para inibir em 50% o numero de placas virais (EC50, calculou-se o indice de seletividade (IS dos antivirais para os tres herpesvirus. Assim, o ACV demonstrou ser moderadamente ativo frente ao BoHV-1 (EC50: 112,9ƒÊg/mL e IS: 4,5, ao BoHV-2 (EC50: 114,2 ƒÊg/mL e IS: 4,5 e BoHV-5 (EC50: 96,9ƒÊg/mL e IS: 5,3. O GCV apresentou atividade moderada frente ao BoHV-2 (EC50: 33,5ƒÊg/mL e IS: 16,6 e, em menor grau, contra o BoHV-5 (EC50: 123,2ƒÊg/mL e IS: 4,5, sendo ineficaz frente ao BoHV-1 (EC50: 335,8ƒÊg/mL e IS: 1,7. O PFA apresentou atividade antiviral mais pronunciada, sendo o unico farmaco que, na concentracao de 100ƒÊg/mL, inibiu completamente a producao de placas pelos tres virus testados. O PFA foi o mais efetivo in vitro frente ao BoHV-1 (EC50: 29,5ƒÊg/mL e IS: 42,2, ao BoHV-2 (EC50: 45,2ƒÊg/mL e IS: 27,6 e ao BoHV-5 (EC50: 7,8ƒÊg/mL e IS: 160,6. Portanto, os resultados obtidos indicam que o PFA pode se constituir em um candidato para terapia experimental de infeccoes pelos herpesvirus de bovinos in vivo.The activity of three anti-herpetic drugs (Acyclovir [ACV], Gancyclovir [GCV] and Foscarnet [PFA] was tested against bovine herpesvirus 1 (BoHV-1, 2 (BoHV-2 and 5 (BoHV-5 in vitro using the

  7. Antileishmanial and immunomodulatory activity of Xylopia discreta.

    Science.gov (United States)

    López, R; Cuca, L E; Delgado, G

    2009-10-01

    This study aimed at determining the in vitro antileishmanial activity of the essential oil and eight extracts obtained from Xylopia discreta. J774 and U937 macrophages were exposed to the different substances to establish the median lethal concentration (LC(50)). The median effective concentration (EC(50)) was obtained by determining the reduction of Leishmania panamensis-infected cells. A selectivity index (SI) (LC(50)/EC(50)) >or= 20 defined a specific activity for one Xylopia discreta leaf extracts and for the essential oil, being these the two that showed the highest activity (SI = 64.8 and 110, respectively in J774 cells). To assess the substances' immunomodulatory activity, pro- and anti-inflammatory soluble mediators produced after treating infected macrophages were quantified by flow cytometry. The leaf methanol extract and the essential oil induced a differential production of monocyte chemoattractant protein-1, a chemokine associated with a Leishmania-resistant phenotype (Th1).

  8. Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study

    Science.gov (United States)

    Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

    2017-01-01

    Objectives: The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. Materials and Methods: ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. Results: ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC50) of ACh in the presence of atropine (10−6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC50of ACh alone. The EC50of 5-HT in the presence of ketanserin (10−5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC50of 5-HT alone. Similarly, the EC50of histamine in the presence of pheniramine maleate (10−6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC50of histamine alone. Conclusion: From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims. PMID:28458421

  9. Nematicidal activity of mint aqueous extracts against the root-knot nematode Meloidogyne incognita.

    Science.gov (United States)

    Caboni, Pierluigi; Saba, Marco; Tocco, Graziella; Casu, Laura; Murgia, Antonio; Maxia, Andrea; Menkissoglu-Spiroudi, Urania; Ntalli, Nikoletta

    2013-10-16

    The nematicidal activity and chemical characterization of aqueous extracts and essential oils of three mint species, namely, Mentha × piperita , Mentha spicata , and Mentha pulegium , were investigated. The phytochemical analysis of the essential oils was performed by means of GC-MS, whereas the aqueous extracts were analyzed by LC-MS. The most abundant terpenes were isomenthone, menthone, menthol, pulegone, and carvone, and the water extracts yielded mainly chlorogenic acid, salvianolic acid B, luteolin-7-O-rutinoside, and rosmarinic acid. The water extracts exhibited significant nematicidal activity against Meloidogyne incognita , and the EC50/72h values were calculated at 1005, 745, and 300 mg/L for M. × piperita, M. pulegium, and M. spicata, respectively. Only the essential oil from M. spicata showed a nematicidal activity with an EC50/72h of 358 mg/L. Interestingly, menthofuran and carvone showed EC50/48h values of 127 and 730 mg/L, respectively. On the other hand, salicylic acid, isolated in the aqueous extracts, exhibited EC50 values at 24 and 48 h of 298 ± 92 and 288 ± 79 mg/L, respectively.

  10. Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study.

    Science.gov (United States)

    Brechmann, Thorsten; Sperlbaum, Andre; Schmiegel, Wolff

    2017-02-07

    To identify a set of contributors, and weight and rank them on a pathophysiological basis. Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth (SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways (impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ 2 test, Student's t -test and logistic regression models. A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier (gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance (any resecting gastric surgery OR = 2.6, any colonic resection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors (any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism (hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus (OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or IgA-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model (OR = 3.0). The most important contributors for the development of SIBO in ascending

  11. Docking and Antiherpetic Activity of 2-Aminobenzo[de]-isoquinoline-1,3-diones

    Directory of Open Access Journals (Sweden)

    Rashad Al-Salahi

    2015-03-01

    Full Text Available As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The new series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones was examined against HSV-1 and HSV-2 using a cytopathic effect inhibition assay. In terms of effective concentration (EC50, furaldehyde, thiophene aldehyde and allyl isothiocyanide derivatives 14‒16 showed potent activity against HSV-1 (EC50 = 19.6, 16.2 and 17.8 μg/mL, compared to acyclovir as a reference drug (EC50 = 1.8 μg/mL. Moreover, 14 and 15 were found to exhibit valuable activity against HSV-2. Many of the tested compounds demonstrated weak to moderate EC50 values relative to their inactive parent compound (2-amino-1H-benzo[de]isoquinoline-1,3-dione, while compounds 7, 9, 13, 14, 15, 16, 21 and 22 were the most active set of antiviral compounds throughout this study. The cytotoxicity (CC50, EC50, and the selectivity index (SI values were determined. In a molecular docking study, the ligand-receptor interactions of compounds 1–24 and their parent with the HSV-1 thymidine kinase active site were investigated using the Molegro Virtual Docker (MVD software. Based on the potent anti-HSV properties of the previous naphthalimide condensate products, further exploration of this series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones is warranted.

  12. An Active Insect Kinin Analog with 4-Aminopyroglutamate, A Novel cis-Peptide Bond, Type VI beta-Turn Motif

    Science.gov (United States)

    2004-01-01

    Kinin Analogs in the Cricket Acheta domesticus Peptidomimetic Analog Stimulation of Malpighian Tubule Fluid Secretion-EC50 (10 7M) (% maximal...Malpighian tubule fluid secretion in the cricket, Acheta domesticus . Active Insect Kinin Analog with Type VI Turn-Mimic 4-Aminopyroglutamate 415 zole moiety

  13. Do nonphysical punishments reduce antisocial behavior more than spanking? a comparison using the strongest previous causal evidence against spanking

    Directory of Open Access Journals (Sweden)

    Cox Ronald B

    2010-02-01

    Full Text Available Abstract Background The strongest causal evidence that customary spanking increases antisocial behavior is based on prospective studies that control statistically for initial antisocial differences. None of those studies have investigated alternative disciplinary tactics that parents could use instead of spanking, however. Further, the small effects in those studies could be artifactual due to residual confounding, reflecting child effects on the frequency of all disciplinary tactics. This study re-analyzes the strongest causal evidence against customary spanking and uses these same methods to determine whether alternative disciplinary tactics are more effective in reducing antisocial behavior. Methods This study re-analyzed a study by Straus et al.1 on spanking and antisocial behavior using a sample of 785 children who were 6 to 9 years old in the 1988 cohort of the American National Longitudinal Survey of Youth. The comprehensiveness and reliability of the covariate measure of initial antisocial behavior were varied to test for residual confounding. All analyses were repeated for grounding, privilege removal, and sending children to their room, and for psychotherapy. To account for covarying use of disciplinary tactics, the analyses were redone first for the 73% who had reported using at least one discipline tactic and second by controlling for usage of other disciplinary tactics and psychotherapy. Results The apparently adverse effect of spanking on antisocial behavior was replicated using the original trichotomous covariate for initial antisocial behavior. A similar pattern of adverse effects was shown for grounding and psychotherapy and partially for the other two disciplinary tactics. All of these effects became non-significant after controlling for latent comprehensive measures of externalizing behavior problems. Conclusions These results are consistent with residual confounding, a statistical artifact that makes all corrective actions by

  14. Perception and the strongest sensory memory trace of multi-stable displays both form shortly after the stimulus onset.

    Science.gov (United States)

    Pastukhov, Alexander

    2016-02-01

    We investigated the relation between perception and sensory memory of multi-stable structure-from-motion displays. The latter is an implicit visual memory that reflects a recent history of perceptual dominance and influences only the initial perception of multi-stable displays. First, we established the earliest time point when the direction of an illusory rotation can be reversed after the display onset (29-114 ms). Because our display manipulation did not bias perception towards a specific direction of illusory rotation but only signaled the change in motion, this means that the perceptual dominance was established no later than 29-114 ms after the stimulus onset. Second, we used orientation-selectivity of sensory memory to establish which display orientation produced the strongest memory trace and when this orientation was presented during the preceding prime interval (80-140 ms). Surprisingly, both estimates point towards the time interval immediately after the display onset, indicating that both perception and sensory memory form at approximately the same time. This suggests a tighter integration between perception and sensory memory than previously thought, warrants a reconsideration of its role in visual perception, and indicates that sensory memory could be a unique behavioral correlate of the earlier perceptual inference that can be studied post hoc.

  15. The 100 strongest radio point sources in the field of the Large Magellanic Cloud at 1.4 GHz

    Directory of Open Access Journals (Sweden)

    Payne J.L.

    2009-01-01

    Full Text Available We present the 100 strongest 1.4 GHz point sources from a new mosaic image in the direction of the Large Magellanic Cloud (LMC. The observations making up the mosaic were made using Australia Telescope Compact Array (ATCA over a ten year period and were combined with Parkes single dish data at 1.4 GHz to complete the image for short spacing. An initial list of co-identifications within 1000 at 0.843, 4.8 and 8.6 GHz consisted of 2682 sources. Elimination of extended objects and artifact noise allowed the creation of a refined list containing 1988 point sources. Most of these are presumed to be background objects seen through the LMC; a small portion may represent compact H ii regions, young SNRs and radio planetary nebulae. For the 1988 point sources we find a preliminary average spectral index (α of -0.53 and present a 1.4 GHz image showing source location in the direction of the LMC.

  16. The 100 Strongest Radio Point Sources in the Field of the Large Magellanic Cloud at 1.4 GHz

    Directory of Open Access Journals (Sweden)

    Payne, J. L.

    2009-06-01

    Full Text Available We present the 100 strongest 1.4~GHz point sources from a new mosaicimage in the direction of the Large Magellanic Cloud (LMC. The observationsmaking up the mosaic were made using Australia Telescope Compact Array (ATCAover a ten year period and were combined with Parkes single dish data at 1.4 GHz to complete the image for short spacing. An initial list of co-identifications within 10arcsec at 0.843, 4.8 and 8.6 GHz consisted of 2682 sources. Elimination of extended objects and artifact noise allowed the creation of a refined list containing 1988 point sources. Most of these are presumed to be background objects seen through the LMC; a small portion may represent compact HII regions, young SNRs and radio planetary nebulae. For the 1988 point sources we find a preliminary average spectral index ($alpha$ of -0.53 and present a 1.4 GHz image showing source locationin the direction of the LMC.

  17. Evidence for the strongest version of the 4d a-theorem via a-maximization along RG flows

    International Nuclear Information System (INIS)

    Barnes, Edwin; Intriligator, Ken; Wecht, Brian; Wright, Jason

    2004-01-01

    In earlier work, we (KI and BW) gave a two line 'almost proof' (for supersymmetric RG flows) of the weakest form of the conjectured 4d a-theorem, that aIRaUV, using our result that the exact superconformal R-symmetry of 4d SCFTs maximizes a=3TrR3-TrR. The proof was incomplete because of two identified loopholes: theories with accidental symmetries, and the fact that it is only a local maximum of a. Here we discuss and extend a proposal of Kutasov (which helps close the latter loophole) in which a-maximization is generalized away from the endpoints of the RG flow, with Lagrange multipliers that are conjectured to be identified with the running coupling constants. a-maximization then yields a monotonically decreasing 'a-function' along the RG flow to the IR. As we discuss, this proposal in fact suggests the strongest version of the a-theorem: that 4d RG flows are gradient flows of an a-function, with positive-definite metric. In the perturbative limit, the RG flow metric thus obtained is shown to agree precisely with that found by very different computations by Osborn and collaborators. As examples, we discuss a new class of 4d SCFTs, along with their dual descriptions and IR phases, obtained from SQCD by coupling some of the flavors to added singlets

  18. The Strongest Acceleration of >40 keV Electrons by ICME-driven Shocks at 1 au

    Science.gov (United States)

    Yang, Liu; Wang, Linghua; Li, Gang; Wimmer-Schweingruber, Robert F.; He, Jiansen; Tu, Chuanyi; Tian, Hui; Bale, Stuart D.

    2018-01-01

    We present two case studies of the in-situ electron acceleration during the 2000 February 11 shock and the 2004 July 22 shock, with the strongest electron flux enhancement at 40 keV across the shock, among all the quasi-perpendicular and quasi-parallel ICME-driven shocks observed by the WIND 3DP instrument from 1995 through 2014 at 1 au. We find that for this quasi-perpendicular (quasi-parallel) shock on 2000 February 11 (2004 July 22), the shocked electron differential fluxes at ∼0.4–50 keV in the downstream generally fit well to a double-power-law spectrum, J ∼ E ‑β , with an index of β ∼ 3.15 (4.0) at energies below a break at ∼3 keV (∼1 keV) and β ∼ 2.65 (2.6) at energies above. For both shock events, the downstream electron spectral indices appear to be similar for all pitch angles, which are significantly larger than the index prediction by diffusive shock acceleration. In addition, the downstream electron pitch-angle distributions show the anisotropic beams in the anti-sunward-traveling direction, while the ratio of the downstream over ambient fluxes appears to peak near 90° pitch angles, at all energies of ∼0.4–50 keV. These results suggest that in both shocks, shock drift acceleration likely plays an important role in accelerating electrons in situ at 1 au. Such ICME-driven shocks could contribute to the formation of solar wind halo electrons at energies ≲2 keV, as well as the production of solar wind superhalo electrons at energies ≳2 keV in interplanetary space.

  19. Antioxidant Activity of the Essential Oil and Methanolic Extract of Teucrium orientale (L.) subsp. taylori (Boiss.) Rech. f.

    Science.gov (United States)

    Amiri, Hamzeh

    2010-01-01

    This study was designed to examine the chemical composition and in-vitro antioxidant activity of the essential oil and methanolic extract of Teucrium orientale subsp. taylori. The GC and GC–MS analysis of the essential oil resulted in determination of 40 components representing 96.4% of the oil. The major constituents of the oil were linalool (28.6%), caryophyllene oxide (15.6%), 1,8-cineol (4.5%), β-pinene (8.7%), 3-octanol (9.5%), β-caryophyllene (7.3%), and germacrene-D (4.1%). Antioxidant activities of the samples were determined by two different tests, namely DPPH and β-carotene- linoleic acid assay. In DPPH system, the weakest radical scavenging activity was exhibited by the non-polar sub fraction of methanolic extract (237.40 ± 2.1 μg/mL). Antioxidant activity of the polar sub fraction of methanolic extract was superior to all samples tested, showing an EC50 value of 61.45 ± 0.5 μg/ mL. The inhibition capacity (%) of the polar sub fraction of methanolic extract (95.21% ± 1.3) was found to be the strongest and almost equal to the inhibition capacity of the positive control BHT (94.9% ± 1.1). The amount of the total phenolics was the highest in the polar subfraction, i.e. 370 μg/mg of the dry extract (37%). A positive correlation was observed between the antioxidant activity and the total phenolics of the extracts. PMID:24381607

  20. Antioxidant Activity of the Essential Oil and Methanolic Extract of Teucrium orientale (L.) subsp. taylori (Boiss.) Rech. f.

    Science.gov (United States)

    Amiri, Hamzeh

    2010-01-01

    This study was designed to examine the chemical composition and in-vitro antioxidant activity of the essential oil and methanolic extract of Teucrium orientale subsp. taylori. The GC and GC-MS analysis of the essential oil resulted in determination of 40 components representing 96.4% of the oil. The major constituents of the oil were linalool (28.6%), caryophyllene oxide (15.6%), 1,8-cineol (4.5%), β-pinene (8.7%), 3-octanol (9.5%), β-caryophyllene (7.3%), and germacrene-D (4.1%). Antioxidant activities of the samples were determined by two different tests, namely DPPH and β-carotene- linoleic acid assay. In DPPH system, the weakest radical scavenging activity was exhibited by the non-polar sub fraction of methanolic extract (237.40 ± 2.1 μg/mL). Antioxidant activity of the polar sub fraction of methanolic extract was superior to all samples tested, showing an EC50 value of 61.45 ± 0.5 μg/ mL. The inhibition capacity (%) of the polar sub fraction of methanolic extract (95.21% ± 1.3) was found to be the strongest and almost equal to the inhibition capacity of the positive control BHT (94.9% ± 1.1). The amount of the total phenolics was the highest in the polar subfraction, i.e. 370 μg/mg of the dry extract (37%). A positive correlation was observed between the antioxidant activity and the total phenolics of the extracts.

  1. Hemoglobin to Hematocrit Ratio: The Strongest Predictor of Femoral Head Osteonecrosis in Children With Sickle Cell Disease.

    Science.gov (United States)

    Worrall, Douglas; Smith-Whitley, Kim; Wells, Lawrence

    2016-03-01

    Femoral head osteonecrosis (ON) secondary to sickle cell disease (SCD) often progresses to femoral head collapse, requiring total hip arthroplasty. However, this treatment has a limited durability and patients with SCD have higher rates of complications, requiring multiple revision operations. Identifying risk factors linked to ON in SCD can facilitate earlier precollapse diagnosis and surgical treatment aimed at preservation of the native hip joint. Fifty-nine children treated at our institution between January 2001 and April 2012 with SCD and ON, as diagnosed by magnetic resonance imaging or radiographic imaging, were compared with age-matched and sickle cell phenotype-matched (SS, SC, Sβ, Sβ) controls with no evidence of ON. Two sided t-tests assuming unequal variances determined statistically risk factors and threshold values were assigned to calculate odds ratios. Systolic blood pressure (P=1.2×10, OR=3.68), diastolic blood pressure (P=0.0084, OR=1.41), weight in the SCD-SS population (P=0.04, OR=1.85), and hemoglobin (Hb) in the SCD-SS population (P=0.036, OR=2.56) were elevated in cases. Curiously, dividing the Hb by the hematocrit to serve as a clinical proxy for the mean corpuscular Hb concentration (MCHC) produced an excellent predictor of ON (P=2.06×10, OR=5.17), which was especially pronounced in the SCD-SS subpopulation (P=2.28×10, OR=8.65). Among children with SCD, the overall prevalence of ON was 9% (59/658) and the phenotype with the highest prevalence of ON was Sβ thalassemia with an ON prevalence of 11.1%. There was no observed correlation between ON and height, body mass index, cholesterol, mean corpuscular volume, hematocrit, or glucocorticoid use. These data support a novel clinical marker, the MCHC proxy, as the strongest predictor of ON in children with SCD. High-risk children should receive hip magnetic resonance imaging to diagnose early ON and facilitate interventions focused on hip preservation, forestalling, or possibly preventing

  2. Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity.

    Science.gov (United States)

    Sauerberg, Per; Pettersson, Ingrid; Jeppesen, Lone; Bury, Paul S; Mogensen, John P; Wassermann, Karsten; Brand, Christian L; Sturis, Jeppe; Wöldike, Helle F; Fleckner, Jan; Andersen, Anne-Sofie T; Mortensen, Steen B; Svensson, L Anders; Rasmussen, Hanne B; Lehmann, Søren V; Polivka, Zdenek; Sindelar, Karel; Panajotova, Vladimira; Ynddal, Lars; Wulff, Erik M

    2002-02-14

    Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.

  3. Total phenolics and antioxidant activity of five medicinal plant

    International Nuclear Information System (INIS)

    Sousa, Cleyton Marcos de M.; Silva, Hilris Rocha e; Vieira-Junior, Gerardo Magela; Ayres, Mariane Cruz C.; Costa, Charllyton Luis S. da; Araajo, Delton Servulo; Cavalcante, Luis Carlos D.; Barros, Elcio Daniel S.; Araujo, Paulo Breitner de M.; Brandao, Marcela S.; Chaves, Mariana H.

    2007-01-01

    This paper describes total phenolics content and antioxidant activity in the ethanolic extract of leaves, bark and roots of five medicinal plants: Terminalia brasiliensis Camb., Terminalia fagifolia Mart. and Zucc., Copernicia cerifera (Miller) H.E. Moore, Cenostigma macrophyllum Tul. var. acuminata Teles Freire and Qualea grandiflora Mart. The total phenolics content of the plant extracts, determined by the Folin-Ciocalteu method, varied from 250.0 ±8,2 to 763,63 ±13.03 mg of gallic acid equivalent/g dry EtOH extract. The antioxidant activity of extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay system. Extract of bark from T. brasiliensis, the most active, with an EC 50 value of 27.59 ± 0.82 μg/mL, was comparable to rutin (EC 50 = 27.80 ± 1.38) and gallic acid (EC 50 = 24.27 ± 0.31), used as positive controls. The relationship between total phenolic content and antioxidant activity was positive and significant for T. brasiliensis, C. macrophyllum and C. cerifera. (author)

  4. Novel Phenolic Inhibitors of Small/Intermediate-Conductance Ca(2+)-Activated K(+) Channels, KCa3.1 and KCa2.3

    DEFF Research Database (Denmark)

    Olivan-Viguera, Aida; Valero, Marta Sofía; Murillo, María Divina

    2013-01-01

    . The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM), followed by mesalamine (EC50≥10 µM). The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyl)oxymethyl]phenyl]methyl 3...... in fibrotic and inflamed tissues and some tumors rendering the channel a potential drug target. In the present study, we searched for novel potent small molecule inhibitors of KCa3.1 by testing a series of 20 selected natural and synthetic (poly)phenols, synthetic benzoic acids, and non-steroidal anti......-inflammatory drugs (NSAIDs), with known cytoprotective, anti-inflammatory, and/or cytostatic activities. METHODOLOGYPRINCIPAL FINDINGS: In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM) and resveratrol (EC50 10 µM) as KCa3.1 inhibitors with moderate potency...

  5. The 9.2 ka event in Asian summer monsoon area: the strongest millennial scale collapse of the monsoon during the Holocene

    Science.gov (United States)

    Zhang, Wenchao; Yan, Hong; Dodson, John; Cheng, Peng; Liu, Chengcheng; Li, Jianyong; Lu, Fengyan; Zhou, Weijian; An, Zhisheng

    2018-04-01

    Numerous Holocene paleo-proxy records exhibit a series of centennial-millennial scale rapid climatic events. Unlike the widely acknowledged 8.2 ka climate anomaly, the likelihood of a significant climate excursion at around 9.2 cal ka BP, which has been notably recognized in some studies, remains to be fully clarified in terms of its magnitude and intensity, as well as its characteristics and spatial distributions in a range of paleoclimatic records. In this study, a peat sediment profile from the Dajiuhu Basin in central China was collected with several geochemical proxies and a pollen analysis carried out to help improve understanding of the climate changes around 9.2 cal ka BP. The results show that the peat development was interrupted abruptly at around 9.2 cal ka BP, when the chemical weathering strength decreased and the tree-pollen declined. This suggests that a strong drier regional climatic event occurred at around 9.2 cal ka BP in central China, which was, in turn, probably connected to the rapid 9.2 ka climate event co-developing worldwide. In addition, based on the synthesis of our peat records and the other Holocene hydrological records from Asian summer monsoon (ASM) region, we further found that the 9.2 ka event probably constituted the strongest abrupt collapse of the Asian monsoon system during the full Holocene interval. The correlations between ASM and the atmospheric 14C production rate, the North Atlantic drift ice records and Greenland temperature indicated that the weakened ASM event at around 9.2 cal ka BP could be interpreted by the co-influence of external and internal factors, related to the changes of the solar activity and the Atlantic Meridional Overturning Circulation (AMOC).

  6. The 9.2 ka event in Asian summer monsoon area: the strongest millennial scale collapse of the monsoon during the Holocene

    Science.gov (United States)

    Zhang, Wenchao; Yan, Hong; Dodson, John; Cheng, Peng; Liu, Chengcheng; Li, Jianyong; Lu, Fengyan; Zhou, Weijian; An, Zhisheng

    2017-06-01

    Numerous Holocene paleo-proxy records exhibit a series of centennial-millennial scale rapid climatic events. Unlike the widely acknowledged 8.2 ka climate anomaly, the likelihood of a significant climate excursion at around 9.2 cal ka BP, which has been notably recognized in some studies, remains to be fully clarified in terms of its magnitude and intensity, as well as its characteristics and spatial distributions in a range of paleoclimatic records. In this study, a peat sediment profile from the Dajiuhu Basin in central China was collected with several geochemical proxies and a pollen analysis carried out to help improve understanding of the climate changes around 9.2 cal ka BP. The results show that the peat development was interrupted abruptly at around 9.2 cal ka BP, when the chemical weathering strength decreased and the tree-pollen declined. This suggests that a strong drier regional climatic event occurred at around 9.2 cal ka BP in central China, which was, in turn, probably connected to the rapid 9.2 ka climate event co-developing worldwide. In addition, based on the synthesis of our peat records and the other Holocene hydrological records from Asian summer monsoon (ASM) region, we further found that the 9.2 ka event probably constituted the strongest abrupt collapse of the Asian monsoon system during the full Holocene interval. The correlations between ASM and the atmospheric 14C production rate, the North Atlantic drift ice records and Greenland temperature indicated that the weakened ASM event at around 9.2 cal ka BP could be interpreted by the co-influence of external and internal factors, related to the changes of the solar activity and the Atlantic Meridional Overturning Circulation (AMOC).

  7. Heart and/or soul : reality and fiction in the association between the two strongest contributors to the global burden of disease - ischemic heart disease and depression

    NARCIS (Netherlands)

    de Jonge, Peter

    Depression and heart disease are the strongest contributors to the global burden of disease and are often intertwined: depression is a risk factor for heart disease and vice versa. Moreover, depression in patients with established heart disease is associated with cardiovascular disease progression.

  8. "My Voice Is Definitely Strongest in Online Communities": Students Using Social Media for Queer and Disability Identity-Making

    Science.gov (United States)

    Miller, Ryan A.

    2017-01-01

    In this qualitative study I explored the social media activities of 25 lesbian, gay, bisexual, transgender, and queer students with disabilities at a research-intensive university. Using a framework of identity-making that accounts for students' reflections, narrations, and actions, I detail students' experiences exploring queer/ disability…

  9. Novel Series of Potent Glucokinase Activators Leading to the Discovery of AM-2394.

    Science.gov (United States)

    Dransfield, Paul J; Pattaropong, Vatee; Lai, Sujen; Fu, Zice; Kohn, Todd J; Du, Xiaohui; Cheng, Alan; Xiong, Yumei; Komorowski, Renee; Jin, Lixia; Conn, Marion; Tien, Eric; DeWolf, Walter E; Hinklin, Ronald J; Aicher, Thomas D; Kraser, Christopher F; Boyd, Steven A; Voegtli, Walter C; Condroski, Kevin R; Veniant-Ellison, Murielle; Medina, Julio C; Houze, Jonathan; Coward, Peter

    2016-07-14

    Glucokinase (GK) catalyzes the phosphorylation of glucose to glucose-6-phosphate. We present the structure-activity relationships leading to the discovery of AM-2394, a structurally distinct GKA. AM-2394 activates GK with an EC50 of 60 nM, increases the affinity of GK for glucose by approximately 10-fold, exhibits moderate clearance and good oral bioavailability in multiple animal models, and lowers glucose excursion following an oral glucose tolerance test in an ob/ob mouse model of diabetes.

  10. Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents

    Directory of Open Access Journals (Sweden)

    Pramod K. Sahu

    2017-07-01

    Full Text Available A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a exhibited the most potent anti-herpes simplex virus (HSV-1 (EC50 = 1.47 µM and HSV-2 (EC50 = 6.34 µM activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e–g exhibited significant anti-human cytomegalovirus (HCMV activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d.

  11. Activity of alkanediol alkanoates against pathogenic plant fungi Rhizoctonia solani and Sclerotium rolfsii.

    Science.gov (United States)

    Shukla, Paraj; Walia, Suresh; Ahluwalia, Vivek; Parmar, Balraj S; Nair, Muraleedharan G

    2012-09-01

    Thirty known dialkanoates of ethylene, propylene and diethylene glycols were synthesized by reacting the glycols with acyl chlorides and their structures confirmed by IR, NMR and mass spectral analyses. They exhibited significant antifungal activity against two phytopathogenic fungi Rhizoctonia solani Kuehn and Sclerotium rolfsii Sacc in a dose dependent manner. Propylene glycol dipentanoate was the most active against R. solani. followed by diethylene glycol dibutanoate and ethylene glycol dibutanoate. Against S. rolfsii ethylene glycol diheptanoate was found to be most active followed by diethylene glycol diisobutanoate As compared to the standard reference benomyl (EC50 5.16 microg/mL), the potential alkanediol dialkanoates showed EC50 in the range of 33 - 60 microg/mL.

  12. Evaluation of the antioxidant activity of extracts and flavonoids obtained from Bunium alpinum Waldst.

    Directory of Open Access Journals (Sweden)

    Lefahal Mostefa

    2017-03-01

    Full Text Available The aim of the present work was to evaluate the antioxidant activity of extracts and four flavonoids that had been isolated from the aerial parts of Bunium alpinum Waldst. et Kit. (Apiaceae and Tamarix gallica L. (Tamaricaceae. In this work, the four flavonoids were first extracted via various solvents, then purified through column chromatography (CC and thin layer chromatography (TLC. The four compounds were subsequently identified by spectroscopic methods, including: UV, mass spectrum 1H NMR and 13C NMR. The EtOAc extract of Bunium alpinum Waldst. et Kit yielded quercetin-3-O-β-glucoside (3’,4’,5,7-Tetrahydroxyflavone-3-β-D-glucopyranoside (1, while the EtOAc and n-BuOH extracts of Tamarix gallica L. afforded 3,5,3’-trihydroxy-7,4’-dimethoxyflavone (2, 3,5,7-trihydroxy-4’-methoxyflavone (3 and 5-hydroxy-3,7,4’-trimethoxyflavone (4. The antioxidant activity of the extracts and the flavonoids were then evaluated through DPPH free radical-scavenging assay. Of all studied extracts, the n-Butanol extract of Bunium alpinum (EC50 = 1.84 μg/ml showed the best antioxidant activity against (DPPH. In contrast, the isolates demonstrated varying degrees of antioxidant activity: compound (1 was the more active (EC50 = 0.28 μg/ml, followed by compound (3 and (2 (EC50 = 0.309μg/ml, EC50 = 0.406 μg/ml, respectively, compound (4 showed the lowest activity. All the isolated flavonoids exhibited antioxidant activity, but this was lower than the control (Trolox. In conclusion, due to the presence of flavonoids in their ariel parts, the studied plants could be natural sources of several important antioxidant agents

  13. Secondary metabolites from Vietnamese marine invertebrates with activity against Trypanosoma brucei and T. cruzi.

    Science.gov (United States)

    Thao, Nguyen Phuong; No, Joo Hwan; Luyen, Bui Thi Thuy; Yang, Gyongseon; Byun, Soo Young; Goo, Junghyun; Kim, Kyung Tae; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Van Minh, Chau; Schmidt, Thomas J; Kang, Jong Seong; Kim, Young Ho

    2014-06-11

    Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM). Laevigatol B (1) and 5α-cholest-8(14)-ene-3β,7α-diol (5) exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  14. Synthesis, Antifungal Activity and QSAR of Some Novel Carboxylic Acid Amides

    Directory of Open Access Journals (Sweden)

    Shijie Du

    2015-03-01

    Full Text Available A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-ylphenyl-2-(trifluoromethylbenzamide (3c exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 µg/mL and Rhizoctonia solani (EC50 = 19.19 µg/mL, compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 µg/mL, respectively. Comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173.

  15. Chemical Constituents and Antioxidant Activity of fresh leaves of psidium guajava cultivated in pakistan

    International Nuclear Information System (INIS)

    Begum, S.; Ali, S.N.; Tauseef, S.

    2014-01-01

    The in vitro antioxidant activities of the methanol extract of fresh leaves of Psidium guajava cultivated in Pakistan and its different fractions were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. The methanol extract, main ethyl acetate fraction and its polar sub fraction showed high free radical scavenging activity with EC50 11.72, 11.72 and 46.8 micro g/mL respectively. The first two values are comparable with that of reference compound ascorbic acid (EC50 9.4 ?g/mL). The known antioxidants gallic acid (1), methyl ferulate (2) and methyl p-E-coumarate (3) were isolated from the ethyl acetate insoluble fraction. Their structures were identified by mass, 1H- and 13C-NMR spectroscopy. Compounds 2 and 3 are reported for the first time from the genus Psidium. (author)

  16. Isocyanides Derived from α,α-Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment.

    Science.gov (United States)

    Inoue, Yuki; Takashima, Shuhei; Nogata, Yasuyuki; Yoshimura, Erina; Chiba, Kazuhiro; Kitano, Yoshikazu

    2018-03-01

    Herein, we contribute to the development of environmentally friendly antifoulants by synthesizing eighteen isocyanides derived from α,α-disubstituted amino acids and evaluating their antifouling activity/toxicity against the cypris larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good antifouling activity without significant toxicity and exhibited EC 50 values of 0.07 - 7.30 μg/mL after 120-h exposure. The lowest EC 50 values were observed for valine-, methionine-, and phenylalanine-derived isocyanides, which achieved > 95% cypris larvae settlement inhibition at concentrations of less than 30 μg/mL without exhibiting significant toxicity. Thus, the prepared isocyanides should be useful for further research focused on the development of environmentally friendly antifouling agents. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  17. Usability Testing of Guided Internet-based Parent Training for Challenging Behavior in Children with Fetal Alcohol Spectrum Disorder (Strongest Families FASD).

    Science.gov (United States)

    Hundert, Amos S; Huguet, Anna; Green, Courtney R; Hewitt, Amy J; Mushquash, Christopher J; Muhajarine, Nazeem; Sourander, Andre; Caughey, Heather; Lingley-Pottie, Patricia; McGrath, Patrick J; Reynolds, James N

    2016-01-01

    In order to meet the need for accessible interventions and support for families affected by fetal alcohol spectrum disorder (FASD), we have developed an Internet-based, distance intervention for caregivers of children with FASD between the ages of four and twelve, called Strongest Families™ FASD. To evaluate the usability of the Strongest Families FASD program content and website in terms of learnability, efficiency and acceptability. A remote usability testing approach was conducted in two iterative cycles of participants. Synchronous online usability testing sessions were conducted, followed by asynchronous testing. A total of 18 participants were included, comprised of both health care professionals with expertise in FASD and caregivers of children with FASD. The data collected in each cycle was examined for commonalities and results were used to inform changes to the website and content after each cycle. Participants rated the website as appealing and relatively easy and fast to use. Nevertheless, several usability problems were identified such as difficulty navigating between sections of content on the website, displaying too much content per page, and the relevance and appropriateness of the content as it related to FASD. The identification of usability problems was an important step in refining the Strongest Families FASD program before its effectiveness is evaluated in a randomized controlled trial.

  18. Remote population-based intervention for disruptive behavior at age four: study protocol for a randomized trial of Internet-assisted parent training (Strongest Families Finland-Canada).

    Science.gov (United States)

    McGrath, Patrick J; Sourander, Andre; Lingley-Pottie, Patricia; Ristkari, Terja; Cunningham, Charles; Huttunen, Jukka; Filbert, Katharine; Aromaa, Minna; Corkum, Penny; Hinkka-Yli-Salomäki, Susanna; Kinnunen, Malin; Lampi, Katja; Penttinen, Anne; Sinokki, Atte; Unruh, Anita; Vuorio, Jenni; Watters, Carolyn

    2013-10-21

    Oppositional Defiant Disorder (ODD) is characterized by angry and noncompliant behaviour. It is the most common disruptive behaviour disorder (DBD), with prevalence estimates of 6-9% for preschoolers and is closely linked to several long-term difficulties, including disorders of conduct, mood, anxiety, impulse-control, and substance abuse. ODD in children is related to parental depression, family dysfunction, and impairments in parental work performance. Children displaying early DBDs exhibit more symptoms of greater severity, more frequent offences, and commit more serious crimes later in life. The goal of the Strongest Families Finland Canada (SFFC) Smart Website intervention research program is to develop and evaluate an affordable, accessible, effective secondary prevention parent training program for disruptive behaviour in preschoolers to prevent the negative sequelae of ODD. Strongest Families is an 11-session program with two booster sessions that focuses on teaching skills to: strengthen parent-child relationships; reinforce positive behaviour; reduce conflict; manage daily transitions; plan for potentially problematic situations; promote emotional regulation and pro-social behaviour and decrease antisocial behaviour. This protocol paper describes an ongoing population-based randomized controlled trial (RCT) of high-risk 4 year-olds attending well-child clinics in Turku, Finland and environs to examine the effectiveness of the Strongest Families Smart Website intervention compared to an Education Control condition. Randomization consists of a 1:1 ratio for intervention versus the education group, stratified by the child's sex. The participants randomized to the intervention group receive access to the Strongest Families Smart Website and weekly telephone coaching sessions. The participants randomized to the Education Control condition receive access to a static website with parenting tips. Children are followed using parental and daycare teacher measures

  19. Synthesis and anthelmintic activity of arctigenin derivatives against Dactylogyrus intermedius in goldfish.

    Science.gov (United States)

    Hu, Yang; Liu, Lei; Liu, Guang-Lu; Tu, Xiao; Wang, Gao-Xue; Ling, Fei

    2017-08-01

    To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10mg/L. Compared to traditional drug praziquantel (EC 50 =2.69mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC 50 values of 2.48 and 1.52mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC 50 values of 2.13 and 2.07mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Antiviral activity of Petiveria alliacea against the bovine viral diarrhea virus.

    Science.gov (United States)

    Ruffa, M J; Perusina, M; Alfonso, V; Wagner, M L; Suriano, M; Vicente, C; Campos, R; Cavallaro, L

    2002-07-01

    Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. Antiviral activity of the infusions and methanolic extracts of Aristolochia macroura, Celtis spinosa, Plantago major, Schinus areira, Petiveria alliacea and four extracts obtained from the leaves and stems of the last plant were evaluated by the plaque assay. P. alliacea, unlike A. macroura, C. spinosa, P. major and S. areira, inhibited bovine viral diarrhea virus (BVDV) replication. Neither P. alliacea nor the assays of the other plants were active against herpes simplex virus type 1, poliovirus type 1, adenovirus serotype 7 and vesicular stomatitis virus type 1. Four extracts of P. alliacea were assayed to detect anti-BVDV activity. Ethyl acetate (EC(50) of 25 microg/ml) and dichloromethane (EC(50) of 43 microg/ml) extracts were active; moreover, promising SI (IC(50)/EC(50)) values were obtained. BVDV is highly prevalent in the cattle population, there are no antiviral compounds available; additionally, it is a viral model of the hepatitis C virus. For these reasons and in view of the results obtained, the isolation and characterization of the antiviral components present in the P. alliacea extracts is worth carrying out in the future. Copyright 2002 S. Karger AG, Basel

  1. Strongest magnet in the cosmos

    CERN Document Server

    Zane, S

    2003-01-01

    In November 1996 a NASA satellite called the Rossi X-ray Timing Explorer (RXTE) was monitoring a rare type of pulsar some 40 000 light-years from Earth. The star, called SGR 1806-20, is one of just four known 'soft gamma repeaters' - rotating neutron stars that periodically emit huge bursts of gamma rays. Now an international team of astrophysicists studying the RXTE data has found evidence for what is known as a magnetar - the most magnetic object in the universe. (U.K.)

  2. In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.

    Science.gov (United States)

    Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William

    2016-01-11

    Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Trypanocidal activity of organic extracts from the Brazilian and Spanish marine sponges

    Directory of Open Access Journals (Sweden)

    Jéssica Carreira de Paula

    Full Text Available Abstract Chagas' disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affect millions of people worldwide. The available drugs for treatment of this infection cause serious side effects and have variable efficacy, especially in the chronic phase of the disease. In this context, natural compounds have shown great potential for the discovery of new chemotherapies for the treatment of this infection and various other diseases. In present study, we evaluated the in vitro antiprotozoal activity of five species of Brazilian and Spanish marine sponges (Condrosia reniformes, Tethya rubra, Tethya ignis, Mycale angulosa and Dysidea avara against T. cruzi. By GC–MS data, we observed that in these extracts were present the major classes of the following compounds: hydrocarbons, terpenes, steroids and alcohols. The extracts showed activity against the three forms of this parasite and did not induce toxicity in mammalian cells. Better activities were observed with the extracts of marine sponges, C. reniformes (EC50 = 0.6 μg/ml, D. avara (EC50 = 1.1 μg/ml and M. angulosa (EC50 = 3.8 μg/ml, against trypomastigote forms. In intracellular amastigote forms, the extract of T. ignis showed IC50 of 7.2 μg/ml and SI of 24.65. On this basis, our results indicate that these extracts can be promising chemotherapeutic agents against T. cruzi.

  4. Cytotoxicity and antiviral activities of Asplenium nidus, Phaleria macrocarpa and Eleusine indica

    Science.gov (United States)

    Tahir, Mariya Mohd; Ibrahim, Nazlina; Yaacob, Wan Ahmad

    2014-09-01

    Three local medicinal plants namely Asplenium nidus (langsuyar), Eleusine indica (sambau) and Phaleria macrocarpa (mahkota dewa) were screened for the cytotoxicity and antiviral activities. Six plant extracts were prepared including the aqueous and methanol extracts from A. nidus leaf and root, aqueous extract from dried whole plant of E. indica and methanol extract from P. macrocarpa fruits. Cytotoxicity screening in Vero cell line by MTT assay showed that the CC50 values ranged from 15 to 60 mg/mL thus indicating the safety of the extracts even at high concentrations. Antiviral properties of the plant extracts were determined by plaque reduction assay. The EC50 concentrations were between 3.2 to 47 mg/mL. The selectivity indices (SI = CC50/EC50) of each tested extracts ranged from 4.3 to 63.25 indicating the usefulness of the extracts as potential antiviral agents.

  5. Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

    2015-09-01

    Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

  6. Evaluation of antiviral activity of South American plant extracts against herpes simplex virus type 1 and rabies virus.

    Science.gov (United States)

    Müller, Vanessa; Chávez, Juliana H; Reginatto, Flávio H; Zucolotto, Silvana M; Niero, Rivaldo; Navarro, Dionezine; Yunes, Rosendo A; Schenkel, Eloir P; Barardi, Célia R M; Zanetti, Carlos R; Simões, Cláudia M O

    2007-10-01

    This paper describes the screening of different South American plant extracts and fractions. Aqueous and organic extracts were prepared and tested for antiherpetic (HSV-1, KOS and 29R strains) and antirabies (PV strain) activities. The evaluation of the potential antiviral activity of these extracts was performed by using an MTT assay for HSV-1, and by a viral cytopathic effect (CPE) inhibitory method for rabies virus (RV). The results were expressed as 50% cytotoxicity (CC(50)) for MTT assay and 50% effective (EC(50)) concentrations for CPE, and with them it was possible to calculate the selectivity indices (SI = CC(50)/EC(50)) of each tested material. From the 18 extracts/fractions tested, six extracts and four fractions showed antiviral action. Ilex paraguariensis, Lafoensia pacari, Passiflora edulis, Rubus imperialis and Slonea guianensis showed values of SI > 7 against HSV-1 KOS and 29-R strains and Alamanda schottii showed a SI of 5.6 against RV, PV strain.

  7. Antioxidant activity from the leaf extracts of Jacaranda puberula Cham., Bignoniaceae, a Brazilian medicinal plant used for blood depuration

    Directory of Open Access Journals (Sweden)

    Paula Macedo Lessa dos Santos

    Full Text Available The antioxidant activity of leaf extracts from Jacaranda puberula Cham., Bignoniaceae, was assayed by the DPPH (2,2-diphenyl-1-picryl-hydrazyl free radical scavenging method. Three phytomedicines (F1, F2, and F3 used as blood depurative, were tested by the same method. The free radical scavenger potential was measured by the discoloration of the solution. The EC50 values from Gingko bilobaEGb 761® extract and rutin, used as antioxidant for medical purposes, were used as reference. The ethanol extract (EE, ethyl acetate (EA, butanol (EB, aqueous (EAq and the sample A (obtained from extract EB, showed lower EC50 values than other extracts and phytomedicines. The antioxidant activity (AA of the extracts was related with the presence of the polyphenol compounds such as verbascoside (1 and cis-caffeoyl aldehyde (2. These structures were determined by chemical and spectroscopic methods and comparison with literature data.

  8. The effect of glycine replacement with flexible ω-amino acids on the antimicrobial and haemolytic activity of an amphipathic cyclic heptapeptide

    DEFF Research Database (Denmark)

    Oddo, Alberto; Nyberg, Nils; Frimodt-Møller, Niels

    2015-01-01

    Although cyclic peptide structures are usually investigated as highly constrained scaffolds, cyclic antimicrobial peptides of natural origin often feature flexible residues. Hereby we report our findings concerning a structure-activity study conducted on a model sequence by replacing a glycine...... to study changes in conformation. Increments as high as 16-fold in antimicrobial activity (as effective as lipidation) and >2-fold in haemolytic EC50 values were observed. Interestingly, secondary structures can be stabilized by increasing, rather than decreasing, ring flexibility....

  9. Spasmogenic and spasmolytic activity of rind of Punica granatum Linn.

    Science.gov (United States)

    Ali, Niaz; Jamil, Ayesha; Shah, Syed Wadood Ali; Shah, Ismail; Ahmed, Ghayour

    2017-02-07

    Rind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range. Rind of Punica granatum was subjected to shade drying. Shade dried materials were pulverized using conventional grinder. Grinded materials were macerated in commercial grade methanol. The extract of rind of P. granatum was concentrated using a rotary evaporator. Rabbits' jejunal preparations were mounted in organ bath containing 10 ml Tyrode's solution, constantly aerated with carbogen gas. Pg. Cr was tested on spontaneous rabbits' jejunal preparations in concentrations 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml. Pg. Cr was also tested on KCl (80 mM)-induced contractions in rabbits' jejunal preparations. Since we observed spasmogenic activity for the first time, hence we also determined the effects of Pg. Cr in presence of atropine (0.03 μM). Pg. Cr was also tested in presence of 0.03 μM of loratadine HCl. Pg. Cr was also tested on barium chloride induced contractions. Calcium Concentration Response Curves (CCRCs) were constructed in the absence and presence of test samples of Pg. Cr in decalcified tissues to explore its possible mode of action. Acute toxicity screening was also performed to determine its safe dose range. Phytochemical screening revealed the presence of saponins, tannins, carbohydrates, proteins, flavonoids, saponins and steroids. However, Pg. Cr tested negative for alkaloids and triterpenoids. Pg. Cr was safe up to 100 mg/kg with its LD 50 = 1305 mg/kg. Its respective EC 50, in the absence and presence of atropine, were 9.7 ± 0.3 and 3.12 ± 0.45 mg/ml. In

  10. The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels

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    Veronika Matschke

    2016-12-01

    Full Text Available Background/Aims: Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases. Methods: Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.1 channels. Results: We show that currents carried by Kv7.1 (EC50 = 1.48 μM, Kv7.1/KCNE1 (EC50 = 4.9 μM, and Kv7.4 (EC50 = 0.148 μM are strongly enhanced by the compound, whereas Kv7.2, Kv7.2/Kv7.3, and Kv7.5 are not sensitive to Rottlerin. Studies on Kv7.1/KCNE1 mutants and in silico modelling indicate that Rottlerin binds to the R-L3-activator site. Rottlerin mediated activation of Kv7.1/KCNE1 channels might be a promising approach in long QT syndrome. As a proof of concept, we show that Rottlerin shortens cardiac repolarisation in iPSC-derived cardiomyocytes expressing Kv7.1.Conclusion: Rottlerin or an optimized derivative holds a potential as QT interval correcting drug.

  11. In Vitro and In Vivo Activities of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites.

    Science.gov (United States)

    Szajnman, Sergio H; Galaka, Tamila; Li, Zhu-Hong; Li, Catherine; Howell, Nathan M; Chao, María N; Striepen, Boris; Muralidharan, Vasant; Moreno, Silvia N J; Rodriguez, Juan B

    2017-02-01

    We tested a series of sulfur-containing linear bisphosphonates against Toxoplasma gondii, the etiologic agent of toxoplasmosis. The most potent compound (compound 22; 1-[(n-decylsulfonyl)ethyl]-1,1-bisphosphonic acid) is a sulfone-containing compound, which had a 50% effective concentration (EC 50 ) of 0.11 ± 0.02 μM against intracellular tachyzoites. The compound showed low toxicity when tested in tissue culture with a selectivity index of >2,000. Compound 22 also showed high activity in vivo in a toxoplasmosis mouse model. The compound inhibited the Toxoplasma farnesyl diphosphate synthase (TgFPPS), but the concentration needed to inhibit 50% of the enzymatic activity (IC 50 ) was higher than the concentration that inhibited 50% of growth. We tested compound 22 against two other apicomplexan parasites, Plasmodium falciparum (EC 50 of 0.6 ± 0.01 μM), the agent of malaria, and Cryptosporidium parvum (EC 50 of ∼65 μM), the agent of cryptosporidiosis. Our results suggest that compound 22 is an excellent novel compound that could lead to the development of potent agents against apicomplexan parasites. Copyright © 2017 American Society for Microbiology.

  12. Kinetic behaviour of DPPH radical scavenging activity of tomato waste extracts

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    Ćetković Gordana S.

    2012-01-01

    Full Text Available The kinetic behaviour of tomato waste extracts (obtained from six genotypes and standard antioxidant compounds (ascorbic and caffeic acid were investigated using 2,2-diphenyl-1-picrylhydrazyl radical test. Based on the time needed for the reaction to reach steady state, the investigated extracts show very slow (steady state ≥ 180 min antiradical behaviour, ascorbic acid act as rapid antioxidant (steady state < 5min while caffeic acid is rapidintermediate antioxidant (5 min < steady state < 20 min. The efficient concentrations at different kinetic times EC50,t were determined for all extracts, ascorbic and caffeic acid. EC50,t was used as a parameter to screen and compare antiradical activities of food extracts with slow kinetic action. Irrespective of the time considered, the comparison of the EC50,t for extracts showed that the DPPH radicals scavenging activity of extracts decreased in the order of O2 > Knjaz > Bačka > Saint Pierre > Rutgers > Novosadski niski. Tomato waste extracts showed very slow kinetic action, which is probably result of the different kinetic bevaviour of phenolic compounds, present in tomato waste, as well as other antioxidants (vitamins, carotenoids etc.

  13. Brazilian savanna fruits contain higher bioactive compounds content and higher antioxidant activity relative to the conventional red delicious apple.

    Science.gov (United States)

    Siqueira, Egle Machado de Almeida; Rosa, Fernanda Ribeiro; Fustinoni, Adriana Medeiros; de Sant'Ana, Lívia Pimentel; Arruda, Sandra Fernandes

    2013-01-01

    The bioactive compounds content and the antioxidant activity (AA) of twelve fruits native to the Cerrado were compared with the Red Delicious apple by means of the antiradical efficiency (using the 2,2-diphenyl-1-picrylhydrazil assay/DPPH), ferric reducing antioxidant power (FRAP) and the β-carotene/linoleic system. The antiradical efficiency (AE) and the kinetic parameters (Efficient concentration/EC50 and time needed to reach the steady state to EC50 concentration/TEC50) of the DPPH curve were also evaluated for comparison with the Trolox equivalent (TE) values. A strong, significant and positive correlation was observed between the TE and AE values, whereas a weak and negative correlation was observed between TE and EC50, suggesting that the values of AE and TE are more useful for the determination of antiradical activity in fruits than the widely used EC50. The total phenolic content found in the fruits corresponded positively to their antioxidant activity. The high content of bioactive compounds (flavanols, anthocyanins or vitamin C) relative to the apple values found in araticum, cagaita, cajuzinho, jurubeba, lobeira, magaba and tucum corresponded to the high antioxidant activity of these fruits. Flavanols and anthocyanins may be the main bioactive components in these Cerrado fruits. The daily consumption of at least seven of the twelve Cerrado fruits studied, particularly, araticum, cagaita, lobeira and tucum, may confer protection against oxidative stress, and thus, they may prevent chronic diseases and premature aging. The findings of this study should stimulate demand, consumption and cultivation of Cerrado fruits and result in sustainable development of the region where this biome dominates.

  14. Brazilian savanna fruits contain higher bioactive compounds content and higher antioxidant activity relative to the conventional red delicious apple.

    Directory of Open Access Journals (Sweden)

    Egle Machado de Almeida Siqueira

    Full Text Available The bioactive compounds content and the antioxidant activity (AA of twelve fruits native to the Cerrado were compared with the Red Delicious apple by means of the antiradical efficiency (using the 2,2-diphenyl-1-picrylhydrazil assay/DPPH, ferric reducing antioxidant power (FRAP and the β-carotene/linoleic system. The antiradical efficiency (AE and the kinetic parameters (Efficient concentration/EC50 and time needed to reach the steady state to EC50 concentration/TEC50 of the DPPH curve were also evaluated for comparison with the Trolox equivalent (TE values. A strong, significant and positive correlation was observed between the TE and AE values, whereas a weak and negative correlation was observed between TE and EC50, suggesting that the values of AE and TE are more useful for the determination of antiradical activity in fruits than the widely used EC50. The total phenolic content found in the fruits corresponded positively to their antioxidant activity. The high content of bioactive compounds (flavanols, anthocyanins or vitamin C relative to the apple values found in araticum, cagaita, cajuzinho, jurubeba, lobeira, magaba and tucum corresponded to the high antioxidant activity of these fruits. Flavanols and anthocyanins may be the main bioactive components in these Cerrado fruits. The daily consumption of at least seven of the twelve Cerrado fruits studied, particularly, araticum, cagaita, lobeira and tucum, may confer protection against oxidative stress, and thus, they may prevent chronic diseases and premature aging. The findings of this study should stimulate demand, consumption and cultivation of Cerrado fruits and result in sustainable development of the region where this biome dominates.

  15. Antiviral activity of benzotriazole derivatives. 5-[4-(Benzotriazol-2-yl)phenoxy]-2,2-dimethylpentanoic acids potently and selectively inhibit Coxsackie Virus B5.

    Science.gov (United States)

    Loddo, Roberta; Novelli, Federica; Sparatore, Anna; Tasso, Bruno; Tonelli, Michele; Boido, Vito; Sparatore, Fabio; Collu, Gabriella; Delogu, Ilenia; Giliberti, Gabriele; La Colla, Paolo

    2015-11-01

    A library of 64 benzotriazole derivatives (17 of which were [4-(benzotriazol-2-yl)phenoxy]alkanoic acids) were screened for antiviral activity against a panel of twelve DNA and RNA viruses. Twenty-six compounds (12 of which were [4-(benzotriazol-2-yl)phenoxy]alkanoic acids) displayed activity against one or more viruses. CVB-5, RSV, BVDV, Sb-1 and YFV were, in decreasing order, the more frequently and effectively affected viruses; DENV-2, WNV, HIV-1 and Reo-1 were only occasionally and modestly affected, while the remaining viruses were not affected by any of the tested compounds. Worth of note were compounds 33 and 35; the former for the activity against Sb-1 (EC50=7 μM) and the latter for the large spectrum of activity including six viruses with a mean EC50=12 μM. Even more interesting were the alkanoic acids 45-48 and 50-57 for their activity against RSV and/or CVB-5. In particular, compound 56 displayed a potent and selective activity against CVB-5 with EC50=0.15 μM and SI=100, thus representing a valuable hit compound for the development of antiviral agents for the treatment of human pathologies related to this virus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1.

    Science.gov (United States)

    Hassounah, Said A; Alikhani, Ahmad; Oliveira, Maureen; Bharaj, Simrat; Ibanescu, Ruxandra-Ilinca; Osman, Nathan; Xu, Hong-Tao; Brenner, Bluma G; Mesplède, Thibault; Wainberg, Mark A

    2017-12-01

    Animal models are essential to study novel antiretroviral drugs, resistance-associated mutations (RAMs), and treatment strategies. Bictegravir (BIC) is a novel potent integrase strand transfer inhibitor (INSTI) that has shown promising results against HIV-1 infection in vitro and in vivo and against clinical isolates with resistance against INSTIs. BIC has a higher genetic barrier to the development of resistance than two clinically approved INSTIs, termed raltegravir and elvitegravir. Another clinically approved INSTI, dolutegravir (DTG) also possesses a high genetic barrier to resistance, while a fourth compound, termed cabotegravir (CAB), is currently in late phases of clinical development. Here we report the susceptibilities of simian immunodeficiency virus (SIV) and HIV-1 integrase (IN) mutants containing various RAMs to BIC, CAB, and DTG. BIC potently inhibited SIV and HIV-1 in single cycle infection with 50% effective concentrations (EC 50 s) in the low nM range. In single cycle SIV infections, none of the E92Q, T97A, Y143R, or N155H substitutions had a significant effect on susceptibility to BIC (≤4-fold increase in EC 50 ), whereas G118R and R263K conferred ∼14-fold and ∼6-fold increases in EC 50 , respectively. In both single and multiple rounds of HIV-1 infections, BIC remained active against the Y143R, N155H, R263K, R263K/M50I, and R263K/E138K mutants (≤4-fold increase in EC 50 ). In multiple rounds of infection, the G140S/Q148H combination of substitutions decreased HIV-1 susceptibility to BIC 4.8-fold compared to 16.8- and 7.4-fold for CAB and DTG, respectively. BIC possesses an excellent resistance profile in regard to HIV and SIV and could be useful in nonhuman primate models of HIV infection. Copyright © 2017 American Society for Microbiology.

  17. Design of a novel cyclotide-based CXCR4 antagonist with anti-human immunodeficiency virus (HIV)-1 activity

    Science.gov (United States)

    Aboye, Teshome L.; Ha, Helen; Majumber, Subhabrata; Christ, Frauke; Debyser, Zeger; Shekhtman, Alexander; Neamati, Nouri; Camarero, Julio A.

    2012-01-01

    Herein, we report for the first time the design and synthesis of a novel cyclotide able to efficiently inhibit HIV-1 viral replication by selectively targeting cytokine receptor CXCR4. This was accomplished by grafting a series of topologically modified CVX15 based peptides onto the loop 6 of cyclotide MCoTI-I. The most active compound produced in this study was a potent CXCR4 antagonist (EC50 ≈ 20 nM) and an efficient HIV-1 cell-entry blocker (EC50 ≈ 2 nM). This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based anti-cancer and anti-HIV-1 therapeutics. PMID:23151033

  18. Quantitative structure-activity relationship (QSAR) study of toxicity of quaternary ammonium compounds on Chlorella pyrenoidosa and Scenedesmus quadricauda.

    Science.gov (United States)

    Jing, Guohua; Zhou, Zuoming; Zhuo, Jing

    2012-01-01

    The acute toxicity of 13 quaternary ammonium compounds (QACs) to Chlorella pyrenoidosa and Scenedesmus quadricauda was investigated in the present study. Significant inhibition on algae biomass was observed and 96 h EC(50)-value of 13 QACs was tested. Sixteen physicochemical and quantum chemical parameters of the QACs were calculated using the semi-empirical MOPAC AMI method. The multiple linear regression (MLR) was employed to derive the quantitative structure-activity relationship (QSAR) models, by which the calculated parameters were correlated to the toxicity of QACs on the two green algaes. Results showed that the alkyl chain lengths (CL) and total connectivity (T(Con)) were the main descriptors in governing the log (1/EC(50)) values of the QACs in the two QSAR models. The two models had high predictive ability and stability, and two parameters were proved to have the general applicability in QSAR study of QACs congeners. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening.

    Science.gov (United States)

    Lauria, Antonino; Abbate, Ilenia; Gentile, Carla; Angileri, Francesca; Martorana, Annamaria; Almerico, Anna Maria

    2013-04-25

    The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.

  20. Investigation on Antibacterial and Antioxidant Activities, Phenolic and Flavonoid Contents of Some Thai Edible Plants as an Alternative for Antibiotics

    Directory of Open Access Journals (Sweden)

    J. H. Lee

    2014-10-01

    Full Text Available This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime fruits and its leaves, Sesbania grandiflora L. (Agati sesbania leaves, Piper sarmentosum Roxb (Wild betal leaves, Curcuma domestica Valeton (Turmeric roots, Morinda citrifolia L. (Beach mulberry leaves, Cassia siamea britt (Siamea cassia leaves, and Cocos nucifera L. (Coconut peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, 135 μg/mL. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of 306 μg/mL and 183 μg/mL, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% (EC50 values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and 47

  1. Investigation on antibacterial and antioxidant activities, phenolic and flavonoid contents of some thai edible plants as an alternative for antibiotics.

    Science.gov (United States)

    Lee, J H; Cho, S; Paik, H D; Choi, C W; Nam, K T; Hwang, S G; Kim, S K

    2014-10-01

    This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime) fruits and its leaves, Sesbania grandiflora L. (Agati sesbania) leaves, Piper sarmentosum Roxb (Wild betal) leaves, Curcuma domestica Valeton (Turmeric) roots, Morinda citrifolia L. (Beach mulberry) leaves, Cassia siamea britt (Siamea cassia) leaves, and Cocos nucifera L. (Coconut) peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC) were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, 135 μg/mL. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of 306 μg/mL and 183 μg/mL, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% (EC50) values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and 47.8

  2. Structure-activity relationships of acetylcholine derivatives with Lucilia cuprina nicotinic acetylcholine receptor α1 and α2 subunits in chicken β2 subunit hybrid receptors in comparison with chicken nicotinic acetylcholine receptor α4/β2.

    Science.gov (United States)

    Dederer, H; Berger, M; Meyer, T; Werr, M; Ilg, T

    2013-04-01

    Insect nicotinic acetylcholine (ACh) receptors (nAChRs) are the targets of several insecticide classes. In the present study, we report the gene identification and cloning of nAChR α1 and α2 subunits (Lcα1 and Lcα2) from the sheep blowfly Lucilia cuprina. Xenopus oocytes voltage clamp experiments as hybrids with the chicken β2 nAChR (Ggβ2) subunit resulted in ACh-gated ion channels with distinct dose-response curves for Lcα1/Ggβ2 (effective concentration 50% [EC50 ] = 80 nM; nH  = 1.05), and Lcα2/Ggβ2 (EC50  = 5.37 μM, nH  = 1.46). The neonicotinoid imidacloprid was a potent agonist for the α-bungarotoxin-sensitive Lcα1/Ggβ2 (EC50 ∼ 20 nM), while the α-bungarotoxin-resistant Lcα2/Ggβ2 showed a 30-fold lower sensitivity to this insecticide (EC50  = 0.62 μM). Thirteen close derivatives of ACh were analysed in EC50 , Hill coefficient and maximum current (relative to ACh) determinations for Lcα1/Ggβ2 and Lcα2/Ggβ2 and the chicken Ggα4/Ggβ2 nAChRs, and comparisons relative to ACh allowed the definition of novel structure-activity and structure-selectivity relationships. In the case of N-ethyl-acetylcholine, the EC50 of the chicken Ggα4/Ggβ2 rose by a factor of 1000, while for both Lcα1/Ggβ2 and Lcα2/Ggβ2, potency remained unchanged. Further derivatives with insect nAChR selectivity potential were acetyl-α-methylcholine and trimethyl-(3-methoxy-3-oxopropyl)ammonium, followed by acetylhomocholine and trimethyl-(4-oxopentyl) ammonium. Our results may provide guidance for the identification or design of insect-specific nAChR agonists using structure-based or in silico methods. © 2013 Royal Entomological Society.

  3. Antipoliovirus Activity of the Organic Extract of Eupatorium buniifolium: Isolation of Euparin as an Active Compound

    Directory of Open Access Journals (Sweden)

    María Florencia Visintini Jaime

    2013-01-01

    Full Text Available The antiviral activity of the organic extract (OE of Eupatorium buniifolium against poliovirus type 1 was determined by in vitro assays with an effective concentration 50 (EC50 of 23.3 ± 3.3 µg/mL. Bioassay-guided fractionation of the OE allowed the isolation of an active principle that was identified by spectroscopic methods (1H- and 13C-NMR, EI-MS, UV, and IR spectroscopy as the benzofuran euparin. The plaque reduction assay in Vero cells was used to assess the antiviral activity of euparin against poliovirus types 1, 2, and 3 with EC50 values of 0.47, 0.12, and 0.15 µg/mL, respectively. Moreover, this compound showed high selectivity indexes of 284.9, 1068, and 854.7, respectively. In order to identify the mechanism by which euparin exerts its antiviral activity, the virucidal effect, the pretreatment of Vero cells, and the time of action on one viral replication cycle were evaluated. Results obtained demonstrated that euparin exerts its effect during the early events of the replication cycle, from the virus adsorption to cells up to the first twenty minutes after infection. This is the first report on the presence of euparin in E. buniifolium and its antiviral activity.

  4. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    Science.gov (United States)

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Development of a Broad-Spectrum Antiviral Agent with Activity ...

    African Journals Online (AJOL)

    72 h; 6 = ACV, 72 h; 7.5 ng/mL H9, 72 h;8.10 ng/mL. H9, 72 h). Anti-HCMV activity. H9 inhibited the production of pp65 in HCMV- infected Helf cell culture supernatant in a dose-dependent manner. EC50 of H9 (0.46 ng/ml) was greater than that of the standard ganciclovir. (GCV) group (0.68 ng/ml). As shown in Fig 3A,.

  6. Activity of Fluorine-Containing Analogues of WC-9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii.

    Science.gov (United States)

    Chao, María N; Li, Catherine; Storey, Melissa; Falcone, Bruno N; Szajnman, Sergio H; Bonesi, Sergio M; Docampo, Roberto; Moreno, Silvia N J; Rodriguez, Juan B

    2016-12-16

    Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells. Two fluorine-containing derivatives, the 3-(3-fluorophenoxy)- and 3-(4-fluorophenoxy)phenoxyethyl thiocyanates, exhibited half-maximal effective concentration (EC 50 ) values of 1.6 and 4.9 μm, respectively, against tachyzoites of T. gondii, whereas they showed similar potency to WC-9 against intracellular T. cruzi (EC 50 values of 5.4 and 5.7 μm, respectively). In addition, 2-[3- (phenoxy)phenoxyethylthio]ethyl-1,1-bisphosphonate, which is a hybrid inhibitor containing 3-phenoxyphenoxy and bisphosphonate groups, has activity against T. gondii proliferation at sub-micromolar levels (EC 50 =0.7 μm), which suggests a combined inhibitory effect of the two functional groups. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Passive dosing of pyrethroid insecticides to Daphnia magna: Expressing excess toxicity by chemical activity

    DEFF Research Database (Denmark)

    Nørgaard Schmidt, Stine; Gan, Jay; Kretschmann, A. C.

    2015-01-01

    ) Effective chemical activities resulting in 50% immobilisation (Ea50) will be estimated from pyrethroid EC50 values via the correlation of sub-cooled liquid solubility (S L, [mmol/L], representing a=1) and octanol to water partitioning ratios (Kow), (3) The excess toxicity observed for pyrethroids...... activity do pyrethroids exert their toxicity, and how similar are the effective chemical activities (Ea50) for different pyrethroids? (3) How much more toxic are pyrethroids relative to baseline toxicity? Toxicity experiments were conducted using passive dosing: Polydimethyl siloxane (PDMS) silicone...

  8. Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

    Directory of Open Access Journals (Sweden)

    Betancur-Galvis LA

    1999-01-01

    Full Text Available Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity and antiherpetic activity. MTT (Tetrazolium blue and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2. The 50% cytotoxic concentration (CC50 and the 50% inhibitory concentration of the viral effect (EC50 for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50. These species are good candidates for further activity-monitored fractionation to identify active principles.

  9. Double positivity for HPV-DNA/p16ink4ais the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

    Science.gov (United States)

    Mena, Marisa; Taberna, Miren; Tous, Sara; Marquez, Sandra; Clavero, Omar; Quiros, Beatriz; Lloveras, Belen; Alejo, Maria; Leon, Xavier; Quer, Miquel; Bagué, Silvia; Mesia, Ricard; Nogués, Julio; Gomà, Montserrat; Aguila, Anton; Bonfill, Teresa; Blazquez, Carmen; Guix, Marta; Hijano, Rafael; Torres, Montserrat; Holzinger, Dana; Pawlita, Michael; Pavon, Miguel Angel; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, Francesc Xavier; Alemany, Laia

    2018-03-01

    The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16 INK4a /pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16 INK4a , HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16 INK4a , respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16 INK4a showed strongest diagnostic accuracy and prognostic value. Double positivity for HPV-DNA/p16 INK4a , a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy.

    Science.gov (United States)

    Pintye, Jillian; Bacchetti, Peter; Teeraananchai, Sirinya; Kerr, Stephen; Prasitsuebsai, Wasana; Singtoroj, Thida; Kuncze, Karen; Louie, Alexander; Koss, Catherine A; Jin, Chengshi; Phung, Nhi; Horng, Howard; Sohn, Annette H; Gandhi, Monica

    2017-12-01

    Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir (LPV) levels on viremia among youth on second-line ART. We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/mL) at least 24 weeks after switch to LPV-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of LPV were measured through liquid chromatography/tandem mass spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models. Overall, 244 children met the inclusion criteria for the present analysis. Approximately half (55%) were boys and the median age 10 years [interquartile range (IQR) 7-13]; 40% were older than 11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146-547) cells/mm and median HIV-RNA level was 5.0 (IQR 4.3-5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1-5) hair samples were collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher LPV hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/mL adjusted odds ratio = 0.41 per doubling in hair concentration, 95% confidence interval: 0.29 to 0.58, P 1000 copies/mL, adjusted odds ratio = 0.54, 95% confidence interval: 0.45 to 0.65, P Hair concentrations predict viremia among children with HIV on second-line ART and could guide clinical decisions for this population.

  11. Novel phenolic inhibitors of small/intermediate-conductance Ca²⁺-activated K⁺ channels, KCa3.1 and KCa2.3.

    Directory of Open Access Journals (Sweden)

    Aida Oliván-Viguera

    Full Text Available BACKGROUND: KCa3.1 channels are calcium/calmodulin-regulated voltage-independent K(+ channels that produce membrane hyperpolarization and shape Ca(2+-signaling and thereby physiological functions in epithelia, blood vessels, and white and red blood cells. Up-regulation of KCa3.1 is evident in fibrotic and inflamed tissues and some tumors rendering the channel a potential drug target. In the present study, we searched for novel potent small molecule inhibitors of KCa3.1 by testing a series of 20 selected natural and synthetic (polyphenols, synthetic benzoic acids, and non-steroidal anti-inflammatory drugs (NSAIDs, with known cytoprotective, anti-inflammatory, and/or cytostatic activities. METHODOLOGY/PRINCIPAL FINDINGS: In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM and resveratrol (EC50 10 µM as KCa3.1 inhibitors with moderate potency. The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM, followed by mesalamine (EC50≥10 µM. The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyloxymethyl]phenyl]methyl 3-fluoro-4-hydroxy-benzoate, was identified as a potent mixed KCa2/3 channel inhibitor with an EC50 of 19 nM for KCa3.1 and 360 pM for KCa2.3, which affected KCa1.1 and Kv channels only at micromolar concentrations. The KCa3.1/KCa2-activator SKA-31 antagonized the 13b-blockade. In proliferation assays, 13b was not cytotoxic and reduced proliferation of 3T3 fibroblasts as well as caffeic acid. In isometric vessel myography, 13b increased contractions of porcine coronary arteries to serotonin and antagonized endothelium-derived hyperpolarization-mediated vasorelaxation to pharmacological KCa3.1/KCa2.3 activation. CONCLUSIONS/SIGNIFICANCE: We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel

  12. Potentiated virucidal activity of pomegranate rind extract (PRE and punicalagin against Herpes simplex virus (HSV when co-administered with zinc (II ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV.

    Directory of Open Access Journals (Sweden)

    David M J Houston

    Full Text Available There is a clinical need for new therapeutic products against Herpes simplex virus (HSV. The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE and co-administered zinc (II ions.PRE was used in conjunction with zinc (II salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit.Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1 a value comparable to aciclovir (EC50 = 0.18 μg mL-1; however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1, whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution.The potentiated virucidal activity of PRE by coadministered zinc (II has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores.

  13. Secondary Metabolites from Vietnamese Marine Invertebrates with Activity against Trypanosoma brucei and T. cruzi

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    Nguyen Phuong Thao

    2014-06-01

    Full Text Available Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL. Among the compounds isolated from these extracts, laevigatol B (1 from Lobophytum crassum and L. laevigatum, (24S-ergost-4-ene-3-one (2 from Sinularia dissecta, astropectenol A (3 from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4 from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM. Laevigatol B (1 and 5α-cholest-8(14-ene-3β,7α-diol (5 exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  14. Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

    KAUST Repository

    Li, Yong Xin

    2013-04-25

    Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

  15. Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.

    Science.gov (United States)

    Bernard, Angela; Lacroix, Céline; Cabiddu, Maria G; Neyts, Johan; Leyssen, Pieter; Pompei, Raffaello

    2015-04-01

    The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC50) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC50 = 0.6 µM) and 1524 (EC50 = 0.33 µM). Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs. © The Author(s) 2015.

  16. Summer Learning Loss: Why Its Effect Is Strongest among Low-Income Students and How It Can Be Combated. Information Capsule. Volume 1011

    Science.gov (United States)

    Blazer, Christie

    2011-01-01

    Summer vacation is one of the predominant causes of the achievement gap in America's schools. While middle- and higher-income children spend their summers engaged in activities and enrolled in programs that strengthen and reinforce learning, the vast majority of children in low-income communities have little or no access to such opportunities. By…

  17. Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)

    DEFF Research Database (Denmark)

    Baumann, Markus; Hussain, Mohammad Musarraf; Henne, Nina

    2017-01-01

    in loss of activity, introduction of bromine in position 1 on the naphth-2-ylmethyl moiety (R3) resulted in an EC50 of 61 μM (mixture of diastereoisomers) against wild-type CXCR4; thus, the antagonistic activity of these tripeptidomimetics seems to be amenable to optimization of the aromatic moiety......Here we report a series of close analogues of our recently published scaffold-based tripeptidomimetic CXCR4 antagonists, containing positively charged guanidino groups in R1 and R2, and an aromatic group in R3. While contraction/elongation of the guanidine carrying side chains (R1 and R2) resulted...

  18. Chemical constituents and antioxidant activity from leaves extracts of Terminalia fagifolia Mart. et Zucc

    International Nuclear Information System (INIS)

    Ayres, Mariane Cruz Costa; Chaves, Mariana H.; Rinaldo, Daniel; Vilegas, Wagner; Vieira Junior, Gerardo Magela

    2009-01-01

    Phytochemical investigation of ethanolic leaves extracts of T. fagifolia led to the isolation of (+)-catechin, sitosterol-3-O-β-D-glucopyranoside, α and β tocopherol, a mixture of lupeol, α and β-amyrin, sitosterol and a mixture of glucoside flavonoids (CP-13). The structures of these compounds were identified by 1 H and 13 C NMR spectral analysis and comparison with literature data. Absolute configuration of the catechin was determinate by circular dichroism. Antioxidant activity (EC 50 ), evaluated by 2,2-diphenyl-1-picrylhidrazyl (DPPH) assay system, decreased in the order: (+)-catechin > hydroalcoholic fraction > CP-13 > aqueous fraction > EtOH extract. (author)

  19. Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels

    Science.gov (United States)

    Goudet, Cyril; Ferrer, Tania; Galàn, Loipa; Artiles, Adriana; Batista, Cesar F V; Possani, Lourival D; Alvarez, Julio; Aneiros, Abel; Tytgat, Jan

    2001-01-01

    Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 μM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels. PMID:11704639

  20. Analysis of phenolic compounds and radical scavenging activity of Echinacea spp.

    Science.gov (United States)

    Pellati, Federica; Benvenuti, Stefania; Magro, Lara; Melegari, Michele; Soragni, Fabrizia

    2004-04-16

    The aim of this study was to set up and validate an RP-LC method with DAD-detection to quantify caffeic acid derivatives in various Echinacea spp. Samples were extracted with 80% methanol. The analyses were carried out on a Lichrospher RP-18 column (125 mm x 4 mm i.d., 5 microm), with a mobile phase gradient, which increases the acetonitrile level in a phosphoric acid solution (0.1%). The flow rate was 1.5 ml/min. Detection was set at 330 nm. This method allowed the identification and quantification of caftaric acid, chlorogenic acid, caffeic acid, cynarin, echinacoside and cichoric acid in Echinacea roots and derivatives. The total phenolic content was 10.49 mg/g for E. angustifolia, 17.83 mg/g for E. pallida and 23.23 mg/g for E. purpurea. Among Echinacea commercial herbal medicines, a certain variability in the concentrations of phenolic compounds was observed. The radical scavenging activity of Echinacea methanolic extracts was evaluated in vitro with a spectrophotometric method based on the reduction of an alcoholic 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical solution at 517 nm in the presence of a hydrogen donating antioxidant. As for pure compounds, echinacoside had the highest capacity to quench DPPH* radicals (EC50 = 6.6 microM), while caftaric acid had the lowest (EC50 = 20.5 microM). The average EC50 values for E. purpurea, E. pallida and E. angustifolia were 134, 167 and 231 microg/ml, respectively. The radical scavenging activity of Echinacea root extracts reflected their phenolic composition. The results indicate that Echinacea roots and derivatives are a good source of natural antioxidants and could be used to prevent free-radical-induced deleterious effects.

  1. Anti-herpes virus activities of bioactive fraction and isolated pure constituent of Mallotus peltatus: an ethnomedicine from Andaman Islands.

    Science.gov (United States)

    Bag, Paromita; Chattopadhyay, Debprasad; Mukherjee, Hemanta; Ojha, Durbadal; Mandal, Nilanjan; Sarkar, Mamta Chawla; Chatterjee, Tapan; Das, Gobardhan; Chakraborti, Sekhar

    2012-05-24

    Viral infections, particularly the infections caused by herpes simplex virus (HSV), represent one of the most serious public health concerns globally because of their devastating impact. The aim of this study was to evaluate the antiviral potential of methanolic crude extract of an ethnomedicine Mallotus peltatus, its active fraction and pure compound, against HSV-1 F and HSV-2 G. The cytotoxicity (CC(50), the concentration of 50% cellular toxicity), antiviral effective concentration (EC(50), the concentration required to achieve 50% protection against virus-induced cytopathic effect), plaque reduction and the selectivity index (SI, the ratio of CC(50) and EC(50)) was determined. Results showed that the crude methanolic extract of M. peltatus possessed weak anti-HSV activity. In contrast, the active fraction A and isolated ursolic acid from fraction A exhibited potent antiherpesvirus activity against both HSV-1 (EC(50)= 7.8 and 5.5 μg/ml; SI = 22.3 and 20) and HSV-2 (EC(50)= 8.2 and 5.8 μg/ml, and SI = 21.2 and 18.97). The fraction A and isolated ursolic acid (10 μg/ml) inhibited plaque formation of HSV-1 and HSV-2 at more than 80% levels, with a dose dependent antiviral activity, compared to acyclovir. The time response study revealed that the anti-HSV activity of fraction A and isolated ursolic acid is highest at 2-5 h post-infection. Moreover, the time kinetics study by indirect immunofluorescence assay showed a characteristic pattern of small foci of single fluorescent cells in fraction A- treated virus infected cells at 2 h and 4 h post-infection, suggesting drug inhibited viral dissemination. Further, the PCR study with infected cell cultures treated with fraction A and isolated ursolic acid at various time intervals, failed to show amplification at 48-72 h, like acyclovir treated HSV-infected cells. Moreover, fraction A or isolated ursolic acid showed no interaction in combination with acyclovir. This study revealed that bioactive fraction A and isolated

  2. Antioxidant and cytotoxic activities of Thai medicinal plants named Khaminkhruea: Arcangelisia flava, Coscinium blumeanum and Fibraurea tinctoria

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    Niwat Keawpradub

    2005-08-01

    Full Text Available The stems of Arcangelisia flava, Coscinium blumeanum and Fibraurea tinctoria, collectively known in southern Thailand as Khaminkhruea, were sequentially extracted with petroleum ether, chloroform, methanol, and boiling water to afford 12 crude extracts. All extracts have been assessed for antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl radical and cytotoxic activity against brine shrimp and human cancer cell line MCF-7 (breast adenocarcinoma. Methanol extract of A. flava (AFM, and methanol and chloroform extracts of C. blumeanum (CBM and CBC exhibited moderate antioxidant activity with EC50 values of 25-55 μg/ml. Chloroform extracts of A. flava (AFC and F. tinctoria (FTC, AFM, CBC and CBM showed pronounced cytotoxic activity against brine shrimp and MCF-7 cells with LC50 and IC50 values of 210-278 and 8-12 μg/ml, respectively. Bioassay-guided chemical investigation led to the isolation of berberine as a main compound of AFC, AFM, CBC and CBM. Palmatine and jatrorrhizine were found to be main alkaloids of FTC, and minor alkaloids of AFC, AFM, CBC and CBM. In addition, an ester triacontanyl caffeate was isolated for the first time from C. blumeanum (CBC. Chemical structures of the isolated compounds were determined by spectroscopic methods particularly NMR and mass spectrometry. Triacontanyl caffeate was mainly responsible for antioxidant activity of C. blumeanum with an EC50 value of 6.8 μg/ml. Jatrorrhizine possessed moderate antioxidant activity with an EC50 value of 98.0 μg/ml, whereas palmatine and berberine were found to be considerably less active (EC50 >100 μg/ml. The LC50 values of the four isolated compounds on brine shrimp were ranging from 37-206 μg/ml. The IC50 values of berberine, palmatine and jatrorrhizine against MCF-7 cells were in the range of 1-4 μg/ml. Triacontanyl caffeate was considerably less cytotoxic than the alkaloids with an IC50 value of 15.5 μg/ml.

  3. Anti-herpes virus activities of bioactive fraction and isolated pure constituent of Mallotus peltatus: an ethnomedicine from Andaman Islands

    Directory of Open Access Journals (Sweden)

    Bag Paromita

    2012-05-01

    Full Text Available Abstract Background Viral infections, particularly the infections caused by herpes simplex virus (HSV, represent one of the most serious public health concerns globally because of their devastating impact. The aim of this study was to evaluate the antiviral potential of methanolic crude extract of an ethnomedicine Mallotus peltatus, its active fraction and pure compound, against HSV-1 F and HSV-2 G. Result The cytotoxicity (CC50, the concentration of 50% cellular toxicity, antiviral effective concentration (EC50, the concentration required to achieve 50% protection against virus-induced cytopathic effect, plaque reduction and the selectivity index (SI, the ratio of CC50 and EC50 was determined. Results showed that the crude methanolic extract of M. peltatus possessed weak anti-HSV activity. In contrast, the active fraction A and isolated ursolic acid from fraction A exhibited potent antiherpesvirus activity against both HSV-1 (EC50 = 7.8 and 5.5 μg/ml; SI = 22.3 and 20 and HSV-2 (EC50 = 8.2 and 5.8 μg/ml, and SI = 21.2 and 18.97. The fraction A and isolated ursolic acid (10 μg/ml inhibited plaque formation of HSV-1 and HSV-2 at more than 80% levels, with a dose dependent antiviral activity, compared to acyclovir. The time response study revealed that the anti-HSV activity of fraction A and isolated ursolic acid is highest at 2–5 h post-infection. Moreover, the time kinetics study by indirect immunofluorescence assay showed a characteristic pattern of small foci of single fluorescent cells in fraction A- treated virus infected cells at 2 h and 4 h post-infection, suggesting drug inhibited viral dissemination. Further, the PCR study with infected cell cultures treated with fraction A and isolated ursolic acid at various time intervals, failed to show amplification at 48–72 h, like acyclovir treated HSV-infected cells. Moreover, fraction A or isolated ursolic acid showed no interaction in combination with

  4. Chemical constituents of the essential oil, antioxidant and antibacterial activities from Elettariopsis curtisii Baker.

    Directory of Open Access Journals (Sweden)

    Vanida Chairgulprasert

    2008-08-01

    Full Text Available Elettariopsis curtisii Baker, the culinary and medicinal herb, was investigated to elucidate its chemical constituents and determine antioxidant and antibacterial activities. The essential oil of E. curtisii was obtained by steam distillation of fresh rhizomes in a maximum yield of 0.63%. GC-MS data indicated the presence of six compounds, of which trans-2-decenal (78.03% was the principal constituent. The essential oils and also the hexane, dichloromethane and methanol extracts from the rhizomes and leaves were assessed for antioxidant and antibacterial activities. In an evaluation of antioxidant activity, the crude dichloromethane extract of the leaves exhibited the highest scavenging effect on the DPPH radicalwith an EC50 of 0.28+0.01 mg/mL. The leaf dichloromethane extract also had the highest total phenol concentration, (73.4+2.80 mg GA/g of extract whereas the crude methanol extract from the rhizomes had the highest reducing power with an EC50 of 2.07+0.06 mg/mL. In terms of antibacterial activity, the essential oil (distilled from either the leaves or the rhizomesdisplayed the highest inhibitory activity, with the same MID value of 1 mg/disc against 5 strains of bacteria, Bacillus subtilis,Escherichia coli, Staphylococcus aureus, Sarcina sp. and Pseudomonas aeruginosa.

  5. Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning

    International Nuclear Information System (INIS)

    Huang, C.-P.; Fang, W.-H.; Lin, L.-I.; Chiou, Robin Y.; Kan, L.-S.; Chi, N.-H.; Chen, Y.-R.; Lin, T.-Y.; Lin, S.-B.

    2008-01-01

    Cytotoxic alkyl hydroquinone compounds have been isolated from many plants. We previously isolated 3 structurally similar cytotoxic alkyl hydroquinone compounds from the sap of the lacquer tree Rhus succedanea L. belonging to the sumac family, which have a long history of medicinal use in Asia. Each has an unsaturated alkyl chain attached to the 2-position of a hydroquinone ring. One of these isolates, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)], being the most cytotoxic, was chosen for studying the anticancer mechanism of these compounds. We found that HQ17(3) was a topoisomerase (Topo) II poison. It irreversibly inhibited Topo IIα activity through the accumulation of Topo II-DNA cleavable complexes. A cell-based assay showed that HQ17(3) inhibited the growth of leukemia HL-60 cells with an EC 50 of 0.9 μM, inhibited the topoisomerase-II-deficient cells HL-60/MX2 with an EC 50 of 9.6 μM, and exerted no effect on peripheral blood mononuclear cells at concentrations up to 50 μM. These results suggest that Topo II is the cellular drug target. In HL-60 cells, HQ17(3) promptly inhibited DNA synthesis, induced chromosomal breakage, and led to cell death with an EC 50 about one-tenth that of hydroquinone. Pretreatment of the cells with N-acetylcysteine could not attenuate the cytotoxicity and DNA damage induced by HQ17(3). However, N-acetylcysteine did significantly reduce the cytotoxicity of hydroquinone. In F344 rats, intraperitoneal injection of HQ17(3) for 28 days induced no clinical signs of toxicity. These results indicated that HQ17(3) is a potential anticancer agent, and its structural features could be a model for anticancer drug design

  6. Bioactive Peptides from Cartilage Protein Hydrolysate of Spotless Smoothhound and Their Antioxidant Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Jing Tao

    2018-03-01

    Full Text Available In the experiment, crude proteins from spotless smoothhound (Mustelus griseus, cartilages were isolated by HCl-Guanidine buffer, and its hydrolysate was prepared using trypsin at pH 8.0, 40 °C with a total enzyme dose of 2.5%. Subsequently, three antioxidant peptides were purified from the hydrolysate using membrane ultrafiltration, anion-exchange chromatography, gel filtration chromatography, and reverse phase high-performance liquid chromatography. The amino acid sequences of isolated peptides were identified as Gly-Ala-Glu-Arg-Pro (MCPE-A; Gly-Glu-Arg-Glu-Ala-Asn-Val-Met (MCPE-B; and Ala-Glu-Val-Gly (MCPE-C with molecular weights of 528.57, 905.00, and 374.40 Da, respectively, using protein amino acid sequence analyzer and mass spectrum. MCPE-A, MCPE-B and MCPE-C exhibited good scavenging activities on 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH• (EC50 3.73, 1.87, and 2.30 mg/mL, respectively, hydroxyl radicals (HO• (EC50 0.25, 0.34, and 0.06 mg/mL, respectively, 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radicals (ABTS+• (EC50 0.10, 0.05, and 0.07 mg/mL, respectively and superoxide anion radicals ( O 2 − • (EC50 0.09, 0.33, and 0.18 mg/mL, respectively. MCPE-B showed similar inhibiting ability on lipid peroxidation with butylated hydroxytoluene (BHT in a linoleic acid model system. Furthermore, MCPE-A, MCPE-B, and MCPE-C could protect H2O2-induced HepG2 cells from oxidative stress by decreasing the content of malonaldehyde (MDA and increasing the levels of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px, and glutathione reductase (GSH-Rx. Glu, Gly, Met, and Pro in their sequences and low molecular weight could be attributed to the antioxidant activities of three isolated peptides. These results suggested that GAERP (MCPE-A, GEREANVM (MCPE-B, and AEVG (MCPE-C from cartilage protein hydrolysate of spotless smoothhound might serve as potential antioxidants and be used in the pharmaceutical and

  7. Antitumour activity of Angelica archangelica leaf extract.

    Science.gov (United States)

    Sigurdsson, Steinthor; Ogmundsdottir, Helga M; Hallgrimsson, Jonas; Gudbjarnason, Sigmundur

    2005-01-01

    The purpose of this study was to examine the effect of a leaf extract from A. archangelica on the growth of Crl mouse breast cancer cells in vitro and in vivo. The antiproliferative activity of the extract was measured by 3H-thymidine uptake in the Crl cells in vitro. Twenty mice were injected with the Crl cells, and 11 of them were fed A. archangelica leaf extract, and the progress of the tumours was followed. The leaf extract was mildly antiproliferative on the Crl cells with an EC50 of 87.6 microg/ml The antitumour activity of the extract was expressed in the mice by marked reduction in tumour growth. In the experimental animals, 9 out of 11 mice developed no or very small tumours, whereas control animals, not receiving the extract, developed significantly larger tumours (parchangelica

  8. Activity of andrographolide against chikungunya virus infection.

    Science.gov (United States)

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R

    2015-09-18

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent.

  9. Structural characterization and evaluation of antioxidant, anticancer and hypoglycemic activity of radiation degraded oat (Avena sativa) β- glucan

    Science.gov (United States)

    Hussain, Peerzada R.; Rather, Sarver A.; Suradkar, Prashant P.

    2018-03-01

    Oat β-D-glucan after extraction was degraded at doses of 3, 6, 9, 12 and 15 kGy. The average molecular weight decreased to 45 kDa at dose of 15 kGy from an initial value of 200 kDa in native sample. XRD analysis revealed no significant change in diffraction pattern of irradiated samples when compared with control, except a decrease in intensity of x-ray diffraction. The results of the antioxidant activity revealed decrease in EC50 values and corresponding increase in antioxidant activity of radiation degraded oat β-D-glucan. Results of the anticancer studies indicated that cytotoxicity of gamma irradiated oat β-D-glucan in cancer cell lines was highest against colo-205 and MCF7 cancer cells compared to T47D cell and no cytotoxicity was observed in normal cell lines at all concentrations used. Evaluation of hypoglycemic activity showed highest inhibition in α-glucosidase activity compared to α-amylase activity due to gamma irradiation of oat β-D-glucan. Comparison of the EC50 values of known standards and gamma irradiated oat beta-glucan samples indicates that radiation treatment significantly modified the biological activity of the beta-glucan samples. Therefore, it is suggested that gamma irradiation can be used for producing low molecular weight oat β-D-glucan; which can help in modifying the biological activities.

  10. Synthesis, algal inhibition activities and QSAR studies of novel gramine compounds containing ester functional groups

    Science.gov (United States)

    Li, Xia; Yu, Liangmin; Jiang, Xiaohui; Xia, Shuwei; Zhao, Haizhou

    2009-05-01

    2,5,6-Tribromo-1-methylgramine (TBG), isolated from bryozoan Zoobotryon pellucidum was shown to be very efficient in preventing recruitment of larval settlement. In order to improve the compatibility of TBG and its analogues with other ingredients in antifouling paints, structural modification of TBG was focused mainly on halogen substitution and N-substitution. Two halogen-substitute gramines and their derivatives which contain ester functional groups at N-position of gramines were synthesized. Algal inhibition activities of the synthesized compounds against algae Nitzschia closterium were evaluated and the Median Effective Concentration (EC50) range was 1.06-6.74 μg ml-1. Compounds that had a long chain ester group exhibited extremely high antifouling activity. Quantitive Structure Activity Relationship (QSAR) studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors and biological activity of the synthesized compounds. The results show that the toxicity (log (1/EC50)) is correlated well with the partition coefficient log P. Thus, these products have potential function as antifouling agents.

  11. Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

    Science.gov (United States)

    Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

    2012-08-01

    Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643)

    DEFF Research Database (Denmark)

    Hansen, Rie Schultz; Diness, Thomas Goldin; Christ, Torsten

    2005-01-01

    increased both steady-state and tail current at all voltages tested. The EC(50) value for HERG channel activation was 10.5 microM. These results were reproduced on HERG channels expressed in mammalian human embryonic kidney 293 cells. In guinea pig cardiomyocytes, studied by patch clamp, application of 10......-a-go-go-related gene (ERG) potassium channels. We have developed the diphenylurea compound 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) and tested whether this small organic molecule could increase the activity of human ERG (HERG) channels expressed heterologously. In Xenopus laevis oocytes, NS1643...

  13. Synthesis and structure-activity studies on acidic amino acids and related diacids as NMDA receptor ligands

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B

    1994-01-01

    ]CPP-binding assay (IC50 = 7 +/- 3 microM) and electropharmacologically in the rat cortical wedge model (EC50 = 8 +/- 2 microM). In contrast to this, the tertbutyl analogue 7a of AMAA turned out to be an antagonist at NMDA and AMPA receptors. The conformational characteristics of AMAA and 7a, c were studied...... by molecular mechanics calculations. Compound 7a possesses extra steric bulk and shows significant restriction of conformational flexibility compared to AMAA and 7c, which may be determining factors for the observed differences in biological activity. Although the nitrogen atom of quinolinic acid (6) has very...

  14. Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

    Directory of Open Access Journals (Sweden)

    Shah Ismail

    2011-10-01

    Full Text Available Abstract Background Callistemon citrinus Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of Callistemon citrinus were reported to have relaxant (antispasmodic activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it. Methods The crude methanol extract was obtained by maceration with distilled water (500 ml three times and fractionated successively with n-hexane, chloroform, ethyl acetate and n-butanol (300 ml of each solvent. Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift. Results Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD50 value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4 mg/ml. Similarly, EC50 value for brine shrimp

  15. Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

    Science.gov (United States)

    2011-01-01

    Background Callistemon citrinus Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of Callistemon citrinus were reported to have relaxant (antispasmodic) activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it. Methods The crude methanol extract was obtained by maceration with distilled water (500 ml) three times and fractionated successively with n-hexane, chloroform, ethyl acetate and n-butanol (300 ml of each solvent). Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM) -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift. Results Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD50 value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4) mg/ml. Similarly, EC50 value for brine shrimp cytotoxicity is 65.5

  16. Antioxidant and DNA Damage Protecting Activity of Exopolysaccharides from the Endophytic Bacterium Bacillus cereus SZ1

    Directory of Open Access Journals (Sweden)

    Li Ping Zheng

    2016-02-01

    Full Text Available An endophytic bacterium was isolated from the Chinese medicinal plant Artemisia annua L. The phylogenetic and physiological characterization indicated that the isolate, strain SZ-1, was Bacillus cereus. The endophyte could produce an exopolysaccharide (EPS at 46 mg/L. The 1,1-diphenyl-2-picrylhydracyl (DPPH radical scavenging activity of the EPS reached more than 50% at 3–5 mg/mL. The EPS was also effective in scavenging superoxide radical in a concentration dependent fashion with an EC50 value of 2.6 mg/mL. The corresponding EC50 for scavenging hydroxyl radical was 3.1 mg/mL. Moreover, phenanthroline-copper complex-mediated chemiluminescent emission of DNA damage was both inhibited and delayed by EPS. The EPS at 0.7–1.7 mg/mL also protected supercoiled DNA strands in plasmid pBR322 against scission induced by Fenton-mediated hydroxyl radical. The preincubation of PC12 cells with the EPS prior to H2O2 exposure increased the cell survival and glutathione (GSH level and catalase (CAT activities, and decreased the level of malondialdehyde (MDA and lactate dehydrogenase (LDH activity in a dose-dependent manner, suggesting a pronounced protective effect against H2O2-induced cytotoxicity. Our study indicated that the EPS could be useful for preventing oxidative DNA damage and cellular oxidation in pharmaceutical and food industries.

  17. Nematicidal activity of 2-thiophenecarboxaldehyde and methylisothiocyanate from caper (Capparis spinosa) against Meloidogyne incognita.

    Science.gov (United States)

    Caboni, Pierluigi; Sarais, Giorgia; Aissani, Nadhem; Tocco, Graziella; Sasanelli, Nicola; Liori, Barbara; Carta, Annarosa; Angioni, Alberto

    2012-08-01

    New pesticides based on plant extracts have recently gained interest in the development of nontoxic crop protection chemicals. Numerous research studies are focused on the isolation and identification of new active compounds derived from plants. In this manuscript we report about the use of the Mediterranean species Capparis spinosa as a potent natural nematicidal agent against the root knot nematodes Meloidogyne incognita. Leaves, stems, and caper buds of Capparis spinosa were used to obtain their methanol extracts (LME, SME, BME) that were successively in vitro tested against second stage nematode juveniles (J2). In terms of paralysis induction, the methanol extract of the stem part (SME) was found more effective against M. incognita and then the caper methanol buds and leaves extracts. The chemical composition analysis of the extracts carried out by GC/MS and LC/MS techniques showed that methylisothiocyanate was the main compound of SME. The EC50 for SME after 3 days of immersion was 215 ± 36 mg/L. The constituent components of SME such as 2-thiophenecarboxaldehyde and methylisothiocyanate were successively in vitro tested for their nematicidal activity against J2. Both compounds induced paralysis on root knot nematodes ranking first (EC50 = 7.9 ± 1.6, and 14.1 ± 1.9 mg/L respectively) for M. incognita. Moreover, 2-thiophenecarboxaldehyde showed a strong fumigant activity.

  18. Indoline Amide Glucosides from Portulaca oleracea: Isolation, Structure, and DPPH Radical Scavenging Activity.

    Science.gov (United States)

    Jiao, Ze-Zhao; Yue, Su; Sun, Hong-Xiang; Jin, Tian-Yun; Wang, Hai-Na; Zhu, Rong-Xiu; Xiang, Lan

    2015-11-25

    A polyamide column chromatography method using an aqueous ammonia mobile phase was developed for large-scale accumulation of water-soluble indoline amide glucosides from a medicinal plant, Portulaca oleracea. Ten new [oleraceins H, I, K, L, N, O, P, Q, R, S (1-10)] and four known [oleraceins A-D (11-14)] indoline amide glucosides were further purified and structurally characterized by various chromatographic and spectroscopic methods. The DPPH radical scavenging activities of oleraceins K (5) and L (6), with EC50 values of 15.30 and 16.13 μM, respectively, were twice that of a natural antioxidant, vitamin C; the EC50 values of the 12 other indoline amides, which ranged from 29.05 to 43.52 μM, were similar to that of vitamin C. Structure-activity relationships indicated that the DPPH radical scavenging activities of these indoline amides correlate with the numbers and positions of the phenolic hydroxy groups.

  19. Anti-HIV activities of the compounds isolated from Polygonum cuspidatum and Polygonum multiflorum.

    Science.gov (United States)

    Lin, Hong-Wei; Sun, Ming-Xue; Wang, Yun-Hua; Yang, Liu-Meng; Yang, Ying-Ruo; Huang, Ning; Xuan, Li-Jiang; Xu, Ya-Ming; Bai, Dong-Lu; Zheng, Yong-Tang; Xiao, Kai

    2010-06-01

    The 70 % EtOH extract of Polygonum cuspidatum showed inhibitory action against HIV-1-induced syncytium formation at non-cytotoxic concentrations in vitro with a 50 % effective concentration (EC(50)) of 13.94 +/- 3.41 microg/mL. Through bioactivity-guided fractionation, 20 phenolic compounds, including eight stilbenoids, were isolated from the roots of Polygonum cuspidatum, and their anti-HIV-1 activities were evaluated. Results showed that compounds 1, 13, 14, and 16 demonstrated fairly strong antiviral activity against HIV-1-induced cytopathic effects in C8166 lymphocytes at non-cytotoxic concentrations, with EC (50) values of 4.37 +/- 1.96 microg/mL, 19.97 +/- 5.09, 14.4 +/- 1.34 microg/mL, and 11.29 +/- 6.26 microg/mL and therapeutic index (TI) values of 8.12, > 10.02, > 13.89, and > 17.71, respectively. Other compounds showed either weak or no effects. Compound 6 also showed weak inhibition (153.42 +/- 19.25 microg/mL); however, it possesses very good water solubility and showed almost no cytotoxicity (> 2000 microg/mL), therefore achieving a fairly good TI (13.04). The activities of the two compounds (3 and 18) from Polygonum multiflorum were also assayed. The relationship between molecular structures and their bioactivities was also discussed. Georg Thieme Verlag KG Stuttgart-New York.

  20. Phytochemistry, cytotoxicity and antiviral activity of Eleusine indica (sambau)

    Science.gov (United States)

    Iberahim, Rashidah; Yaacob, Wan Ahmad; Ibrahim, Nazlina

    2015-09-01

    Goose grass also known as Eleusine indica (EI) is a local medicinal plant that displays antioxidant, antimicrobial and anticancer activities. The present study is to determine the phytochemical constituents, cytotoxicity and antiviral activities for both crude extract and fraction obtained from the plant. The crude extract contained more secondary metabolites compared to the hexane fraction as gauged using standard phytochemical tests. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract and hexane fraction were 2.07 and 5.62 mg/ml respectively. The antiviral activity towards Herpes Simplex Virus type 1 (HSV-1) was determined using plaque reduction assay. The selective indices (SI = CC50 / EC50) for both methanol extract and hexane fraction were 12.2 and 6.2 respectively. These results demonstrate that the extract prepared from E. indica possesses phytochemical compound that was non cytotoxic to the cell with potential antiviral activity.

  1. Antiviral Activity, Pharmacokinetics, and Safety of BMS-488043, a Novel Oral Small-Molecule HIV-1 Attachment Inhibitor, in HIV-1-Infected Subjects ▿

    Science.gov (United States)

    Hanna, George J.; Lalezari, Jacob; Hellinger, James A.; Wohl, David A.; Nettles, Richard; Persson, Anna; Krystal, Mark; Lin, Pinfang; Colonno, Richard; Grasela, Dennis M.

    2011-01-01

    BMS-488043 is a novel and unique oral small-molecule inhibitor of the attachment of human immunodeficiency virus type 1 (HIV-1) to CD4+ lymphocytes. The antiviral activity, pharmacokinetics, viral susceptibility, and safety of BMS-488043 were evaluated in an 8-day monotherapy trial. Thirty HIV-1-infected study subjects were randomly assigned to sequential, safety-guided dose panels of 800 and 1,800 mg BMS-488043 or a matched placebo in a 4:1 ratio, and the drug was administered every 12 h with a high-fat meal for 7 days and on the morning of day 8. Dose-related, albeit less-than-dose-proportional, increases in plasma BMS-488043 concentrations were observed. Mean plasma HIV-1 RNA decreases from the baseline for the BMS-488043 800- and 1,800-mg dose groups on day 8 were 0.72 and 0.96 log10 copies/ml, respectively, compared with 0.02 log10 copies/ml for the placebo group. A lower baseline BMS-488043 50% effective concentration (EC50) in the active-treatment groups was predictive of a greater antiviral response. Although absolute drug exposure was not associated with an antiviral response, the trough concentration (Ctrough), adjusted by the baseline EC50 (Ctrough/EC50), was associated with antiviral activity. During dosing, four subjects experienced >10-fold reductions in viral susceptibility to BMS-488043, providing further support of the direct antiviral mechanism of BMS-488043. BMS-488043 was generally safe and well tolerated. These results suggest that further development of this novel class of oral HIV-1 attachment inhibitors is warranted. PMID:21078951

  2. In vivo photoprotective and anti-inflammatory effect of hyperforin is associated with high antioxidant activity in vitro and ex vivo.

    Science.gov (United States)

    Meinke, Martina C; Schanzer, Sabine; Haag, Stefan F; Casetti, Federica; Müller, Marcel L; Wölfle, Ute; Kleemann, Anke; Lademann, Juergen; Schempp, Christoph M

    2012-06-01

    Hyperforin, a major constituent of St. John's Wort (Hypericum perforatum, HP), provides anti-inflammatory, anti-tumor, and anti-bacterial properties. Previous studies have shown anti-oxidative properties of St. John's Wort extracts; however, its free radical scavenging activity in skin cells or skin has not been assessed in detail so far. Therefore, the free radical scavenging activity of hyperforin was tested in the H(2)DCFDA-assay in vitro in HaCaT keratinocytes irradiated with solar simulated radiation. Hyperforin (EC(50) 0.7 μM corresponding to 0.42 μg/ml) was much more effective compared to Trolox (EC(50) 12 μg/ml) and N-acetylcysteine (EC(50) 847 μg/ml) without showing phototoxicity. The radical protection factor of a cream containing 1.5%w/w of a hyperforin-rich HP extract was determined to be 200 × 10(14) radicals/mg, indicating a high radical scavenging activity. The cream was further applied ex vivo on porcine ear skin and significantly reduced radical formation after infrared irradiation. Finally, the UV-protective effect of the HP cream was tested on 20 volunteers in a randomized, double-blind, vehicle-controlled study. HP cream significantly reduced UVB-induced erythema as opposed to the vehicle. Occlusive application of HP cream on non-irradiated test sites did not cause any skin irritation. Taken together, these results demonstrate that hyperforin is a powerful free radical scavenger. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Synthesis, fungicidal activity, and structure-activity relationship of 2-oxo- and 2-hydroxycycloalkylsulfonamides.

    Science.gov (United States)

    Li, Xing-Hai; Wu, De-Cai; Qi, Zhi-Qiu; Li, Xiu-Wei; Gu, Zu-Min; Wei, Song-Hong; Zhang, Yang; Wang, Ying-Zi; Ji, Ming-Shan

    2010-11-10

    To explore new potential fungicides, a series of novel compounds, including 11 2-oxocycloalkylsulfonamide (3) and 21 2-hydroxycycloalkylsulfonamide (4) derivatives, were synthesized and their structures were confirmed by (1)H nuclear magnetic resonance (NMR), infrared (IR), and elemental analysis. The results of the bioassay showed that the compounds 3 and 4 possessed excellent fungicidal activity against Botrytis cinerea Pers. both in vitro and in vivo. The fungicidal activity of the compounds with 7- or 8-membered rings is better than those with 5-, 6-, or 12-membered rings. According to the results of the mycelium growth rate test, the EC50 values of the compounds 3C, 4C, 3D, and 4D were 0.80, 0.85, 1.22, and 1.09 μg/mL, respectively, and similar to or better than commercial fungicide procymidone. The bioassay results of spore germination indicated that most of the compounds exhibited obvious inhibitory effects against B. cinerea and the inhibition rates of 2-oxocycloalkylsulfonamides were higher than 2-hydroxycycloalkylsulfonamides, among them. The EC50 values of compounds 3A, 3B17, 3E, and 4A were 4.21, 4.21 3.24, and 5.29 μg/mL, respectively. Those compounds containing 5- or 6-membered rings showed better activity than those containing 7-, 8-, or 12-membered rings. Furthermore, the results of the pot culture test showed that almost all of the compounds had effective control activity in vivo and 2-hydroxycycloalkylsulfonamides were obviously superior to 2-oxocycloalkylsulfonamides. The compounds 3E, 4C and 4D presented higher control efficacy than procymidone and pyrimethanil against gray mold disease on cucumber plants.

  4. Anti-oxidative and antimicrobial activities of Hieracium pilosella L. extracts

    Directory of Open Access Journals (Sweden)

    LJILJANA P. STANOJEVIC

    2008-05-01

    Full Text Available The anti-oxidative and antimicrobial activities of different extracts from Hieracium pilosella L. (Asteraceae whole plant were investigated. The total dry extracts were determined for all the investigated solvents: methanol, dichloromethane, ethyl acetate and dichloromethane:methanol (9:1. It was found that the highest yield was obtained by extraction with methanol (12.9 g/100 g of dry plant material. Qualitative and quantitative analysis were performed by the HPLC method, using external standards. Chlorogenic acid, apigenin-7-O-glucoside and umbelliferone were detected in the highest quantity in the extracts. The qualitative and quantitative composition of the extracts depends on the solvent used. The 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging effect of the extracts was determined spectrophotometrically. The highest radical scavenging effect was observed in the methanolic extract, both with and without incubation, EC50 = 0.012 and EC50 = 0.015 mg ml-1, respectively. The antimicrobial activities of the extracts towards the bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Salmonella enteritidis and Klebsiella pneumoniae and the fungi (Aspergillus niger and Candida albicans were determined by the disc diffusion method. The minimal inhibitory concentrations were determined for all the investigated extracts against all the mentioned microorganisms.

  5. FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139.

    Science.gov (United States)

    Anas, Andrea Roxanne J; Mori, Akane; Tone, Mineka; Naruse, Chiaki; Nakajima, Anna; Asukabe, Hirohiko; Takaya, Yoshiaki; Imanishi, Susumu Y; Nishizawa, Tomoyasu; Shirai, Makoto; Harada, Ken-Ichi

    2017-08-30

    The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC 50 10.62 µM, which was more efficient than thrombin inhibition of EC 50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF) and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.

  6. Antidiarrheal and antispasmodic activities of Vincetoxicum stocksii are mediated through calcium channel blockade

    Directory of Open Access Journals (Sweden)

    Abdul Jabbar Shah

    2011-03-01

    Full Text Available This study was carried out to explore the mechanism underlying antidiarrheal and antispasmodic activities of Vincetoxicum stocksii. The crude extract of V. stocksii provided 12-24% protection from castor oil-induced diarrhea at the dose of 300-1,000 mg/kg, similar to loperamide. In isolated rabbit jejunum preparations, V. stocksii caused inhibition of the spontaneous and high K+ (80 mM-induced contractions, with respective EC50 values of 2.53 (1.65-3.90 and 0.95 mg/mL (0.63-1.42, similar to that caused by verapamil, suggesting the calcium channel blocking effect. Loperamide caused inhibition of sponta-neous and high K+-induced contraction, with respective EC50 values of 8.59 (6.33-10.11 and 9.12 µM (7.33-12.81. The calcium channel blocking activity was further confirmed when pretreatment of the tissues with V. stocksii (1-3 mg/mL caused a rightward displacement of the Ca++ concentrations response curves, similar to that produced by verapamil; constructed in Ca++ free medium. These data indicate that the crude extract of V. stocksii contains calcium channel blocking constituents that may possibly explain its medicinal use in hyperactive states of gut, such as, diarrhea and spasms.

  7. Research resource: modulators of glucocorticoid receptor activity identified by a new high-throughput screening assay.

    Science.gov (United States)

    Blackford, John A; Brimacombe, Kyle R; Dougherty, Edward J; Pradhan, Madhumita; Shen, Min; Li, Zhuyin; Auld, Douglas S; Chow, Carson C; Austin, Christopher P; Simons, S Stoney

    2014-07-01

    Glucocorticoid steroids affect almost every type of tissue and thus are widely used to treat a variety of human pathological conditions. However, the severity of numerous side effects limits the frequency and duration of glucocorticoid treatments. Of the numerous approaches to control off-target responses to glucocorticoids, small molecules and pharmaceuticals offer several advantages. Here we describe a new, extended high-throughput screen in intact cells to identify small molecule modulators of dexamethasone-induced glucocorticoid receptor (GR) transcriptional activity. The novelty of this assay is that it monitors changes in both GR maximal activity (A(max)) and EC(50) (the position of the dexamethasone dose-response curve). Upon screening 1280 chemicals, 10 with the greatest changes in the absolute value of A(max) or EC(50) were selected for further examination. Qualitatively identical behaviors for 60% to 90% of the chemicals were observed in a completely different system, suggesting that other systems will be similarly affected by these chemicals. Additional analysis of the 10 chemicals in a recently described competition assay determined their kinetically defined mechanism and site of action. Some chemicals had similar mechanisms of action despite divergent effects on the level of the GR-induced product. These combined assays offer a straightforward method of identifying numerous new pharmaceuticals that can alter GR transactivation in ways that could be clinically useful.

  8. Antiviral activity and metal ion-binding properties of some 2-hydroxy-3-methoxyphenyl acylhydrazones.

    Science.gov (United States)

    Carcelli, M; Fisicaro, E; Compari, C; Contardi, L; Rogolino, D; Solinas, C; Stevaert, A; Naesens, L

    2018-02-01

    Here we report on the results obtained from an antiviral screening, including herpes simplex virus, vaccinia virus, vesicular stomatitis virus, Coxsackie B4 virus or respiratory syncytial virus, parainfluenza-3 virus, reovirus-1 and Punta Toro virus, of three 2-hydroxy-3-methoxyphenyl acylhydrazone compounds in three cell lines (i.e. human embryonic lung fibroblast cells, human cervix carcinoma cells, and African Green monkey kidney cells). Interesting antiviral EC 50 values are obtained against herpes simplex virus-1 and vaccinia virus. The biological activity of acylhydrazones is often attributed to their metal coordinating abilities, so potentiometric and microcalorimetric studies are here discussed to unravel the behavior of the three 2-hydroxy-3-methoxyphenyl compounds in solution. It is worth of note that the acylhydrazone with the higher affinity for Cu(II) ions shows the best antiviral activity against herpes simplex and vaccinia virus (EC 50  ~ 1.5 µM, minimal cytotoxic concentration = 60 µM, selectivity index = 40).

  9. Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.

    Science.gov (United States)

    Chen, Yen-Liang; Abdul Ghafar, Nahdiyah; Karuna, Ratna; Fu, Yilong; Lim, Siew Pheng; Schul, Wouter; Gu, Feng; Herve, Maxime; Yokohama, Fumiaki; Wang, Gang; Cerny, Daniela; Fink, Katja; Blasco, Francesca; Shi, Pei-Yong

    2014-02-01

    In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experimental evidence to explain the discrepancy between the in vitro and in vivo results and its implication for drug development. R1479 lost its potency by 125-fold when balapiravir was used to treat primary human peripheral blood mononuclear cells (PBMCs; one of the major cells targeted for viral replication) that were preinfected with dengue virus. The elevated EC(50) was greater than the plasma trough concentration of R1479 observed in dengue patients treated with balapiravir and could possibly explain the efficacy failure. Mechanistically, dengue virus infection triggered PBMCs to generate cytokines, which decreased their efficiency of conversion of R1479 to its triphosphate form (the active antiviral ingredient), resulting in decreased antiviral potency. In contrast to the cytidine-based compound R1479, the potency of an adenosine-based inhibitor of dengue virus (NITD008) was much less affected. Taken together, our results demonstrate that viral infection in patients before treatment could significantly affect the conversion of the prodrug to its active form; such an effect should be calculated when estimating the dose efficacious for humans.

  10. FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139

    Directory of Open Access Journals (Sweden)

    Andrea Roxanne J. Anas

    2017-08-01

    Full Text Available The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 µM, which was more efficient than thrombin inhibition of EC50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.

  11. Ovicidal and larvicidal activity of extracts of Opuntia ficus-indica against gastrointestinal nematodes of naturally infected sheep.

    Science.gov (United States)

    Féboli, Aline; Laurentiz, Antonio C; Soares, Suelen C S; Augusto, Jeferson G; Anjos, Luciano A; Magalhães, Lizandra G; Filardi, Rosemeire S; Laurentiz, Rosangela S

    2016-08-15

    This study describes the in vitro anthelmintic activity of extracts from Opuntia ficus indica against gastrointestinal nematodes of sheep. The anthelmintic activity was evaluated by inhibition of egg hatching, larval development and larval migration assays. The residual aqueous fractions from cladodes and fruits showed higher ovicidal activity with EC50 values of 7.2mg/mL and 1.5mg/mL, respectively. The aqueous, hexane, and ethyl acetate fractions from fruits and the aqueous fraction from cladodes inhibited 100% of larval development at the lowest concentration tested (1.56mg/mL). The crude cladode and fruit ethanolic extracts inhibited larval migration and showed EC50 values of 0.74mg/mL and 0.27mg/mL, respectively. Phytochemical screening detected high concentrations of alkaloids, tannins, flavonoids, and saponins in the fruits and cladodes. The results demonstrated that O. ficus exhibits anthelmintic activity in vitro, suggesting that, beyond its nutritional potential, this plant can also be an ally for parasite control in sheep. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Antiviral activity of the EB peptide against zoonotic poxviruses

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    Altmann Sharon E

    2012-01-01

    Full Text Available Abstract Background The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox. Findings In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice. Conclusions While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.

  13. Cytotoxic and free radical scavenging activities of Zingiberaceous rhizomes

    Directory of Open Access Journals (Sweden)

    Niwat Keawpradub

    2005-07-01

    Full Text Available Methanol extracts, water extracts and volatile oils of the fresh rhizomes of Alpinia galanga, Boesenbergia pandurata, Curcuma longa, Kaempferia galanga and Zingiber officinale have been assessed for free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH radical and cytotoxic activity against MCF7 (breast adenocarcinoma and LS174T (colon adenocarcinoma cell lines. Methanol extract of C. longa exhibited the most pronounced radical scavenging activity with an EC50 value of 9.7 μg/ml, whereas the water extracts and volatile oils showed weak activity. All volatile oils and the methanol extract of C. longa showed strong activity against MCF7 and LS174T with IC50 less than 50 μg/ml. The oils of A. galanga (AGV, B. pandurata (BPV, C. longa (CLV, K. galanga (KGV and Z. officinale (ZOV were analyzed by GC/MS. Trans-3-acetoxy-1,8-cineole, camphor, ar-turmerone, ethyl cinnamate and geranial (E-citral were detected as main compounds in AGV, BPV, CLV, KGV and ZOV, respectively. The novel compound, pcoumaryl- 9-methyl ether, was isolated from methanol extract of A. galanga. ar-Turmerone, curcumin, demethoxycurcumin and bisdemethoxycurcumin were isolated from the methanol extract of C. longa while 6-shogaol, 6-dehydrogingerdione (or 1-dehydrogingerdione and 6-gingerol were isolated from the methanol extract of Z. officinale. Curcumin was the most potent compound for free radical scavenging activity with an EC50 value of 2.0 μg/ml. Demethoxycurcumin was found to be the most active compound against LS174T with an IC50 value of 0.8 μg/ml and 6-shogaol was the most potent compound against MCF7 with an IC50 value of 1.7 μg/ml.

  14. Structure-Antifungal Activity Relationship of Fluorinated Dihydroguaiaretic Acid Derivatives and Preventive Activity against Alternaria alternata Japanese Pear Pathotype.

    Science.gov (United States)

    Nishiwaki, Hisashi; Nakazaki, Shoko; Akiyama, Koichi; Yamauchi, Satoshi

    2017-08-09

    The structure-activity relationship of the antifungal fluorinated dihydroguaiaretic acid derivatives was evaluated. Some of the newly synthesized lignan compounds were found to show higher antifungal activity against phytopathogenic fungi such as Alternaria alternata (Japanese pear and apple pathotypes) and A. citri than the lead compound, 3-fluoro-3'-methoxylignan-4'-ol (3). The broad antifungal spectrum of 3'-hydroxyphenyl derivative 16 was observed, and the 3'-fluoro-4'-hydroxyphenyl derivative 38 was found to show the highest activity against the A. alternata Japanese pear pathotype, with an EC 50 value of 11 μM. The preventive effect of the potent lignan on the infection of A. alternata in the Japanese pear's leaves was also shown.

  15. Reversible anti-settlement activity against Amphibalanus (= Balanus ) amphitrite, Bugula neritina , and Hydroides elegans by a nontoxic pharmaceutical compound, mizolastine

    KAUST Repository

    Zhou, Xiaojian

    2009-11-01

    Mizolastine, an antihistamine pharmaceutical, was found to significantly inhibit larval settlement of the barnacle Amphibalanus (=Balanus) amphitrite, the bryozoan Bugula neritina, and the polychaete Hydroides elegans with EC50 values of 4.2, 11.2, and 4.1 mg ml-1, respectively. No toxicity against the larvae of these three species was observed at the concentration range tested during incubations with mizolastine. To determine whether the anti-settlement activity of mizolastine is reversible, recovery bioassays using these three species were conducted. More than 70% of the larvae that had been exposed for 4 h to mizolastine at concentrations four-fold greater than their respective EC50 values completed normal metamorphosis. The results of the recovery bioassay provide evidence that the antisettlement effect of mizolastine is reversible in addition to being nontoxic. The anti-settlement activities of several intermediates of the synthesis process of mizolastine were also examined. One of the intermediates, 2-chloro-1-(4- fluorobenzyl)-1H-benzo[d]imidazole, inhibited larval settlement and metamorphosis with low toxicity. These results may improve the understanding of the key functional group responsible for the anti-settlement activity of mizolastine. © 2009 Taylor & Francis.

  16. Activated endothelial cells elicit paracrine induction of epithelial chloride secretion. 6-Keto-PGF1alpha is an epithelial secretagogue.

    Science.gov (United States)

    Blume, E D; Taylor, C T; Lennon, P F; Stahl, G L; Colgan, S P

    1998-09-15

    Endothelial cells play a central role in the coordination of the inflammatory response. In mucosal tissue, such as the lung and intestine, endothelia are anatomically positioned in close proximity to epithelia, providing the potential for cell-cell crosstalk. Thus, in this study endothelial-epithelial biochemical crosstalk pathways were studied using a human intestinal crypt cell line (T84) grown in noncontact coculture with human umbilical vein endothelia. Exposure of such cocultures to endothelial-specific agonists (LPS) resulted in activation of epithelial electrogenic Cl- secretion and vectorial fluid transport. Subsequent experiments revealed that in response to diverse stimuli (LPS, IL-1alpha, TNF-alpha, hypoxia), endothelia produce and secrete a small, stable epithelial secretagogue into conditioned media supernatants. Further experiments identified this secretagogue as 6-keto-PGF1alpha, a stable hydrolysis product of prostacyclin (PGI2). Results obtained with synthetic prostanoids indicated that 6-keto-PGF1alpha (EC50 = 80 nM) and PGI2 stable analogues (EC50 = 280 nM) activate the same basolaterally polarized, Ca2+-coupled epithelial receptor. In summary, these findings reveal a previously unappreciated 6-keto-PGF1alpha receptor on intestinal epithelia, the ligation of which results in activation of electrogenic Cl- secretion. In addition, these data reveal a novel action for the prostacyclin hydrolysis product 6-keto-PGF1alpha and provide a potential endothelial- epithelial crosstalk pathway in mucosal tissue.

  17. Quantitative structure-activity relationships of nitroaromatics toxicity to the algae (Scenedesmus obliguus).

    Science.gov (United States)

    Yan, Xiu-Fen; Xiao, He-Ming; Gong, Xue-Dong; Ju, Xue-Hai

    2005-04-01

    The DFT-B3LYP method, with the basis set 6-311G( * *), was employed to calculate the molecular geometries and electronic structures of 25 nitroaromatics. The acute toxicity (-lgEC(50)) of these compounds to the algae (Scenedesmus obliguus) along with hydrophobicity described by logK(OW), and two quantum chemical parameters-energy of the lowest unoccupied molecular orbital, E(LUMO), and the charge of the nitro group, [ForQ(NO2), were used to establish the quantitative structure-activity relationships (QSARs). For 18 mononitro derivatives, the hydrophobicity parameter logK(OW) could interpret the toxic mechanism successfully. Dinitro aromatic compounds were susceptible to be reduced to aniline for their electrophilic nature. Their toxicity was controlled mainly by electronic factors instead of hydrophobicity. The electronic parameters, E(LUMO) and Q(NO2), were used to yield the following model: -lg EC(50) = 3.746 - 25.053 E(LUMO) + 6.481 Q(NO2) (n=22, R=0.926, SE=0.206, F=56.854, Ptoxic values using the above equation are in good agreement with the experimental values.

  18. Antibacterial, Antifungal and antioxidant activities of some medicinal plants.

    Science.gov (United States)

    Wazir, Asma; Mehjabeen, -; Jahan, Noor; Sherwani, Sikander Khan; Ahmad, Mansoor

    2014-11-01

    The purpose of this study was to evaluate the antibacterial, antifungal and antioxidant activities of medicinal plants. The antibacterial activity of methanolic extracts of three medicinal plants (Swertia chirata, Terminalia bellerica and Zanthoxylum armatum) were tested against Gentamicin (standard drug) on eleven gram positive and seventeen gram negative bacteria by agar well method. It was revealed that seven-gram negative and six gram positive bacterial species were inhibited by these plant extracts. Minimum inhibitory concentrations (MIC) of the extracts were determined by broth micro-dilution method. The significant MIC value of Swertia chirata was 20mg/ml against Serratia marcesens, Zanthoxylum armatum was 10 mg/ml against Aeromonas hydrophila and Terminali bellerica was 20mg/ml against Acinetobacter baumanii as well as Serratia marcesens. Antifungal screening was done for methanolic extracts of these plants by agar well method with the 6 saprophytic, 5 dermatophytic and 6 yeasts. In this case Griseofulvin was used as a standard. All saprophytes and dermatophytes were showed resistance by these plants extracts except Microsporum canis, which was inhibited by Z. armatum and S. chirata extracts. The significant MIC value of Zanthoxylum armatum was 10mg/ml against Microsporum canis and Swertia chirata was 10mg/ml against Candida tropicalis. The anti-oxidant study was performed by DPPH free radical scavenging assay using ascorbic acid as a reference standard. Significant antioxidant activities were observed by Swertia chirata and Zanthoxylum armatum at concentration 200μg/ml was 70% DPPH scavenging activity (EC50=937.5μg/ml) while Terminalia bellerica showed 55.6% DPPH scavenging activity (EC50=100μg/ml). This study has shown that these plants could provide potent antibacterial compounds and may possible preventive agents in ROS related ailments.

  19. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Directory of Open Access Journals (Sweden)

    Klingelhoeffer Christoph

    2012-05-01

    Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

  20. Spasmolytic activity of lapachol and its derivatives, α and β-lapachone, on the guinea-pig ileum involves blockade of voltage-gated calcium channels

    Directory of Open Access Journals (Sweden)

    Fabiana A. Cavalcante

    Full Text Available Lapachol, α and β-lapachone are naphthoquinones extracted from species of Tabebuia that have shown antiinflammatory, antibacterial, anticancer and trypanosomicidal properties. The aim of this work was to investigate the spasmolytic effect of these naphthoquinones on the guinea-pig ileum, since other naphthoquinones are known to depress the contractile activity of smooth muscles. Lapachol, α and β-lapachone inhibited the phasic contractions induced by both carbachol (IC50 = 1.5 ± 0.2 x 10-4; 7.3 ± 0.9 x 10-5 and 3.2 ± 0.5 x 10-5 M, respectively and histamine (IC50 = 3.6± 0.5; 3.6 ± 0.7 and 3.3 ± 0.6 x 10-5 M, respectively. These compounds also relaxed the ileum pre-contracted with KCl (EC50 = 1.2 ± 0.4; 4.3 ± 0.8 and 2.7 ± 0.2 x 10-5 M, respectively; carbachol (EC50 = 2.6 ± 0.7; 3.5 ± 0.5 and 2.2 ± 0.7 x 10-5 M, respectively or histamine (EC50 = 3.0 ± 0.8; 1.1 ± 0.3 and 3.3 ± 0.6 x 10-5 M, respectively in a concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-gated calcium channels (Ca v. β-lapachone antagonized (pD'2 = 5.73 ± 0.12; slope = 1.51 ± 0.05 CaCl2-induced contractions in depolarizing medium nominally without Ca2+. The finding that β-lapachone inhibited the tonic contractions induced by S-(--Bay K8644 (EC50 = 1.4 ± 0.1 x 10-5 M is suggestive that the L-type CaV is involved. In conclusion, lapachol, α and β-lapachone showed non-selective spasmolytic activity in guinea-pig ileum, and β-lapachone exerts this effect by to blockade of L-type CaV channels.

  1. Efavirenz Mannich bases: synthesis, anti-HIV and antitubercular activities.

    Science.gov (United States)

    Sriram, Dharmarajan; Banerjee, Debjani; Yogeeswari, Perumal

    2009-02-01

    A series of efavirenz Mannich bases has been synthesized by reacting efavirenz, formaldehyde, and various aryl substituted piperazines using microwave irradiation (yield 35-88%). The synthesized compounds were evaluated for in-vitro anti-HIV and antimycobacterial activities. The in-vitro antiretroviral activities indicated that compound 7-(4-((6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2-oxo-2H-benzo[d] [1,3]oxazin-1 (4H)-yl)methyl)-3-methylpiperazin-l -yl)-1-cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid (4i) was equipotent to efavirenz with EC(50) of 2.4 nM. Compound 4i also inhibited M. tuberculosis with minimum inhibitory concentration of 0.2 microg/mL.

  2. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction

    Science.gov (United States)

    Namkung, Wan; Yao, Zhen; Finkbeiner, Walter E.; Verkman, A. S.

    2011-01-01

    TMEM16A (ANO1) is a calcium-activated chloride channel (CaCC) expressed in secretory epithelia, smooth muscle, and other tissues. Cell-based functional screening of ∼110,000 compounds revealed compounds that activated TMEM16A CaCC conductance without increasing cytoplasmic Ca2+. By patch-clamp, N-aroylaminothiazole “activators” (Eact) strongly increased Cl− current at 0 Ca2+, whereas tetrazolylbenzamide “potentiators” (Fact) were not active at 0 Ca2+ but reduced the EC50 for Ca2+-dependent TMEM16A activation. Of 682 analogs tested, the most potent activator (Eact) and potentiator (Fact) produced large and more sustained CaCC Cl− currents than general agonists of Ca2+ signaling, with EC50 3–6 μM and Cl− conductance comparable to that induced transiently by Ca2+-elevating purinergic agonists. Analogs of activators were identified that fully inhibited TMEM16A Cl− conductance, providing further evidence for direct TMEM16A binding. The TMEM16A activators increased CaCC conductance in human salivary and airway submucosal gland epithelial cells, and IL-4 treated bronchial cells, and stimulated submucosal gland secretion in human bronchi and smooth muscle contraction in mouse intestine. Small-molecule, TMEM16A-targeted activators may be useful for drug therapy of cystic fibrosis, dry mouth, and gastrointestinal hypomotility disorders, and for pharmacological dissection of TMEM16A function.—Namkung, W., Yao, Z., Finkbeiner, W. E., Verkman, A. S. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. PMID:21836025

  3. An atypical residue in the pore of Varroa destructor GABA-activated RDL receptors affects picrotoxin block and thymol modulation.

    Science.gov (United States)

    Price, Kerry L; Lummis, Sarah C R

    2014-12-01

    GABA-activated RDL receptors are the insect equivalent of mammalian GABAA receptors, and play a vital role in neurotransmission and insecticide action. Here we clone the pore lining M2 region of the Varroa mite RDL receptor and show that it has 4 atypical residues when compared to M2 regions of most other insects, including bees, which are the major host of Varroa mites. We create mutant Drosophila RDL receptors containing these substitutions and characterise their effects on function. Using two electrode voltage clamp electrophysiology we show that one substitution (T6'M) ablates picrotoxin inhibition and increases the potency of GABA. This mutation also alters the effect of thymol, which enhances both insect and mammalian GABA responses, and is widely used as a miticide. Thymol decreases the GABA EC50 of WT receptors, enhancing responses, but in T6'M-containing receptors it is inhibitory. The other 3 atypical residues have no major effects on either the GABA EC50, the picrotoxin potency or the effect of thymol. In conclusion we show that the RDL 6' residue is important for channel block, activation and modulation, and understanding its function also has the potential to prove useful in the design of Varroa-specific insecticidal agents. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Composition, antioxidant and antimicrobial activity of the essential oils of a full grown tree of Pinus cembra L. from the Calimani mountains (Romania

    Directory of Open Access Journals (Sweden)

    Apetrei Lungu Cristina

    2013-01-01

    Full Text Available This study was carried out to investigate the chemical composition, the antioxidant and antimicrobial effects of the essential oils of Pinus cembra L. needles and twigs. The chemical composition was analyzed using both GC and GC-MS techniques. α-Pinene (69.14% was the major constituent of the needle essential oil while the twig essential oil was characterized by a high content of limonene+ β-phellandrene (40.97% and α-pinene (24.94%. The needle and twig essential oils showed weak DPPH radical scavenging effects (EC50=19.93±0.75 and EC50=18.66±0.70 mg ml-1, respectively. In antimicrobial assays, both essential oils showed high activity against Sarcina lutea and Staphylococcus aureus and no activity against Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The needle and twig essential oils had similar antimicrobial effects against Sarcina lutea with MIC and MBC values of 0.12 and 0.24 mg ml-1, respectively. The twig essential oil (MIC=1.95 mg ml-1, MBC=3.9 mg ml-1 was more active against Staphylococcus aureus than the needle essential oil (MIC=3.9 mg ml-1, MBC=15.62 mg ml-1 and also exhibited a moderate activity against Candida albicans (MIC=7.81 mg ml-1, MFC=15.62 mg ml-1.

  5. Anti-inflammatory and angiogenic activity of polysaccharide extract obtained from Tibetan kefir.

    Science.gov (United States)

    Prado, Maria Rosa Machado; Boller, Christian; Zibetti, Rosiane Guetter Mello; de Souza, Daiany; Pedroso, Luciana Lopes; Soccol, Carlos Ricardo

    2016-11-01

    The search for new bioactive molecules is a driving force for research pharmaceutical industries, especially those molecules obtained from fermentation. The molecules possessing angiogenic and anti-inflammatory attributes have attracted attention and are the focus of this study. Angiogenic activity from kefir polysaccharide extract, via chorioallantoic membrane assay, exhibited a pro-angiogenic effect compared with vascular endothelial factor (pro-angiogenic) and hydrocortisone (anti-angiogenic) activity as standards with an EC50 of 192ng/mL. In terms of anti-inflammatory activity determined via hyaluronidase enzyme assay, kefir polysaccharide extract inhibited the enzyme with a minimal activity of 2.08mg/mL and a maximum activity of 2.57mg/mL. For pharmaceutical purposes, kefir polysaccharide extract is considered to be safe because it does not inhibit VERO cells in cytotoxicity assays. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Polyyne hybrid compounds from Notopterygium incisum with peroxisome proliferator-activated receptor gamma agonistic effects.

    Science.gov (United States)

    Liu, Xin; Kunert, Olaf; Blunder, Martina; Fakhrudin, Nanang; Noha, Stefan M; Malainer, Clemens; Schinkovitz, Andreas; Heiss, Elke H; Atanasov, Atanas G; Kollroser, Manfred; Schuster, Daniela; Dirsch, Verena M; Bauer, Rudolf

    2014-11-26

    In the search for peroxisome proliferator-activated receptor gamma (PPARγ) active constituents from the roots and rhizomes of Notopterygium incisum, 11 new polyacetylene derivatives (1-11) were isolated. Their structures were elucidated by NMR and HRESIMS as new polyyne hybrid molecules of falcarindiol with sesquiterpenoid or phenylpropanoid moieties, named notoethers A-H (1-8) and notoincisols A-C (9-11), respectively. Notoincisol B (10) and notoincisol C (11) represent two new carbon skeletons. When tested for PPARγ activation in a luciferase reporter assay with HEK-293 cells, notoethers A-C (1-3), notoincisol A (9), and notoincisol B (10) showed promising agonistic activity (EC50 values of 1.7 to 2.3 μM). In addition, notoincisol A (9) exhibited inhibitory activity on NO production of stimulated RAW 264.7 macrophages.

  7. Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352

    DEFF Research Database (Denmark)

    Dupuis, Delphine S; Schrøder, Rikke L; Jespersen, Thomas

    2002-01-01

    The novel anti-ischemic compound, BMS-204352 ((3S)-(+)-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one)), strongly activates the voltage-gated K+ channel KCNQ5 in a concentration-dependent manner with an EC50 of 2.4 microM. At 10 microM, BMS-204352 increased......, BMS-204352 (10 microM) did not significantly shift the KCNQ5 activation curves (threshold and potential for half-activation, V1/2), as observed for the other KCNQ channels. In the presence of BMS-204352, the activation and deactivation kinetics of the KCNQ5 currents were slowed as the slow activation...

  8. Anti-UV/HIV activity of Kampo medicines and constituent plant extracts.

    Science.gov (United States)

    Kato, Takao; Horie, Norio; Matsuta, Tomohiko; Naoki, Umemura; Shimoyama, Tetsuo; Kaneko, Tadayoshi; Kanamoto, Taisei; Terakubo, Shigemi; Nakashima, Hideki; Kusama, Kaoru; Sakagami, Hiroshi

    2012-01-01

    In order to search for new biological activities of Kampo medicines and their constituent plant extracts, we investigated whether they protect the cells from the cytotoxicity induced by UV irradiation and human immunodeficiency virus (HIV) infection. Anti-UV/HIV activity (SI value) was evaluated as the ratio of the CC(50) (concentration that reduced the viable cell number by 50%) to the EC(50) (the concentration that increased the viability of UV-irradiated or HIV-infected cells to 50%): SI=CC(50)/EC(50). The content of glycyrrhizin in each sample was determined by high performance liquid chromatography (HPLC). Caspase-3/-7 activity was assayed by cleavage of poly ADP ribose polymerase using western blot analysis. Among 25 plant extracts, Gardenia fruit had the highest anti-UV activity (SI≥8.0), followed by Glycyrrhiza (SI=4.3), Coptis rhizoma (SI=1.5), Cimicifuga rhizoma (SI>1.4), Saposhnikovia root (SI>1.3) and Japanese Gentian (SI>1.1). Among ten Kampo medicines, Unseiin and Hangesyashinto (SI>4.9) had the highest anti-UV activity, followed by Shosaikoto (SI>4.3), Saireito (SI>3.4), Rikkosan (SI>1.2) and Kikyoto (SI=1.1). Glycyrrhiza inhibited UV-induced caspase-3/-7 activation. Only Polyporus sclerotium (SI>4.4), Gardenia fruit (SI>2.7), Atractylodes lancea rhizoma (SI>1.9), Cnidium rhizoma (SI>1.5) and Japanese Angelica root (SI>1.1) exhibited some anti-HIV activity. There was no apparent correlation of their anti-UV/HIV activity and content of glycyrrhizin, a major component of Glycyrrhiza, which exhibited much higher anti-UV activity (SI=20.6) and some anti-HIV activity (SI>2.0). The present study suggests the involvement of substances other than glycyrrhizin in the anti-UV/HIV activity of Kampo medicines and their constituent plant extracts.

  9. Quantitative structure–activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes)

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Hongkang [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Morandi, Garrett D. [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Brown, R. Stephen [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Snieckus, Victor; Rantanen, Toni [Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Jørgensen, Kåre B. [Department of Mathematics and Natural Sciences, University of Stavanger, 4036 Stavanger (Norway); Hodson, Peter V., E-mail: peter.hodson@queensu.ca [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada)

    2015-02-15

    Highlights: • Medaka embryos were exposed to alkyl chrysenes and benzo[a]anthracenes (BAA). • Concentrations were kept constant by partition controlled delivery. • Chrysene was not toxic within solubility limits, in contrast to BAA. • Alkylation increased the toxicity of chrysene and BAA. • Toxicity was related to hydrophobicity and to specific modes of action. - Abstract: Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and log K{sub ow} values provided a rough estimation of structure–activity relationships for alkyl-PAHs, but K{sub ow} alone did not provide

  10. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Science.gov (United States)

    2012-01-01

    Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L). Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide

  11. Carnosic acid and carnosol, phenolic diterpene compounds of the labiate herbs rosemary and sage, are activators of the human peroxisome proliferator-activated receptor gamma.

    Science.gov (United States)

    Rau, Oliver; Wurglics, Mario; Paulke, Alexander; Zitzkowski, Jessica; Meindl, Nadine; Bock, Andreas; Dingermann, Theodor; Abdel-Tawab, Mona; Schubert-Zsilavecz, Manfred

    2006-08-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand activated transcription factor, belonging to the metazoan family of nuclear hormone receptors. Activation of PPARgamma increases the transcription of enzymes involved in primary metabolism, leading to lower blood levels of fatty acids and glucose. Hence, PPARgamma represents the major target for the glitazone type of drugs currently being used clinically for the treatment of type 2 diabetes. Furthermore, activators of PPARgamma show beneficial anti-inflammatory and anti-tumour effects. Utilizing a fusion receptor of the yeast Gal4-DNA binding domain joined to the hinge region and ligand binding domain of the human PPARgamma in combination with a Gal4-driven luciferase reporter gene, cotransfected into Cos7 cells, we tested sage and rosemary extracts prepared with 80 % aqueous ethanol for possible PPARgamma activation. This revealed that both extracts are capable of selectively activating Gal4-PPARgamma fusion receptor, in a concentration-dependent manner, with EC (50) values of 22.8 +/- 8.4 mg/L and 33.7 +/- 7.3 mg/L for rosemary and sage, respectively. Subsequent analysis of the characteristic constituents revealed the phenolic diterpene compounds carnosol, present in both herbs, and carnosic acid to be active principles of these extracts, showing EC (50) values of 41.2 +/- 5.9 microM and 19.6 +/- 2.0 microM, respectively. Thus it can be concluded that the glucose lowering effect reported recently for rosemary may be attributed to PPARgamma activation. Moreover, our observations may also explain the anti-inflammatory and antiproliferative effects of both compounds published previously.

  12. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

    Science.gov (United States)

    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  13. Chemistry and Antiviral Activity of Arrabidaea pulchra (Bignoniaceae

    Directory of Open Access Journals (Sweden)

    José D. Souza Filho

    2013-08-01

    Full Text Available The aim of the present work was to carry out a bioguided isolation of antiviral chemical constituents from an ethanol extract of leaves from Arrabidaea pulchra (Cham. Sandwith (EEAPL that had shown in vitro activity in a previous screening using DNA and RNA viruses. The activity of EEPAL was evaluated against the DNA viruses Human herpesvirus 1 (HSV-1 and Vaccinia virus Western Reserve (VACV-WR as well as against the RNA viruses Murine encephalomyocarditis virus (EMCV, and Dengue virus 2 (DENV-2 by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT colorimetric assay. Cytotoxicity was determined in LLCMK2 and Vero cells and the Selectivity Indexes (SI were calculated. The most potent effect was observed against DENV-2 (EC50 46.8 ± 1.6 µg mL−1; SI 2.7. For HSV-1 and VACV-WR EC50 values > 200 µg mL−1 were determined, while no inhibition of the cytopathic effect was observed with EMCV. Bioguided fractionation of EEAPL by partition between immiscible solvents followed by chromatography over a Sephadex LH20 column afforded two arylpropanoid glycosides, verbascoside (AP 1 and caffeoylcalleryanin (AP 2, along with a terpenoid, ursolic acid (AP 3. AP 1 and AP 3 exhibited similar anti-DENV-2 profiles, with SI values of 3.8 and 3.1, respectively, while AP 2 was the most effective anti-DENV-2 constituent, with a SI of 20.0. Our results show that A. pulchra leaves ethanol extract (EEAPL affords compounds with antiviral activity, mainly against DENV-2.

  14. Phytochemical Contents and Antioxidant and Antiproliferative Activities of Selected Black and White Sesame Seeds

    Science.gov (United States)

    Abbasi, Arshad Mehmood; Zheng, Bisheng

    2016-01-01

    Sesame (Sesamum indicum L.) seeds are popular nutritional food but with limited knowledge about their antioxidant and antiproliferative activities of various varieties. Phytochemical profiles and antioxidant and antiproliferative activities of six varieties of sesame (Sesamum indicum L.) seeds were studied. Fenheizhi3 (black) cultivar exhibited the maximum contents of total phenolics and lignans and values of total oxygen radical absorbance capacity (ORAC) and antiproliferative activity (EC50) against HepG2 cells. Bound ORAC values showed strong associations with bound phenolics contents (r = 0.976, p 0.8, p < 0.05). Interestingly, nonlignan components in bound phenolics contributed to the antioxidant and antiproliferative activities. This study suggested that Fenheizhi3 variety is superior to the other five varieties as antioxidant supplements. PMID:27597975

  15. Diketopiperazines and 2H-pyran-2-ones with antioxidant activity from the rice fermented with Aspergillus luchuensis.

    Science.gov (United States)

    Sun, Shanshan; Ma, Ke; Tao, Qiaoqiao; Han, Junjie; Bao, Li; Liu, Li; Liu, Hongwei

    2018-03-01

    Aspergillus luchuensis is widely used as a starter of saccharification in the koji industry, but no secondary metabolites have been reported from this fungus. Herein, we report the isolation and identification of four new diketopiperazine derivatives (1-4), one new methyl 4-(3-acetyl-2, 6-dihydroxyphenyl)-2-methoxybutanoate (5), and six known compounds (6-11) from the rice koji of A. luchuensis. The structures of 1-5 were determined by extensive spectral analysis including 1D and 2D NMR, HRESIMS, and CD, and ECD calculation. In antioxidant assays, compound 10 displayed moderate DPPH scavenging activity with an EC 50 value of 60.8μM; compounds 1-4, 10 and 11 showed reducing ability with EC 50 values ranging from 8.73 to 176.39μM. Compounds 1-11 showed no cytotoxicity against cell lines A549, K562, ASPC, and H460 at 200μM. Our current reports support the safety of A. luchuensis in food chemistry and confirm this fungus to be a new source of natural antioxidants. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. An in vitro larval migration assay for assessing anthelmintic activity of different drug classes against Ascaris suum.

    Science.gov (United States)

    Zhao, Jianguo; Williams, Andrew R; Hansen, Tina Vicky Alstrup; Thamsborg, Stig M; Cai, Jianping; Song, Shuaibao; Chen, Gang; Kang, Ming; Zhang, Zhuangzhi; Liu, Qun; Han, Qian

    2017-04-30

    In vitro methods have been developed for the detection of anthelmintic resistance in a range of nematode species. However, the life cycle of Ascaris suum renders the commonly used egg hatch assay and larval development assay unusable. In this study we developed a combined multi-well culture and agar gel larval migration assay to test the effect of benzimidazole and tetrahydropyrimidin/imidazothiazole anthelmintics against nine isolates of A. suum collected from locations in China and Denmark. Drugs tested were thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel. The percentages of larvae that migrated to the surface of each treated and control well were used to calculate the drug concentration which inhibits 50% of the larvae migration (EC 50 ). The values of EC 50 of thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel against A. suum isolates ranged 74-150, 4.9-13.9, 2.3-4.3, 358-1150 and 1100-4000nM, respectively. This combined multi-well culture and agar gel larval migration assay was a sensitive bioassay for anthelmintic activity and could serve as an in vitro method to detect for lowered drug efficacy against A. suum or possibly to screen for anthelmintic drug candidates. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Handwashing, sanitation and family planning practices are the strongest underlying determinants of child stunting in rural indigenous communities of Jharkhand and Odisha, Eastern India: a cross-sectional study.

    Science.gov (United States)

    Saxton, Jennifer; Rath, Shibanand; Nair, Nirmala; Gope, Rajkumar; Mahapatra, Rajendra; Tripathy, Prasanta; Prost, Audrey

    2016-10-01

    The World Health Organisation has called for global action to reduce child stunting by 40% by 2025. One third of the world's stunted children live in India, and children belonging to rural indigenous communities are the worst affected. We sought to identify the strongest determinants of stunting among indigenous children in rural Jharkhand and Odisha, India, to highlight key areas for intervention. We analysed data from 1227 children aged 6-23.99 months and their mothers, collected in 2010 from 18 clusters of villages with a high proportion of people from indigenous groups in three districts. We measured height and weight of mothers and children, and captured data on various basic, underlying and immediate determinants of undernutrition. We used Generalised Estimating Equations to identify individual determinants associated with children's height-for-age z-score (HAZ; p family planning, reducing diarrhoeal infections, improving handwashing practices, increasing access to income and strengthening health and sanitation infrastructure. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

  18. Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.

    Science.gov (United States)

    Alam, Zohaib; Al-Mahdi, Zainab; Zhu, Yali; McKee, Zachary; Parris, Deborah S; Parikh, Hardik I; Kellogg, Glen E; Kuchta, Alison; McVoy, Michael A

    2015-02-01

    Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238-265μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3μM, significantly below its 50% cytotoxic concentration of 216μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study.

    Science.gov (United States)

    Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

    2017-01-01

    The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC 50 ) of ACh in the presence of atropine (10 -6 M; P pheniramine maleate (10 -6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC 50 of histamine alone. From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.

  20. Synthesis and antiviral activity of cyclopropyl-spirocarbocyclic adenosine, (4R,5S,6R,7R)-4-(6-amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro[2.4]heptane-5,6-diol against hepatitis C virus.

    Science.gov (United States)

    Gadthula, Srinivas; Rawal, Ravindra K; Sharon, Ashoke; Wu, Dong; Korba, Brent; Chu, Chung K

    2011-07-01

    An efficient method was developed for the synthesis of 6-exocyclic methylene carbocyclic intermediate 4. The Simmons-Smith cyclopropanation protocol was applied on the 6-exocyclic methylene of intermediate 4 and demonstrated its utility for the synthesis of novel class of a spiro-carbocyclic nucleoside analog 8. The titled compound 8 demonstrated a significant antiviral activity against HCV with EC(50) values of 0.273 and 0.368 μM in genotypes 1A and 1B, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Aalkjær, Christian; Nilsson, Holger

    2004-01-01

    M) in the pipette solution. The current was found to be a calcium-activated chloride current with an absolute requirement for cyclic GMP (EC50 6.4 microM). The current could be activated by the constitutively active subunit of PKG. Current activation was blocked by the protein kinase G antagonist Rp-8-Br......We have previously demonstrated the presence of a cyclic GMP (cGMP)-dependent calcium-activated inward current in vascular smooth-muscle cells, and suggested this to be of importance in synchronizing smooth-muscle contraction. Here we demonstrate the characteristics of this current. Using...... conventional patch-clamp technique, whole-cell currents were evoked in freshly isolated smooth-muscle cells from rat mesenteric resistance arteries by elevation of intracellular calcium with either 10 mM caffeine, 1 microM BAY K8644, 0.4 microM ionomycin, or by high calcium concentration (900 n...

  2. Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action

    Science.gov (United States)

    Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

    2018-03-01

    Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC50 and EC50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature.

  3. Design, Synthesis, and Structure-Activity Relationship of New Pyrimidinamine Derivatives Containing an Aryloxy Pyridine Moiety.

    Science.gov (United States)

    Guan, Aiying; Liu, Changling; Chen, Wei; Yang, Fan; Xie, Yong; Zhang, Jinbo; Li, Zhinian; Wang, Mingan

    2017-02-15

    The pyrimidinamine diflumetorim is an ideal template for the discovery of agrochemical lead compounds due to its unique mode of action, novel chemical structure, and lack of reported resistance. To develop a new pyrimidinamine fungicide effective against cucumber downy mildew (CDM), a series of new pyrimidinamine derivatives containing an aryloxy pyridine moiety were designed and synthesized by employing the recently reported intermediate derivatization method (IDM). The structures of all compounds were identified by 1 H NMR, elemental analyses, HRMS, and X-ray diffraction. Bioassays demonstrated that some of the title compounds exhibited excellent fungicidal activities against CDM. Compound 9 gave the best activity (EC 50 = 0.19 mg/L), which is significantly better than the commercial fungicides diflumetorim, flumorph, and cyazofamid. The relationship between structure and fungicidal activity of the synthesized pyrimidinamines was explored. The study showed that compound 9 is a promising fungicide candidate for further development.

  4. Synthesis and fungicidal activity of tryptophan analogues - the unexpected calycanthaceous alkaloid derivatives.

    Science.gov (United States)

    Zheng, Shaojun; Gu, Yongdong; Li, Longbo; Zhu, Rui; Cai, Xingwei; Bai, Hongjin; Zhang, Jiwen

    2017-05-01

    A series of 21 N-protected tryptophan derivatives were synthesised from tryptophan in good yields. Their structures were characterised by IR, 1 H NMR, 13 C NMR, DEPT (90° and 135°) and MS analysis. The synthesised compounds were evaluated against a wide variety of plant pathogen fungi. Compounds a19 and a21 displayed activity against Fusarium oxysporum (F. oxysporum), and compound a21 showed high activity against F. oxysporum and Eggplant Verticillium, with EC 50 values of 58.27 and 77.39 μg mL -1 , respectively. Considering that the bioassay of the title compounds was evaluated, effects of the chain alkyl substituents may contribute to the significant variations in fungicidal potency. Their structure-antifungal activity relationships were also discussed. These results will pave the way for further design, structural modification and development of calycanthaceous alkaloids as antimicrobial agents.

  5. Synthesis of PPAR-γ Activators Inspired by the Marine Natural Product, Paecilocin A

    Directory of Open Access Journals (Sweden)

    Bin Xiao

    2014-02-01

    Full Text Available A series of N-substituted phthalimide derivatives were synthesized based on a pharmacophore study of paecilocin A (a natural PPAR-γ agonist and synthetic leads. The introduction of hydrophilic and hydrophobic groups to the phthalimide skeleton yielded compounds 3–14. Compound 7 showed significant PPAR-γ activation in a luciferase assay using rat liver Ac2F cells. Docking simulations showed that a free hydroxyl group on the phthalimide head and a suitable hydrophilic tail, including a phenyl linker, were beneficial for PPAR-γ activation. Compound 7 and rosiglitazone concentration-dependently activated PPAR-γ with EC50 values of 0.67 μM and 0.028 μM, respectively. These phthalimide derivatives could be further investigated as a new class of PPAR-γ ligands.

  6. N-(4-((E)-3-arylacryloyl)phenyl)acetamide derivatives and their antileishmanial activity

    International Nuclear Information System (INIS)

    Pacheco, Dency J.; Trilleras, Jorge; Prent, Luis; Coaves, Tobinson; Quiroga, Jairo; Gutierrez, Jennifer; Delgado, Gabriela; Marin, Juan C.

    2013-01-01

    The antileishmanial activity of a series of enonic derivatives (chalcones) synthesized via Claisen-Schmidt condensation reactions assisted by ultrasonic radiation was characterized by analyzing their cytotoxicity against Leishmania (Viannia) panamensis promastigotes, a species responsible for over 90% of Leishmania cases in Colombia. Two compounds were active against Leishmania with selectivity indexes of LC 50 EC 50 -1 (lethal concentration 50 and effective concentration 50) higher than 27 and 3, respectively. These results suggest that a substitution on one of the two chalcone rings (aromatic ring A) with oxygen is convenient. Compound 3g should be further investigated for its antileishmanial activity, especially for being easy to obtain in high yields, making it possible to produce drugs for the treatment of cutaneous leishmaniasis. (author)

  7. Activity and Safety of Synthetic Lectins Based on Benzoboroxole-Functionalized Polymers for Inhibition of HIV Entry

    Science.gov (United States)

    Mahalingam, Alamelu; Geonnotti, Anthony R.; Balzarini, Jan; Kiser, Patrick F.

    2011-01-01

    Lectins derived from plant and microbial sources constitute a vital class of entry inhibitors that target the oligomannose residues on the HIV envelope gp120. Despite their potency and specificity, success of lectin-based entry inhibitors may be impeded by issues in regards to economical production, formulation and potential mitogenicity. Therefore, there exists a gap in the HIV therapeutics pipeline that underscores the need for mass producible, synthetic, broad-spectrum, and biocomptabile inhibitors of HIV entry. Here, we present the development of a polymeric synthetic lectin, based on benzoboroxole (BzB), which exhibits weak affinity (~25 M−1) for non-reducing sugars, similar to those found on the HIV envelope. High molecular weight BzB-functionalized polymers demonstrated antiviral activity that increased with an increase in ligand density and molecular weight of the polymer construct; revealing that polyvalency improves activity. Polymers showed significant increase in activity from 25 to 75 mol% BzB functionalization with EC50 of 15 μM and 15 nM, respectively. A further increase in mole functionalization to 90% resulted in an increase of the EC50 (59 ± 5 nM), likely due to the elongated rigid structure of the polymer chain compelled by electrostatic repulsion between the boronic acid groups. An increase in molecular weight of the polymer at 50 mol% BzB functionalization showed a gradual but significant increase in antiviral activity, with the highest activity seen with the 382 kDa polymer (EC50 of 1.1 ± 0.5 nM in CEM cells and 11 ± 3 nM in TZM-bl cells). Supplementing the polymer backbone with 10 mol% sulfonic acid not only increased the aqueous solubility of the polymers by at least 50-fold, but also demonstrated a synergistic increase in anti-HIV activity (4.0 ± 1.5 nM in TZM-bl cells), possibly due to electrostatic interactions between the negatively charged polymer backbone and the positively charged V3-loop in the gp120. The benzoboroxole

  8. Prostate volume is strongest predictor of cancer diagnosis at transrectal ultrasound-guided prostate biopsy with prostate-specific antigen values between 2.0 and 9.0 ng/mL.

    Science.gov (United States)

    Al-Azab, Rami; Toi, Ants; Lockwood, Gina; Kulkarni, Girish S; Fleshner, Neil

    2007-01-01

    Data have suggested benign prostatic hyperplasia, and not cancer, as the major reason for elevated prostate-specific antigen (PSA) values between 2.0 and 9.0 ng/mL. If this hypothesis were correct, within these ranges, a smaller prostate volume would be a stronger predictor of cancer than the PSA level itself (the relative contribution from cancer is greater in smaller glands). We examined our institutional data set of transrectal ultrasound-guided procedures from 2000 to 2003. We studied patients who presented for their first prostate biopsy with a PSA level of 2.0 to 9.0 ng/mL. The indications for biopsy were elevated age-specific PSA level or abnormal digital rectal examination findings. Other covariates included patient age, abnormal transrectal ultrasound findings, transrectal ultrasound volume, and biopsy sampling scheme. Univariate analyses were used to assess the association between each variable and cancer diagnosis. Multivariate logistic regression modeling was then used to determine the adjusted risk factors for cancer at biopsy. On univariate analyses, all measured covariates were predictive of cancer. On multivariate modeling, the significant risk factors (in order of strength) for positive biopsy findings were smaller prostate volume (odds ratio [OR] 0.26, P <0.001), increasing age (OR 1.72, P <0.001), increasing PSA (OR 1.64, P <0.001), and the presence of hypoechoic lesions (OR 2.42, P <0.001). When the PSA level is in the 2.0 to 9.0 ng/mL range, a smaller prostate volume is the strongest predictor of cancer detection. These data support previous studies suggesting the amount of benign prostatic hyperplasia, and not cancer, as the major factor responsible for elevated PSA.

  9. Antiradical and Cytotoxic Activities of Varying Polarity Extracts of the Aerial Part of Euphorbia hirta L.

    Directory of Open Access Journals (Sweden)

    Shanmugapriya Perumal

    2013-01-01

    Full Text Available Euphorbia hirta is a well-known ethnomedicinal plant with diverse biological activities. The aim of the present study is to investigate the antiradical activities of various solvent extracts of the aerial part of E. hirta as well as to determine the possible cytotoxicity of these extracts. The aerial part of E. hirta was extracted with different solvent systems in order to increase polarity. The solvents used were hexane, dichloromethane (DCM, ethyl acetate (EA, ethanol (EtOH, and methanol (MeOH. The contents of total phenols and total flavonoids were analyzed by UV spectrophotometry, whereas the potential free radical-scavenging activities of the extracts were evaluated using the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH, the β-carotene-linoleic acid bleaching system, and reducing power. The EtOH extract exhibited the highest total phenolic content (237.9±2.26 mg GAE/g, and DCM extract scored the highest total flavonoid content (121±0.15 mg CE/g. The MeOH extract showed a potent free radical-scavenging activity as evidenced by low EC50 at 42.81 µg/mL. Interestingly, the EtOH extract demonstrated the highest reducing power activity with EC50 value of 6.18 µg/mL. In β-carotene-linoleic acid assay, oxidation of linoleic acid was effectively inhibited by DCM extract with 96.15±0.78%. All the extracts showed no cytotoxic activity against Vero cells.

  10. Enhanced adenylate cyclase activity of turkey erythrocytes following treatment with beta-adrenergic receptor antagonists.

    Science.gov (United States)

    Peters, J R; Nambi, P; Sibley, D R; Lefkowitz, R J

    1984-12-15

    The turkey erythrocyte contains a beta 1-adrenergic receptor-linked adenylate cyclase system. We have examined the effects of pretreatment with receptor antagonists on adenylate cyclase activity and the individual components in the pathway of enzyme activation in this system. Isoproterenol-stimulated adenylate cyclase activity is increased by 30% (P less than 0.01) over control in membranes derived from cells preincubated with the antagonist propranolol. The effect is stereospecific and dose-related with a EC50 of 100 nM for the (-) isomer. The time course of effect is rapid being complete by 90 min. Non-receptor mediated stimulation of adenylate cyclase activity by manganese ion, forskolin and NaF is similarly enhanced following propranolol pretreatment. Sensitization of adenylate cyclase activity also occurs following pretreatment with a number of antagonists but is not seen after preincubation with pindolol or practolol. Quantitation of beta-adrenergic receptor (R) density using [125I]cyanopindolol indicates no difference between membranes derived from control and antagonist pretreated cells. Coupling of R with the guanine nucleotide regulatory protein (N) as assessed by high affinity agonist binding is unchanged following pretreatment. The efficacy of 5'-guanylylimidodiphosphate Gpp(NH)p in producing a shift of agonist binding curves associated with destabilization of high affinity H-R-N complexes, is also the same (EC50 = 0.2 microM) in membranes from control and antagonist treated cells. The isoproterenol stimulated rate of release of [3H]GDP from membranes preloaded with [3H]GTP as an index of formation of an active form of the N protein is similarly unaffected by antagonist preincubation. We conclude that the mechanism of the observed sensitization of turkey erythrocyte adenylate cyclase by beta-adrenergic antagonists is receptor mediated and likely involves facilitation of N interaction with the catalytic subunit of the enzyme.

  11. Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic activity, via a pathway involving NMU1 receptor activation

    Science.gov (United States)

    Dass, N B; Bassil, A K; North-Laidler, V J; Morrow, R; Aziz, E; Tuladhar, B R; Sanger, G J

    2007-01-01

    Background and purpose: The neuromedin U (NMU) receptors, NMU1 and NMU2, are expressed in the gut but their functions are unclear. This study explores the role of NMU in gastrointestinal motility. Experimental approach: The effects of NMU were examined in the forestomach and colon isolated from NMU2R wild-type and NMU2R-/- (knockout) mice, looking for changes in muscle tension and in nerve-mediated responses evoked by electrical field stimulation (EFS), and in models of peristalsis in mouse colon and faecal pellet transit in guinea-pig colon. Key results: In the mouse forestomach, NMU (1 nM-10 μM) concentration-dependently induced muscle contraction, in the presence of tetrodotoxin and atropine, in preparations from both wild-type and NMU2R-/- mice (pEC50: 7.9, 7.6, Emax: 0.26, 0.20g tension, respectively, n=8 each concentration). The same concentrations of NMU had no consistent effects on the responses to EFS (n=8). In the mouse colon, NMU (0.1 nM-1 μM) had no significant effect on baseline muscle tension (n=8), but concentration-dependently potentiated EFS-evoked contractions in preparations from both wild-type and NMU2R-/- mice, pEC50: 8.1, 7.8, Emax: 24%, 21%, respectively, n=6-11. NMU (0.01 nM-0.1 μM, n=5-7) concentration-dependently decreased the interval between waves of peristalsis in the mouse colon (pEC50: 8.8) and increased the rate at which a faecal pellet moved along the guinea-pig colon. Conclusions and implications: These results demonstrate that NMU exerts colon-specific, nerve-mediated, prokinetic activity, via a pathway involving activation of NMU1 receptors. This suggests that this receptor may represent a molecular target for the treatment of intestinal motility disorders. PMID:17211455

  12. Antioxidant activity of polyphenolic compounds isolated from ethyl-acetate fraction of Acacia hydaspica R. Parker.

    Science.gov (United States)

    Afsar, Tayyaba; Razak, Suhail; Shabbir, Maria; Khan, Muhammad Rashid

    2018-01-25

    Acacia hydaspica belongs to family leguminosae possess antioxidant, anti-inflammatory and anticancer activities. During our search for antioxidant compounds from A. hydaspica, we carried out bioassay guided fractionation and obtained antioxidant compounds with free radical scavenging activity. The polyphenol compounds in the plant extract of A. hydaspica were isolated by combination of different chromatographic techniques involving vacuum liquid chromatography and medium pressure liquid chromatography. The structural heterogeneity of isolated compounds was characterized by high pressure liquid chromatography, MS-ESI and NMR spectroscopic analyses. The antioxidant potential of isolated compounds has been investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging potential, hydroxyl radical scavenging potential, ferric reducing/antioxidant power (FRAP) model systems and total antioxidant capacity measurement. The isolated compounds show the predominance of signals representative of 7-O-galloyl catechins, catechins and methyl gallate. Flash chromatographic separation gives 750 mg of 7-O galloyl catechin, 400 mg of catechin and 150 mg of methyl gallate from 4 g loaded fraction on ISCO. Results revealed that C1 was the most potent compound against DPPH (EC 50 1.60 ± 0.035 µM), nitric oxide radical (EC 50 6 ± 0.346 µM), showed highest antioxidant index (1.710 ± 0.04) and FRAP [649.5 ± 1.5 µM Fe(II)/g] potency at 12.5 µM dose compared to C2, C3 and standard reference, whereas C3 showed lower EC 50 values (4.33 ± 0.618 µM) in OH radical scavenging assay. Present research reports for the first time the antioxidant activity of polyphenolic compounds of A. hydaspica. Result showed good resolution and separation from other constituents of extract and method was found to be simple and precise. The isolation of catechin from this new species could provide a varied opportunity to obtain large quantities of catechin and catechin

  13. Cloxyquin (5-chloroquinolin-8-ol) is an activator of the two-pore domain potassium channel TRESK.

    Science.gov (United States)

    Wright, Paul D; Weir, Gregory; Cartland, Jamie; Tickle, David; Kettleborough, Catherine; Cader, M Zameel; Jerman, Jeff

    2013-11-15

    TRESK is a two-pore domain potassium channel. Loss of function mutations have been linked to typical migraine with aura and due to TRESK’s expression pattern and role in neuronal excitability it represents a promising therapeutic target. We developed a cell based assay using baculovirus transduced U20S cells to screen for activators of TRESK. Using a thallium flux system to measure TRESK channel activity we identified Cloxyquin as a novel activator. Cloxyquin was shown to have an EC50 of 3.8 μM in the thallium assay and displayed good selectivity against other potassium channels tested. Activity was confirmed using whole cell patch electrophysiology, with Cloxyquin causing a near two fold increase in outward current. The strategy presented here will be used to screen larger compound libraries with the aim of identifying novel chemical series which may be developed into new migraine prophylactics.

  14. A protein chip membrane-capture assay for botulinum neurotoxin activity

    International Nuclear Information System (INIS)

    Marconi, Severine; Ferracci, Geraldine; Berthomieu, Maelys; Kozaki, Shunji; Miquelis, Raymond; Boucraut, Jose; Seagar, Michael

    2008-01-01

    Botulinum neurotoxins A and B (BoNT/A and B) are neuromuscular blocking agents which inhibit neurotransmission by cleaving the intra-cellular presynaptic SNARE proteins SNAP-25 and VAMP2, localized respectively in plasma membrane and synaptic vesicles. These neurotoxins are both dangerous pathogens and powerful therapeutic agents with numerous clinical and cosmetic applications. Consequently there is a need for in vitro assays of their biological activity to screen for potential inhibitors and to replace the widely used in vivo mouse assay. Surface plasmon resonance (SPR) was used to measure membrane vesicle capture by antibodies against SNAP-25 and VAMP2. Substrate cleavage by BoNTs modified capture providing a method to assay toxin activity. Firstly using synaptic vesicles as a substrate, a comparison of the EC 50 s for BoNT/B obtained by SPR, ELISA or flow cytometry indicated similar sensitivity although SPR assays were more rapid. Sonication of brain or neuronal cultures generated plasma membrane fragments with accessible intra-cellular epitopes adapted to measurement of BoNT/A activity. SPR responses were proportional to antigen concentration permitting detection of as little as 4 pM SNAP-25 in crude lysates. BoNT/A activity was assayed using monoclonal antibodies that specifically recognize a SNAP-25 epitope generated by the proteolytic action of the toxin. Incubation of intact primary cultured neurons with BoNT/A yielded an EC 50 of 0.5 pM. The SPR biosensor method was sensitive enough to monitor BoNT/A and B activity in cells cultured in a 96-well format providing an alternative to experimental animals for toxicological assays

  15. Synthesis and Antifungal Activity of Novel Sulfone Derivatives Containing 1,3,4-Oxadiazole Moieties

    Directory of Open Access Journals (Sweden)

    Maoguo Tong

    2011-11-01

    Full Text Available A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC50 values of 5.21 μg/mL, 8.25 µg/mL, 8.03 µg/mL, and 21.00 µg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.

  16. The orphan G protein-coupled receptor GPR139 is activated by the peptides

    DEFF Research Database (Denmark)

    Jensen, Anne Cathrine Nøhr; Shehata, Mohamed A; Hauser, Alexander S

    2017-01-01

    GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well...... cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH1-9. Further studies are needed to determine the functional relevance...

  17. Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

    Science.gov (United States)

    Ebiloma, Godwin Unekwuojo; Igoli, John Ogbaji; Katsoulis, Evangelos; Donachie, Anne-Marie; Eze, Anthonius; Gray, Alexander Ian; de Koning, Harry P

    2017-04-18

    Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58µg/mL. None of the isolated compounds displayed toxicity

  18. Chemical constituents and free radical scavenging activity of corn pollen collected from Apis mellifera hives compared to floral corn pollen at Nan, Thailand

    Directory of Open Access Journals (Sweden)

    Chantarudee Atip

    2012-04-01

    Full Text Available Abstract Background Bee pollen is composed of floral pollen mixed with nectar and bee secretion that is collected by foraging honey (Apis sp. and stingless bees. It is rich in nutrients, such as sugars, proteins, lipids, vitamins and flavonoids, and has been ascribed antiproliferative, anti-allergenic, anti-angiogenic and free radical scavenging activities. This research aimed at a preliminary investigation of the chemical constituents and free radical scavenging activity in A. mellifera bee pollen. Methods Bee pollen was directly collected from A. mellifera colonies in Nan province, Thailand, in June, 2010, whilst floral corn (Zea mays L. pollen was collected from the nearby corn fields. The pollen was then sequentially extracted with methanol, dichloromethane (DCM and hexane, and each crude extract was tested for free radical scavenging activity using the DPPH assay, evaluating the percentage scavenging activity and the effective concentration at 50% (EC50. The most active crude fraction from the bee pollen was then further enriched for bioactive components by silica gel 60 quick and adsorption or Sephadex LH-20 size exclusion chromatography. The purity of all fractions in each step was observed by thin layer chromatography and the bioactivity assessed by the DPPH assay. The chemical structures of the most active fractions were analyzed by nuclear magnetic resonance. Results The crude DCM extract of both the bee corn pollen and floral corn pollen provided the highest active free radical scavenging activity of the three solvent extracts, but it was significantly (over 28-fold higher in the bee corn pollen (EC50 = 7.42 ± 0.12 μg/ml, than the floral corn pollen (EC50 = 212 ± 13.6% μg/ml. After fractionation to homogeneity, the phenolic hydroquinone and the flavone 7-O-R-apigenin were found as the minor and major bioactive compounds, respectively. Bee corn pollen contained a reasonably diverse array of nutritional components, including

  19. Chemical constituents and free radical scavenging activity of corn pollen collected from Apis mellifera hives compared to floral corn pollen at Nan, Thailand

    Science.gov (United States)

    2012-01-01

    Background Bee pollen is composed of floral pollen mixed with nectar and bee secretion that is collected by foraging honey (Apis sp.) and stingless bees. It is rich in nutrients, such as sugars, proteins, lipids, vitamins and flavonoids, and has been ascribed antiproliferative, anti-allergenic, anti-angiogenic and free radical scavenging activities. This research aimed at a preliminary investigation of the chemical constituents and free radical scavenging activity in A. mellifera bee pollen. Methods Bee pollen was directly collected from A. mellifera colonies in Nan province, Thailand, in June, 2010, whilst floral corn (Zea mays L.) pollen was collected from the nearby corn fields. The pollen was then sequentially extracted with methanol, dichloromethane (DCM) and hexane, and each crude extract was tested for free radical scavenging activity using the DPPH assay, evaluating the percentage scavenging activity and the effective concentration at 50% (EC50). The most active crude fraction from the bee pollen was then further enriched for bioactive components by silica gel 60 quick and adsorption or Sephadex LH-20 size exclusion chromatography. The purity of all fractions in each step was observed by thin layer chromatography and the bioactivity assessed by the DPPH assay. The chemical structures of the most active fractions were analyzed by nuclear magnetic resonance. Results The crude DCM extract of both the bee corn pollen and floral corn pollen provided the highest active free radical scavenging activity of the three solvent extracts, but it was significantly (over 28-fold) higher in the bee corn pollen (EC50 = 7.42 ± 0.12 μg/ml), than the floral corn pollen (EC50 = 212 ± 13.6% μg/ml). After fractionation to homogeneity, the phenolic hydroquinone and the flavone 7-O-R-apigenin were found as the minor and major bioactive compounds, respectively. Bee corn pollen contained a reasonably diverse array of nutritional components, including biotin (56.7 μg/100

  20. Platypus and opossum calcitonins exhibit strong activities, even though they belong to mammals.

    Science.gov (United States)

    Yamashita, Teruhito; Udagawa, Nobuyuki; Thirukonda, Gnanasagar Janardhanan; Uehara, Shunsuke; Yamauchi, Hirose; Suzuki, Nobuo; Li, Feng; Kobayashi, Yasuhiro; Takahashi, Naoyuki

    2017-05-15

    In mammalian assay systems, calcitonin peptides of non-mammalian species exhibit stronger activity than those of mammals. Recently, comparative analyses of a wide-range of species revealed that platypus and opossum, which diverged early from other mammals, possess calcitonins that are more similar in amino acid sequence to those of non-mammals than mammals. We herein determined whether platypus and opossum calcitonins exhibit similar biological activities to those of non-mammalian calcitonins using an assay of actin ring formation in mouse osteoclasts. We also compared the dose-dependent effects of each calcitonin on cAMP production in osteoclasts. Consistent with the strong similarities in their primary amino acid sequences, platypus and opossum calcitonins disrupted actin rings with similar efficacies to that of salmon calcitonin. Human calcitonin exhibited the weakest inhibitory potency and required a 100-fold higher concentration (EC 50 =3×10 -11 M) than that of salmon calcitonin (EC 50 =2×10 -13 M). Platypus and opossum calcitonins also induced cAMP production in osteoclast cultures with the same efficacies as that of salmon calcitonin. Thus, platypus and opossum calcitonins exhibited strong biological activities, similar to those of the salmon. In addition, phylogenetic analysis revealed that platypus and opossum calcitonins clustered with the salmon-type group but not human- or porcine-type group. These results suggest that platypus and opossum calcitonins are classified into the salmon-type group, in terms of the biological activities and amino acid sequences. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Antioxidants L-carnitine and D-methionine modulate neuronal activity through GABAergic inhibition.

    Science.gov (United States)

    Wu, Calvin; Gopal, Kamakshi V; Moore, Ernest J; Gross, Guenter W

    2014-07-01

    Antioxidants are well known for their neuroprotective properties against reactive oxygen species in cortical neurons and auditory cells. We recently identified L-carnitine and D-methionine to be among agents that provide such protection. Here, we investigated their neuronal modulatory actions. We used cultured neuronal networks grown on microelectrode arrays to assess the effects of L-carnitine and D-methionine on network function. Spike production and burst properties of neuronal networks were used as parameters to monitor pharmacological responses. L-Carnitine and D-methionine reduced spike activity with 100% efficacy with EC50 values of 0.22 (± 0.01) mM and 1.06 (± 0.05) mM, respectively. In the presence of 1.0-40 μM of the GABAA antagonist bicuculline, the sigmoidal concentration-response curves of both compounds exhibited stepwise shifts, without a change in efficacy. Under a maximal bicuculline concentration of 40 μM, the EC50 increased to 3.57 (± 0.26) mM for L-carnitine and to 10.52 (± 0.97) mM for D-methionine, more than a tenfold increase. The agonist-antagonist interactions with bicuculline were estimated by Lineweaver-Burk plot analyses to be competitive, corroborated by the computed dissociation constants of bicuculline. For both compounds, the effects on the network burst pattern, activity reversibility, and bicuculline antagonism resembled that elicited by the GABAA agonist muscimol. We showed that the antioxidants L-carnitine and D-methionine modulate cortical electrical spike activity primarily through GABAA receptor activation. Our findings suggest the involvement of GABAergic mechanisms that perhaps contribute to the protective actions of these compounds.

  2. Pharmacological characterisation and inhibitory effects of (2R,3R,4S,5R)-2-(6-amino-2-{[(1S)-2-hydroxy-1-(phenylmethyl)ethyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3,4-furandiol, a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity.

    Science.gov (United States)

    Bevan, Nicola; Butchers, Peter R; Cousins, Rick; Coates, Jill; Edgar, Emma V; Morrison, Val; Sheehan, Michael J; Reeves, Julian; Wilson, David J

    2007-06-14

    The pharmacological properties of the novel ligand, (2R,3R,4S,5R)-2-(6-amino-2-{[(1S)-2-hydroxy-1-(phenylmethyl)ethyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3,4-furandiol (I), at the human adenosine receptors were investigated using Chinese hamster ovary cell lines recombinantly expressing these receptors. Functional studies were performed using a cyclic AMP-coupled reporter gene system. Binding studies were performed using membranes from these cells. The effects of ligand (I) were also determined on functional responses of human neutrophils and eosinophils. Ligand (I) had a high affinity for the adenosine A(2A) receptor (pKi 7.8+/-0.2) and was a potent agonist at this receptor (pEC(50) 9.0+/-0.2). Ligand (I) had a similar affinity for the adenosine A(3) receptor (pKi 7.8+/-0.1) but displayed no agonist activity, acting instead as a competitive antagonist (pA(2) 8.3+/-0.04). Ligand (I) had lower affinity for adenosine A(1) and A(2B) receptors (pKiactivity at these receptors (pEC(50) 7.1 at both receptors). Ligand (I) was a potent inhibitor of the generation of reactive oxygen species from human neutrophils and eosinophils (pEC(50) 9.7+/-0.1 and 9.4+/-0.2 respectively). The inhibitory effect of ligand (I) on the release of reactive oxygen species from neutrophils was antagonised competitively by the adenosine A(2A) receptor antagonist 9-chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) with a pA(2) value (10.03+/-0.44) consistent with an effect on adenosine A(2A) receptors. Ligand (I) also inhibited the release of granule proteins from neutrophils and eosinophils (pEC(50) 8.7 and 8.9 respectively), albeit less potently than as an inhibitor of reactive oxygen species generation. In summary, ligand (I) is a potent and selective agonist for the adenosine A(2A) receptor and a competitive antagonist at the adenosine A(3) receptor. Ligand (I) has potent anti-inflammatory effects on human

  3. Binding of curcumin and its long chain derivatives to the activator binding domain of novel protein kinase C.

    Science.gov (United States)

    Majhi, Anjoy; Rahman, Ghazi M; Panchal, Shyam; Das, Joydip

    2010-02-15

    Protein kinase C (PKC) is a family of serine/threonine kinases that play a central role in cellular signal transduction. The second messenger diacylglycerol having two long carbon chains acts as the endogenous ligand for the PKCs. Polyphenol curcumin, the active constituent of Curcuma longa is an anti-cancer agent and modulates PKC activity. To develop curcumin derivatives as effective PKC activators, we synthesized several long chain derivatives of curcumin, characterized their absorption and fluorescence properties and studied their interaction with the activator binding second cysteine-rich C1B subdomain of PKCdelta, PKCepsilon and PKCtheta. Curcumin (1) and its C16 long chain analog (4) quenched the intrinsic fluorescence of PKCdeltaC1B, PKCepsilonC1B and PKCthetaC1B in a manner similar to that of PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA). The EC(50)s of the curcumin derivatives for fluorescence quenching varied in the range of 4-11 microM, whereas, EC(50)s for TPA varied in the range of 3-6 microM. Fluorescence emission maxima of 1 and 4 were blue shifted and the fluorescence anisotropy values were increased in the presence of the C1B domains in a manner similar to that shown by the fluorescent analog of TPA, sapintoxin-D, confirming that they were bound to the proteins. Molecular docking of 1 and 4 with novel PKC C1B revealed that both the molecules form hydrogen bonds with the protein residues. The present result shows that curcumin and its long chain derivatives bind to the C1B subdomain of novel PKCs and can be further modified structurally to improve its binding and activity. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. Ligand determinants of fatty acid activation of the pronociceptive ion channel TRPA1

    Directory of Open Access Journals (Sweden)

    William John Redmond

    2014-01-01

    Full Text Available Background and purpose. Arachidonic acid (AA and its derivatives are important modulators of cellular signalling. The transient receptor potential cation channel subfamily A, member 1 (TRPA1 is a cation channel with important functions in mediating cellular responses to noxious stimuli and inflammation. There is limited information about the interactions between AA itself and TRPA1, so we investigated the effects of AA and key ethanolamide and amino acid/neurotransmitter derivatives of AA on hTRPA1.Experimental approach. HEK 293 cells expressing hTRPA1 were studied by measuring changes in intracellular calcium ([Ca]i with a fluorescent dye and by standard whole cell patch clamp recordings.Key results. AA (30 μM increased fluorescence in hTRPA1 expressing cells by 370% (notional EC50 13 μM. The covalent TRPA1 agonist cinnamaldehyde (300 μM increased fluorescence by 430% (EC50, 11 μM. Anandamide (230% and N-arachidonoyl tyrosine (170% substantially activated hTRPA1 at 30 μM, however, N-arachidonoyl conjugates of glycine and taurine were less effective while N-acyl conjugates of 5-HT did not affect hTRPA1. Changing the acyl chain length or the number and position of double bonds reduced fatty acid efficacy at hTRPA1. Mutant hTRPA1 (Cys621, Cys641 and Cys665 changed to Ser could be activated by AA (100 μM, 40% of wild type but not by cinnamaldehyde (300 μM.Conclusions and implications. AA is a more potent activator of TRPA1 than its ethanolamide or amino acid/neurotransmitter derivatives and acts via a mechanism distinct from that of cinnamaldehyde, further underscoring the likelyhood of multiple pharmacologically exploitable sites on hTRPA1.

  5. Influence of cations on activity and distribution of protein kinase C in S49 lymphoma cells

    International Nuclear Information System (INIS)

    Brunton, L.; Watson, M.; Schultz, M.; Trejo, J.; Speizer, L.

    1987-01-01

    In S49 lymphoma cells, the distribution of protein kinase C (PKC) between soluble and membrane fractions can be regulated by the concentration of Ca ++ in the homogenization buffer. When cells are fractionated with 10μM Ca ++ and low Mg ++ (0.3mM), PKC is largely (56%) membrane-bound. Mg ++ inhibits this effect of Ca ++ by 75%; the EC 50 for Mg ++ reducing the translocation induced by 10μM Ca ++ is 1mM, as detected by binding of [ 3 H] phorbol dibutyrate ([ 3 H]PDB). Other divalent cations have different effects. When Cu ++ (1mM) is included in the homogenization buffer, both the enzymic activity of PKC and its capacity to bind [ 3 H]PDB are lost in both the cytosolic and membrane fractions. Cd ++ and Zn ++ (at 1mM) also inhibit the binding of [ 3 H]PDB to PKC in cytosolic fractions. K + , Li + , Co ++ and Mn ++ at 1mM do not mimic these effects. With Ca ++ at 500μM, the EC 50 for inhibition by Cu ++ of [ 3 H]PDB binding and enzymic activity of PKC are 25μM and 75μM, respectively. These effects of Cu ++ are also noticeable when the cation is added to intact S49 cells. The effect of Cu ++ on PKC is only relatively specific: [Cu ++ ] ≥ 100μM inhibits the activity of cyclic AMP-dependent protein kinase in vitro. Knowledge of these effects of heavy metals on PKC may prove helpful in manipulation of the enzyme pharmacologically as well as in determining the role of PKC in the cellular responses to heavy metals

  6. Appraisal of Total Phenol, Flavonoid Contents, and Antioxidant Potential of Folkloric Lannea coromandelica Using In Vitro and In Vivo Assays.

    Science.gov (United States)

    Kumar, Tekeshwar; Jain, Vishal

    2015-01-01

    The aim of this study was to determine the impending antioxidant properties of different extracts of crude methanolic extract (CME) of leaves of Lannea coromandelica (L. coromandelica) and its two ethyl acetate (EAF) and aqueous (AqF) subfractions by employing various established in vitro systems and estimation of total phenolic and flavonoid content. The results showed that extract and fractions possessed strong antioxidant activity in vitro and among them, EAF had the strongest antioxidant activity. EAF was confirmed for its highest phenolic content, total flavonoid contents, and total antioxidant capacity. The EAF was found to show remarkable scavenging activity on 2,2-diphenylpicrylhydrazyl (DPPH) (EC50 63.9 ± 0.64 µg/mL), superoxide radical (EC50 8.2 ± 0.12 mg/mL), and Fe(2+) chelating activity (EC50 6.2 ± 0.09 mg/mL). Based on our in vitro results, EAF was investigated for in vivo antioxidant assay. Intragastric administration of the EAF can significantly increase levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels, and decrease malondialdehyde (MDA) content in the liver and kidney of CCl4-intoxicated rats. These new evidences show that L. coromandelica bared antioxidant activity.

  7. Appraisal of Total Phenol, Flavonoid Contents, and Antioxidant Potential of Folkloric Lannea coromandelica Using In Vitro and In Vivo Assays

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    Tekeshwar Kumar

    2015-01-01

    Full Text Available The aim of this study was to determine the impending antioxidant properties of different extracts of crude methanolic extract (CME of leaves of Lannea coromandelica (L. coromandelica and its two ethyl acetate (EAF and aqueous (AqF subfractions by employing various established in vitro systems and estimation of total phenolic and flavonoid content. The results showed that extract and fractions possessed strong antioxidant activity in vitro and among them, EAF had the strongest antioxidant activity. EAF was confirmed for its highest phenolic content, total flavonoid contents, and total antioxidant capacity. The EAF was found to show remarkable scavenging activity on 2,2-diphenylpicrylhydrazyl (DPPH (EC50 63.9 ± 0.64 µg/mL, superoxide radical (EC50 8.2 ± 0.12 mg/mL, and Fe2+ chelating activity (EC50 6.2 ± 0.09 mg/mL. Based on our in vitro results, EAF was investigated for in vivo antioxidant assay. Intragastric administration of the EAF can significantly increase levels of superoxide dismutase (SOD, catalase (CAT, glutathione (GSH, and glutathione peroxidase (GSH-Px levels, and decrease malondialdehyde (MDA content in the liver and kidney of CCl4-intoxicated rats. These new evidences show that L. coromandelica bared antioxidant activity.

  8. The Satiety Signaling Neuropeptide Perisulfakinin Inhibits the Activity of Central Neurons Promoting General Activity

    Science.gov (United States)

    Wicher, Dieter; Derst, Christian; Gautier, Hélène; Lapied, Bruno; Heinemann, Stefan H.; Agricola, Hans-Jürgen

    2007-01-01

    The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM) due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage. PMID:18946521

  9. The satiety signaling neuropeptide perisulfakinin inhibits the activity of central neurons promoting general activity

    Directory of Open Access Journals (Sweden)

    Dieter Wicher

    2007-12-01

    Full Text Available The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR, we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH: PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage.

  10. Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

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    Bao-Ju Li

    2013-11-01

    Full Text Available A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50 of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure–activity relationship, comparative molecular field analysis (CoMFA was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study.

  11. Design, synthesis, antifungal activities and 3D-QSAR of new N,N'-diacylhydrazines containing 2,4-dichlorophenoxy moiety.

    Science.gov (United States)

    Sun, Na-Bo; Shi, Yan-Xia; Liu, Xing-Hai; Ma, Yi; Tan, Cheng-Xia; Weng, Jian-Quan; Jin, Jian-Zhong; Li, Bao-Ju

    2013-11-01

    A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50) of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study.

  12. Activity of andrographolide against dengue virus.

    Science.gov (United States)

    Panraksa, Patcharee; Ramphan, Suwipa; Khongwichit, Sarawut; Smith, Duncan R

    2017-03-01

    Dengue is the most prevalent arthropod-transmitted viral illness of humans, with an estimated 100 million symptomatic infections occurring each year and more than 2.5 billion people living at risk of infection. There are no approved antiviral agents against dengue virus, and there is only limited introduction of a dengue vaccine in some countries. Andrographolide is derived from Andrographis paniculata, a medicinal plant traditionally used to treat a number of conditions including infections. The antiviral activity of andrographolide against dengue virus (DENV) serotype 2 was evaluated in two cell lines (HepG2 and HeLa) while the activity against DENV 4 was evaluated in one cell line (HepG2). Results showed that andrographolide had significant anti-DENV activity in both cell lines, reducing both the levels of cellular infection and virus output, with 50% effective concentrations (EC 50 ) for DENV 2 of 21.304 μM and 22.739 μM for HepG2 and HeLa respectively. Time of addition studies showed that the activity of andrographolide was confined to a post-infection stage. These results suggest that andrographolide has the potential for further development as an anti-viral agent for dengue virus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Effect of radiation processing on the antioxidant activity of Sage and Cinnamon

    International Nuclear Information System (INIS)

    El-Niley, H. F. G.; Farag, M. D. H.

    2012-12-01

    In the present study, the effect of radiation processing on dried sage leaves and cinnamon barks samples were carried out at dose level of 25 kGy. Total phenolic content was determined in the extracts of these herbs alongside the antioxidant properties of their methanoic extracts were assessed using reducing power assay and by DPPH radical test within an extract concentration range 2.5 to 40 mg/ml of methanol. The result showed the total phenolic compounds were increased by 11.18% and 10.19% for irradiated sage and cinnamon, respectively. The values of EC 50 estimated from the results of reducing power assay and DPPH radical test showed the sage extracts had higher antioxidant activity tham cinnamon extracts. In summary, gamma- irradiation of dried sage leaves and cinnamon barks was found to be significantly increase the antioxidant properties of dried sage leaves and cinnamon barks but also enhanced the antioxidant properties, to some extent. (Author)

  14. Critical appraisal of respirometric methods for metal inhibition on activated sludge

    International Nuclear Information System (INIS)

    Cokgor, E. Ubay; Ozdemir, S.; Karahan, O.; Insel, G.; Orhon, D.

    2007-01-01

    This paper evaluates the merit of oxygen uptake rate measurements for the assessment of metal inhibition on activated sludge. For this purpose, experiments are conducted to calculate EC 50 levels of nickel and hexavalent chromium using the ISO 8192 procedure, yielding results that are highly variable and difficult to correlate, depending on the type of substrate and the initial food to microorganism ratio. Similar experiments based on continuous respirometric measurements to give the entire oxygen uptake rate profile provide a much better insight on the impact of inhibition on different biochemical processes taking place in the reactor. The results indicate that percent reduction of the amount of dissolved oxygen utilized after an appropriate reaction time is a much better index for the assessment of the inhibitory effects

  15. Synthesis of analogues of Congo red and evaluation of their anti-prion activity.

    Science.gov (United States)

    Sellarajah, Shane; Lekishvili, Tamuna; Bowring, Claire; Thompsett, Andrew R; Rudyk, Helene; Birkett, Christopher R; Brown, David R; Gilbert, Ian H

    2004-10-21

    No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

  16. Unified basis for the respirometric evaluation of inhibition for activated sludge.

    Science.gov (United States)

    Insel, Guclu; Karahan, Ozlen; Ozdemir, Seda; Pala, Llke; Katipoğlu, Tugce; Cokgör, Emine Ubay; Orhon, Derin

    2006-01-01

    This paper explores the merit of the oxygen uptake rate (OUR) profile obtained by means of respirometry as the basic mechanistic instrument for evaluating activated sludge inhibition. Experimental OUR data are generated using the synthetic peptone-based substrate and inhibition is tested with 60 mg/L hexavalent chromium and 33 mg/L nickel additions, corresponding to EC50 levels determined using the standard ISO 8192 procedure. Experimental results are evaluated by model calibration using ASM1 modified for dual hydrolysis and ASM3 modified for simultaneous growth. Model evaluations indicate that inhibition affects not only growth, but also other significant microbial mechanisms such as substrate storage and hydrolysis, leading to conclude that the proposed approach will enable to visualize the overall impact of the inhibitory compound on every stage of substrate biodegradation, through inspection and evaluation of the entire OUR profile.

  17. Relationship between Antioxidant and Anticancer Activity of Trihydroxyflavones

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    Ignas Grigalius

    2017-12-01

    Full Text Available Plant polyphenols have been highlighted not only as chemopreventive, but also as potential anticancer substances. Flavones are a subclass of natural flavonoids reported to have an antioxidant and anticancer activity. The aim of our study was to evaluate antioxidant and anticancer activity of seventeen trihydroxyflavone derivatives, including apigenin (API and baicalein (BCL. Also, we wanted to find out if there is a correlation between those two effects. Cell growth inhibition testing was carried out using MTT assay in three different human cancer cell lines: lung (A549, breast (MCF-7 and brain epithelial (U87. Antioxidant activity was determined by the DPPH radical scavenging method. Thirteen trihydroxyflavones possessed anticancer activity against at least one tested cancer cell line. They were more active against the MCF-7 cell line, and the lowest activity was determined against the U87 cell line. The majority of compounds inhibited cancer cell growth at EC50 values between 10–50 µM. The most active compound was 3’,4’,5-trihydroxyflavone 7, especially against A549 and MCF-7 cell lines. The correlation between anti-proliferative and antioxidant activity was only moderate, and it was determined for A549 and U87 cancer cell lines. The most important fragment for those two effects is the ortho-dihydroxy group in ring B. Conclusions. Trihydroxyflavones demonstrated anticancer activity. Further and more detailed studies should to be carried out to estimate the structure–activity relationship of these compounds.

  18. Isolation and molecular identification of a UV-resistant strain of Dietzia maris and antioxidant activity of pigment

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    Narges Zamanian

    2016-09-01

    Full Text Available Introduction: The ability of radioresistant bacteria to survive high levels of UV radiation has been linked to their strong DNA repair systems and ability to produce primary and secondary metabolic products. The biosynthesis of pigments provides an opportunity for bacteria to live in radiation-rich environment. Recent radiation-responsive pigments are used commercially as food colorants, anticancer drugs, as well as antibiotics and for cosmetic purposes. Materials and methods: Soil sample of Omidiyeh city was collected during the spring of 2014 and UV-resistant strain was isolated after primary and secondary screening. Then it was identified by molecular methods (16S rRNA gene sequencing. Antioxidant activity of pigment was evaluated by 2,2 -diphenyl-1-picryl hydrazyl (DPPH and the reducing power of pigments were analyzed by ferric chloride. Results: In this present study, new UV-resistant strain NM2 was isolated and by comparison of these 16S rRNA gene sequences to public database using the BLAST, the genus and species of the isolate was identified as Dietzia maris with 99% similarity. Extraction of pigment from isolated strain was carried out by methanol and acetone as solvents. The spectrum is characterized by maximum peak at 473 nm for pigment of NM2 strain. Antioxidant activity and the reducing ability of pigments increased by increasing their concentrations. NM2 strain pigment showed EC50 concentration of 3.30 mg/ml for DPPH free radical scavenging activity, and EC50 concentration of 28.46 µg/ml for reducing power. Discussion and conclusion: Isolation of natural resources of pigment is very important with high anti-oxidant activity. In the current study, pigment of UV-resistant bacteria demonstrated a strong antioxidant activity in vitro and pigment of these bacteria could play an important role in UV tolerance. Pigment of UV-resistant bacteria may be an appropriate source for antioxidative-related functional foods and the pharmaceutical

  19. In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.

    Science.gov (United States)

    Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Dos Santos, Jamyle Andrade Ferreira; Moreira, Diogo Rodrigo Magalhães; Nogueira, Renata Campos; Tomassini, Therezinha Coelho Barbosa; Ribeiro, Ivone Maria; de Souza, Claudia Valeria Campos; Ribeiro Dos Santos, Ricardo; Soares, Milena Botelho Pereira

    2015-10-15

    The current treatment of Chagas disease, endemic in Latin America and emerging in several countries, is limited by the frequent side effects and variable efficacy of benznidazole. Natural products are an important source for the search for new drugs. Considering the great potential of natural products as antiparasitic agents, we investigated the anti-Trypanosoma cruzi activity of a concentrated ethanolic extract of Physalis angulata (EEPA). Cytotoxicity to mammalian cells was determined using mouse peritoneal macrophages. The antiparasitic activity was evaluated against axenic epimastigote and bloodstream trypomastigote forms of T. cruzi, and against amastigote forms using T. cruzi-infected macrophages. Cell death mechanism was determined in trypomastigotes by flow cytometry analysis after annexin V and propidium iodide staining. The efficacy of EEPA was examined in vivo in an acute model of infection by monitoring blood parasitaemia and survival rate 30 days after treatment. The effect against trypomastigotes of EEPA and benznidazole acting in combination was evaluated. EEPA effectively inhibits the epimastigote growth (IC50 2.9 ± 0.1 µM) and reduces bloodstream trypomastigote viability (EC50 1.7 ± 0.5 µM). It causes parasite cell death by necrosis. EEPA impairs parasite infectivity as well as amastigote development in concentrations noncytotoxic to mammalian cells. In mice acutely-infected with T. cruzi, EEPA reduced the blood parasitaemia in 72.7%. When combined with benznidazole, EEPA showed a synergistic anti-T. cruzi activity, displaying CI values of 0.8 ± 0.07 at EC50 and 0.83 ± 0.1 at EC90. EEPA has antiparasitic activity against T. cruzi, causing cell death by necrosis and showing synergistic activity with benznidazole. These findings were reinforced by the observed efficacy of EEPA in reducing parasite load in T. cruzi-mice. Therefore, this represents an important source of antiparasitic natural products. Copyright © 2015 Elsevier GmbH. All rights

  20. In vitro anti-herpes simplex virus-2 activity of Salvia desoleana Atzei & V. Picci essential oil.

    Science.gov (United States)

    Cagno, Valeria; Sgorbini, Barbara; Sanna, Cinzia; Cagliero, Cecilia; Ballero, Mauro; Civra, Andrea; Donalisio, Manuela; Bicchi, Carlo; Lembo, David; Rubiolo, Patrizia

    2017-01-01

    Salvia desoleana Atzei & V. Picci is an indigenous species in Sardinia island used in folk medicine to treat menstrual, digestive and central nervous system diseases. Nowadays, it is widely cultivated for the pleasant smell of its essential oil (EO), whose antimicrobial and antifungal activities have already been screened. This study evaluated the in vitro anti-Herpes Simplex Virus-2 (HSV-2) activity of S. desoleana EO, fractions and main components: linalyl acetate, alpha terpinyl acetate, and germacrene D. Phytochemical composition of S. desoleana EO was studied by GC-FID/MS analysis and the active fraction(s) and/or compounds in S. desoleana EO were identified with a bioassay-guided fractionation procedure through in vitro assays on cell viability and HSV-2 and RSV inhibition. S. desoleana EO inhibits both acyclovir sensitive and acyclovir resistant HSV-2 strains with EC50 values of 23.72 μg/ml for the former and 28.57 μg/ml for the latter. Moreover, a significant suppression of HSV-2 replication was observed with an EC50 value of 33.01 μg/ml (95% CI: 26.26 to 41.49) when the EO was added post-infection. Among the fractions resulting from flash column chromatography on silica gel, the one containing 54% of germacrene D showed a similar spectrum of activity of S. desoleana EO with a stronger suppression in post-infection stage. These results indicated that S. desoleana EO can be of interest to develop new and alternative anti-HSV-2 products active also against acyclovir-resistant HSV-2 strains.

  1. Prevention of biofilm growth on man-made surfaces: evaluation of antialgal activity of two biocides and photocatalytic nanoparticles.

    Science.gov (United States)

    Gladis, F; Eggert, A; Karsten, U; Schumann, R

    2010-01-01

    As algal growth on man-made surfaces impacts their appearance, biocides and surfaces with self-cleaning properties are widely used in the building and paint industries. The objective of this study was to evaluate the antialgal activity of two biocides (triazine and isothiazoline) and photocatalytic nanoparticles of zinc oxide (20-60 nm). An aeroterrestrial green, microalgal strain of the genus Stichococcus was chosen as the test organism. By comparing a set of different structural and physiological performance parameters, lethal and also sublethal (chronic) effects were determined. Even though the herbicide triazine effectively inhibited growth (EC50 = 1.6 micromol l(-1)) and photosynthetic performance, structural properties (eg membrane integrity) were unaffected at the EC100 (250 micromol l(-1)), hence this herbicide did not kill the algal cells. In contrast, and due to their multiple modes of action, isothiazoline and the photocatalytic nanoparticles (the latter activated with low UV radiation) severely impacted all performance and structural parameters.

  2. Free radical scavenging activity of ethanolic extracts from herbs and spices commercialized in Brazil

    Directory of Open Access Journals (Sweden)

    Lilian Regina Barros Mariutti

    2008-12-01

    Full Text Available Ethanolic extracts from 23 different dried herbs and spices commercialized in Brazil were investigated for their free radical scavenging properties using the stable free radicals 2,2'-diphenyl-β-picrylhydrazyl (DPPH• and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+, and Trolox as reference (TEAC for both radicals. The kinetic curves for both radicals showed to follow the first order kinetics model and the decay rate constant (k obs was calculated. For all the samples, the two methods showed a good linear TEAC correlation, indicating that the average reactivity of the compounds present in the ethanolic extracts was similar. Sage and rosemary extracts showed the highest free radical scavenging capacities, while onion showed negligible activity and colorifico, one of the most consumed spices in Brazil, showed low ABTS•+ scavenging activity. Three distinct situations were found for the extracts concerning the DPPH• scavenging capacities: (1 extracts, like rosemary and laurel, that presented the same efficient concentrations (EC50 but differed in the TEAC values and velocities of action (k obs, (2 extracts, such as garlic and basil, that showed similar EC50 and TEAC values, but different k obs values and (3 extracts that reacted at the same velocities but completely differed in the free radical scavenging capacities, like black pepper, savory, nutmeg, rosemary and sage. Similar considerations could be done for the ABTS•+ results. For the first time the ABTS•+ scavenging activity for allspice, basil, cardamom, chives, colorifico, cumin, dill, laurel, marjoram, parsley and tarragon was reported.Extratos etanólicos de 23 ervas e condimentos desidratados comercializados no Brasil foram analisados quanto as suas propriedades antioxidantes utilizando os radicais 2,2'-difenil-β-picrilhidrazil (DPPH• e ácido 2,2'-azino-bis(3-etilbenzotiazolina-6-sulfônico (ABTS•+, Trolox foi usado como referência para ambos radicais

  3. Sesquiterpenoids with antialgal activity against the common red tide microalgae from marine macroalga Porphyra yezoensis.

    Science.gov (United States)

    Sun, Ying-Ying; Xing, Jing-Zeng; Zhang, Jian-Shuo; Zhou, Wen-Jing; Pu, Yin-Fang

    2018-03-01

    Previous studies showed that methanol extracts from Porphyra yezoensis significantly inhibited Karenia mikimitoi and Skeletonema costatum. Five sesquiterpenoids (1-5) were successfully isolated from this marine macroalga through a combination of silica gel column chromatography and repeated preparative thin-layer chromatography in this paper. Their structure was identified as gossonorol (1), 7,10-epoxy-ar-bisabol-11-ol (2), cyclonerodiol (3), cadinol, (4) and 4-cadinen-1-ol (5) on the basis of spectroscopic data. These sesquiterpenoids were isolated from Porphyra yezoensis for the first time, and cyclonerodiol (3) and cadinol (4) isolated from marine macroalgae for the first time. Further, a quantitative relationship between the inhibition of algal growth and the concentration of each antialgal sesquiterpenoid (gossonorol, 7,10-epoxy-ar-bisabol-11-ol and cyclonerodiol) was determined and important parameters, e.g., EC 50-96h for future practical HAB control are to be obtained. Results showed that three sesquiterpenoids (1-3) had selective antialgal activity against the growth of red tide microalgae (Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense, and Skeletonema costatum). More than two test red tide microalgae were significantly inhibited by these three sesquiterpenoids (1-3). Their antialgal activity against red tide microalgae has not been previously reported. Furthermore, EC 50-96h of gossonorol (1) and 7,10-epoxy-ar-bisabol-11-ol (2) for specific test red microalgae were not only significantly less than 10 μg/mL, but also were smaller than/or very close to those of potassium dichromate. Gossonorol (1) and 7,10-epoxy-ar-bisabol-11-ol (2) possessed good application potential than potassium dichromate as a characteristic antialgal agent against the specific harmful red tide microalgae (Heterosigma akashiwo, Phaeocystis globosa, and Prorocentrum donghaiense) (or Heterosigma akashiwo and Karenia

  4. Thresholds of arsenic toxicity to Eisenia fetida in field-collected agricultural soils exposed to copper mining activities in Chile.

    Science.gov (United States)

    Bustos, Víctor; Mondaca, Pedro; Verdejo, José; Sauvé, Sébastien; Gaete, Hernán; Celis-Diez, Juan L; Neaman, Alexander

    2015-12-01

    Several previous studies highlighted the importance of using field-collected soils-and not artificially-contaminated soils-for ecotoxicity tests. However, the use of field-collected soils presents several difficulties for interpretation of results, due to the presence of various contaminants and unavoidable differences in the physicochemical properties of the tested soils. The objective of this study was to estimate thresholds of metal toxicity in topsoils of 24 agricultural areas historically contaminated by mining activities in Chile. We performed standardized earthworm reproduction tests (OECD 222 and ISO 11268-2) with Eisenia fetida. Total soil concentrations of Cu, As, Zn, and Pb were in the ranges of 82-1295 mg kg(-1), 7-41 mg kg(-1), 86-345 mg kg(-1), and 25-97 mg kg(-1), respectively. In order to differentiate between the effects of different metals, we used regression analysis between soil metal concentrations and earthworm responses, as well as between metal concentrations in earthworm tissues and earthworm responses. Based on regression analysis, we concluded that As was a metal of prime concern for Eisenia fetida in soils affected by Cu mining activities, while Cu exhibited a secondary effect. In contrast, the effects of Zn and Pb were not significant. Soil electrical conductivity was another significant contributor to reproduction toxicity in the studied soils, forcing its integration in the interpretation of the results. By using soils with electrical conductivity ≤ 0.29 dS m(-1) (which corresponds to EC50 of salt toxicity to Eisenia fetida), it was possible to isolate the effect of soil salinity on earthworm reproduction. Despite the confounding effects of Cu, it was possible to determine EC10, EC25 and EC50 values for total soil As at 8 mg kg(-1), 14 mg kg(-1) and 22 mg kg(-1), respectively, for the response of the cocoon production. However, it was not possible to determine these threshold values for juvenile production. Likewise, we were able to

  5. The Fungicidal Activity of Tebuconazole Enantiomers against Fusarium graminearum and Its Selective Effect on DON Production under Different Conditions.

    Science.gov (United States)

    Diao, Xue; Han, Yiye; Liu, Chenglan

    2018-03-26

    Tebuconazole, which consists of a pair of enantiomers with different fungicidal activities, is one of the most common fungicides used in the control of Fusarium graminearum. In this study, the fungicidal activity of rac-tebuconazole and its enantiomers against F. graminearum was determined at 0.997, 0.975, and 0.950 a w and at 20, 25, and 30 °C on wheat-based media. Then, F. graminearum was treated with rac-tebuconazole and its enantiomers at the EC 10 , EC 50 , and EC 90 levels under different culture conditions, and DON production was measured. Finally, expression of the DON biosynthetic genes ( TRI5 and TRI6) was quantified by real-time RT-PCR after incubation with EC 50 doses of rac-tebuconazole and its enantiomers for 4, 8, and 14 days at 30 °C and a w 0.997. The results showed that the fungicidal activity of tebuconazole was strongly influenced by temperature, a w , and the combined factors. (-)-Tebuconazole is higher in fungicidal activity than (+)-tebuconazole and rac-tebuconazole with 24-99-fold and 1.8-6.7-fold, respectively. However, (-)-tebuconazole was generally more favorable for DON production than (+)-tebuconazole under the same conditions. Additionally, (-)-tebuconazole and rac-tebuconazole induced significantly increased expression of the DON biosynthetic genes ( TRI5 and TRI6) compared to the control by the 14th day of treatment. In this research, the combination condition of 30 °C and 0.997 a w is the most suitable for DON production by F. graminearum. The test strains of F. graminearum treated with the EC 10 dose of (-)-tebuconazole produced the greatest amounts of DON.

  6. Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice.

    Science.gov (United States)

    Ullrich, Nina D; Voets, Thomas; Prenen, Jean; Vennekens, Rudi; Talavera, Karel; Droogmans, Guy; Nilius, Bernd

    2005-03-01

    Non-selective cation (NSC) channels activated by intracellular Ca2+ ([Ca2+]i) play an important role in Ca2+ signaling and membrane excitability in many cell types. TRPM4 and TRPM5, two Ca2+-activated cation channels of the TRP superfamily, are potential molecular correlates of NSC channels. We compared the functional properties of mouse TRPM4 and TRPM5 heterologously expressed in HEK 293 cells. Dialyzing cells with different Ca2+ concentrations revealed a difference in Ca2+ sensitivity between TRPM4 and TRPM5, with EC50 values of 20.2+/-4.0 microM and 0.70+/-0.1 microM, respectively. Similarly, TRPM5 activated at lower Ca2+ concentration than TRPM4 when [Ca2+]i was raised by UV uncaging of the Ca2+-cage DMNP-EDTA. Current amplitudes of TRPM4 and TRPM5 were not correlated to the rate of changes in [Ca2+]i. The Ca2+ sensitivity of both channels was strongly reduced in inside-out patches, resulting in approximately 10-30 times higher EC50 values than under whole-cell conditions. Currents through TRPM4 and TRPM5 deactivated at negative and activated at positive potentials with similar kinetics. Both channels were equally sensitive to block by intracellular spermine. TRPM4 displayed a 10-fold higher affinity for block by flufenamic acid. Importantly, ATP4- blocked TRPM4 with high affinity (IC50 of 0.8+/-0.1 microM), whereas TRPM5 is insensitive to ATP4- at concentrations up to 1 mM.

  7. Anti-diabetic activity of fused PPARγ-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression.

    Science.gov (United States)

    Pirat, Celine; Dacquet, Catherine; Leclerc, Veronique; Hennuyer, Nathalie; Beucher-Gaudin, Monique; Zanirato, Ghislaine; Géant, Anne; Staels, Bart; Ktorza, Alain; Farce, Amaury; Caignard, Daniel-Henri; Berthelot, Pascal; Lebegue, Nicolas

    2017-09-08

    A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC 50  = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Biochemical Characterization and Antimicrobial and Antifungal Activity of Two Endemic Varieties of Garlic (Allium sativum L.) of the Campania Region, Southern Italy.

    Science.gov (United States)

    Fratianni, Florinda; Riccardi, Riccardo; Spigno, Patrizia; Ombra, Maria Neve; Cozzolino, Autilia; Tremonte, Patrizio; Coppola, Raffaele; Nazzaro, Filomena

    2016-07-01

    Extracts of the bulbs of the two endemic varieties "Rosato" and "Caposele" of Allium sativum of the Campania region, Southern Italy, were analyzed. The phenolic content, ascorbic acid, allicin content, and in vitro antimicrobial and antifungal activity were determined. Ultra performance liquid chromatography with diode array detector performed polyphenol profile. The polyphenolic extracts showed antioxidant activity (EC50) lower than 120 mg. The amount of ascorbic acid and allicin in the two extracts was similar. Polyphenol extract exhibited antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and (only by the extract of Rosato) against Bacillus cereus. The extract of Caposele was more effective in inhibiting the growth of Aspergillus versicolor and Penicillum citrinum. On the other hand, the extract of Rosato was effective against Penicillium expansum.

  9. Assessment of Cu applications in two contrasting soils-effects on soil microbial activity and the fungal community structure.

    Science.gov (United States)

    Keiblinger, Katharina M; Schneider, Martin; Gorfer, Markus; Paumann, Melanie; Deltedesco, Evi; Berger, Harald; Jöchlinger, Lisa; Mentler, Axel; Zechmeister-Boltenstern, Sophie; Soja, Gerhard; Zehetner, Franz

    2018-03-01

    Copper (Cu)-based fungicides have been used in viticulture to prevent downy mildew since the end of the 19th century, and are still used today to reduce fungal diseases. Consequently, Cu has built up in many vineyard soils, and it is still unclear how this affects soil functioning. The present study aimed to assess the short and medium-term effects of Cu contamination on the soil fungal community. Two contrasting agricultural soils, an acidic sandy loam and an alkaline silt loam, were used for an eco-toxicological greenhouse pot experiment. The soils were spiked with a Cu-based fungicide in seven concentrations (0-5000 mg Cu kg -1 soil) and alfalfa was grown in the pots for 3 months. Sampling was conducted at the beginning and at the end of the study period to test Cu toxicity effects on total microbial biomass, basal respiration and enzyme activities. Fungal abundance was analysed by ergosterol at both samplings, and for the second sampling, fungal community structure was evaluated via ITS amplicon sequences. Soil microbial biomass C as well as microbial respiration rate decreased with increasing Cu concentrations, with EC 50 ranging from 76 to 187 mg EDTA-extractable Cu kg -1 soil. Oxidative enzymes showed a trend of increasing activity at the first sampling, but a decline in peroxidase activity was observed for the second sampling. We found remarkable Cu-induced changes in fungal community abundance (EC 50 ranging from 9.2 to 94 mg EDTA-extractable Cu kg -1 soil) and composition, but not in diversity. A large number of diverse fungi were able to thrive under elevated Cu concentrations, though within the order of Hypocreales several species declined. A remarkable Cu-induced change in the community composition was found, which depended on the soil properties and, hence, on Cu availability.

  10. Hazelnut (Corylus avellana L. Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines

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    Tiziana Esposito

    2017-02-01

    Full Text Available Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE/g of extract. Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%–2.93%, w/w. The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH (EC50 = 31.7 μg/mL with respect to α-tocopherol EC50 = 10.1 μg/mL, and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 μg/mL, respectively. The expression of cleaved forms of caspase-3 and poly(ADP-ribose polymerase-1 (PARP-1 suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28 and human cervical cancer (HeLa cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin, and phenol derivatives (gallic acid, showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.

  11. Pereskia aculeata Muller (Cactaceae Leaves: Chemical Composition and Biological Activities

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    Lucèia Fàtima Souza

    2016-09-01

    Full Text Available The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE/g. The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.

  12. Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-regulated Kinase Inhibition.

    Science.gov (United States)

    Yap, Chee Voon; Subramaniam, Kavita S; Khor, Sik Wey; Chung, Ivy

    2017-01-01

    Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Annonacin, a natural pure compound extracted from the seeds of Annona muricata , is a potential alternative therapeutic agent to treat EC. To study the antitumor activity of annonacin and its mechanism of action in EC cells (ECCs). Viability of ECCs treated with annonacin for 72 h was determined using methyl thiazolyl tetrazolium assay. The induction of cell cycle arrest and apoptotic cell death was evaluated using propidium iodide and annexin V-PE/7-AAD assay, respectively. DNA strand breaks were visualized using transferase dUTP nick end labeling assay, and the effects of annonacin on survival signaling were determined using western blotting. Annonacin exhibited antiproliferative effects on EC cell lines (ECC-1 and HEC-1A) and primary cells (EC6-ept and EC14-ept) with EC 50 values ranging from 4.62 to 4.92 μg/ml. EC cells were shown arrested at G2/M phase after treated with 4 μg/ml of annonacin for 72 h. This led to a significant increase in apoptotic cell death (65.7%) in these cells when compared to vehicle-treated cells ( P cancer cells. Annonacin exerted antiproliferation effects on both endometrial cancer cell lines and primary cells via induction of apoptosis and inhibition of extracellular signal-regulated kinase. Our data represented that annonacin could be an alternative therapeutic treatment to combat endometrial cancer. Abbreviations Used: 7-AAD: 7-Amino-Actinomycin, ATP: Adenosine diphosphate, BSA: Bovine serum albumin, DNA: Deoxyribonucleic acid, EC: Endometrial cancer, ECC-1: Endometrial cancer cell-1, EC50: Half maximal effective concentration, Ept: Epithelial, FBS: Fetal bovine serum, HEC-1A: Human endometrial carcinoma-1A, MTT: Methyl thiazolyl tetrazolium, NaCl: Sodium chloride, NADH: Nicotinamide adenine dinucleotide, RPMI 1640: Roswell Park Memorial Institute Medium, SDS: Sodium dodecyl sulfate.

  13. 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine.

    Science.gov (United States)

    Barbosa-Lima, Giselle; Moraes, Adriana M; Araújo, Adriele da S; da Silva, Emerson T; de Freitas, Caroline S; Vieira, Yasmine R; Marttorelli, Andressa; Neto, José Cerbino; Bozza, Patrícia T; de Souza, Marcus V N; Souza, Thiago Moreno L

    2017-02-15

    Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine. We found that quinoline derivatives 3a and 4 were the most potent compounds within this series, both with mean EC 50 values of 0.8 μM, which represents a potency 5 times that of mefloquine. These results indicate that new 2,8-bis(trifluoromethyl)quinoline chemical structures may be promising for the development of novel anti-ZIKV drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Hoiamide a, a sodium channel activator of unusual architecture from a consortium of two papua new Guinea cyanobacteria.

    Science.gov (United States)

    Pereira, Alban; Cao, Zhengyu; Murray, Thomas F; Gerwick, William H

    2009-08-28

    Hoiamide A, a novel bioactive cyclic depsipeptide, was isolated from an environmental assemblage of the marine cyanobacteria Lyngbya majuscula and Phormidium gracile collected in Papua New Guinea. This stereochemically complex metabolite possesses a highly unusual structure, which likely derives from a mixed peptide-polyketide biogenetic origin, and includes a peptidic section featuring an acetate extended and S-adenosyl methionine modified isoleucine moiety, a triheterocyclic fragment bearing two alpha-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [(3)H]batrachotoxin binding to voltage-gated sodium channels (IC(50) = 92.8 nM), activated sodium influx (EC(50) = 2.31 microM) in mouse neocortical neurons, and exhibited modest cytotoxicity to cancer cells. Further investigation revealed that hoiamide A is a partial agonist of site 2 on the voltage-gated sodium channel.

  15. Anthelmintic properties of traditional African and Caribbean medicinal plants: identification of extracts with potent activity against Ascaris suum in vitro

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    Williams Andrew R.

    2016-01-01

    Full Text Available Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA with synthetic anthelmintic drugs such as albendazole, however continual re-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana and the Caribbean (US Virgin Islands for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very closely related to the human A. lumbricoides. A wide variety of activities were seen in the extracts, from negligible to potent. Extracts from Clausena anisata, Zanthoxylum zanthoxyloides and Punica granatum were identified as the most potent with EC50 values of 74, 97 and 164 μg/mL, respectively. Our results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA.

  16. Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida.

    Science.gov (United States)

    Wang, Kai; Qi, Suzhen; Mu, Xiyan; Chai, Tingting; Yang, Yang; Wang, Dandan; Li, Dongzhi; Che, Wunan; Wang, Chengju

    2015-10-01

    Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.

  17. Activity of ceftaroline against extracellular (broth) and intracellular (THP-1 monocytes) forms of methicillin-resistant Staphylococcus aureus: comparison with vancomycin, linezolid and daptomycin.

    Science.gov (United States)

    Mélard, Aurélie; Garcia, Laetitia G; Das, Debaditya; Rozenberg, Raoul; Tulkens, Paul M; Van Bambeke, Françoise; Lemaire, Sandrine

    2013-03-01

    Ceftaroline fosamil is approved for treatment of acute bacterial skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We examined the activity of its active metabolite (ceftaroline) against intracellular forms of S. aureus in comparison with vancomycin, daptomycin and linezolid. Two methicillin-susceptible S. aureus (MSSA) and 11 MRSA strains with ceftaroline MICs from 0.125 to 2 mg/L [two strains vancomycin- and one strain linezolid-resistant (EUCAST interpretative criteria); VISA and cfr+] were investigated. The activity was measured in broth and after phagocytosis by THP-1 monocytes in concentration-dependent experiments (24 h of incubation) to determine: (i) relative potencies (EC(50)) and static concentrations (C(s)) (mg/L and × MIC); and (ii) relative activities at human C(max) (E(C)(max)) and maximal relative efficacies (E(max)) (change in log(10) cfu compared with initial inoculum). Ceftaroline stability and cellular accumulation (at 24 h) were measured by mass spectrometry. Ceftaroline showed similar activities in broth and in monocytes compared with vancomycin, daptomycin and linezolid, with no impact of resistance mechanisms to vancomycin or linezolid. For all four antibiotics, intracellular E(C)(max) and E(max) were considerably lower than in broth (∼0.5 log(10) versus 4-5 log(10) cfu decrease), but the EC(50) and C(s) showed comparatively little change (all values between ∼0.3 and ∼6× MIC). The mean cellular to extracellular ceftaroline concentration ratios (20 mg/L; 24 h) were 0.66 ± 0.05 and 0.90 ± 0.36 in uninfected and infected cells, respectively. In vitro, ceftaroline controls the growth of intracellular MRSA to an extent similar to that of vancomycin, linezolid and daptomycin for strains with a ceftaroline MIC ≤ 2 mg/L.

  18. Anti-trypanosomal activity of 1,2,3,4,6-penta-O-galloyl-β -D-glucose isolated from Plectranthus barbatus Andrews (Lamiaceae

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    Roberta T. dos Santos

    2012-01-01

    Full Text Available MeOH extract from the leaves of Plectranthus barbatus Andrews (Lamiaceae, showed in vitro anti-trypanosomal activity. The bioassay-guided fractionation resulted in the isolation of a gallic acid derivative, identified as 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG, after thorough NMR and MS spectral analysis. Finally, this compound was tested against trypomastigote forms of T. cruzi and displayed an EC50 value of 67 µM, at least 6.6-fold more effective than the standard drug benznidazole. This is the first occurrence of PGG in the Plectranthus genus and the first anti-parasitic activity described for PGG in the literature.

  19. Anti-trypanosomal activity of 1,2,3,4,6-penta-O-galloyl-? -D-glucose isolated from Plectranthus barbatus Andrews (Lamiaceae)

    International Nuclear Information System (INIS)

    Santos, Roberta T. dos; Hiramoto, Liliane L.; Lago, Joao Henrique G.; Sartorelli, Patricia

    2012-01-01

    MeOH extract from the leaves of Plectranthus barbatus Andrews (Lamiaceae), showed in vitro anti-trypanosomal activity. The bioassay-guided fractionation resulted in the isolation of a gallic acid derivative, identified as 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), after thorough NMR and MS spectral analysis. Finally, this compound was tested against trypomastigote forms of T. cruzi and displayed an EC 50 value of 67 μM, at least 6.6-fold more effective than the standard drug benznidazole. This is the first occurrence of PGG in the Plectranthus genus and the first anti-parasitic activity described for PGG in the literature (author)

  20. Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication

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    Mélanie Bourjot

    2014-03-01

    Full Text Available Trigocherrierin A (1 and trigocherriolide E (2, two new daphnane diterpenoid orthoesters (DDOs, and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7.

  1. In vitro anti-reovirus activity of kuraridin isolated from Sophora flavescens against viral replication and hemagglutination

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    Hyung-Jun Kwon

    2015-08-01

    Full Text Available In this study, we evaluated the anti-reovirus activity of kuraridin isolated from the roots of Sophora flavescens. In particular, we focused on whether this property is attributable to direct inhibition of reovirus attachment and/or inhibition of viral replication with the aid of time-of-addition (pre-treatment, simultaneous treatment, and post-treatment experiments. No significant antiviral activity of kuraridin was detected in the pre-treatment assay. In the simultaneous assay, the 50% effective inhibitory concentrations (EC50 of kuraridin were 15.3–176.9 μM against human type 1–3 reoviruses (HRV1–3 and Korean porcine reovirus (PRV. Kuraridin completely blocked binding of viral sigma 1 protein to sialic acids at concentrations lower than 82.5 μM in the hemagglutination inhibition assay. Moreover, kuraridin inhibited HRV1–3 and PRV viral replication with EC50 values of 14.0–62.0 μM. Quantitative real-time PCR analysis disclosed strong suppression of reovirus RNA synthesis at the late stage (18 h of virus replication by kuraridin. The viral yields of kuraridin-treated cells were significantly reduced at 24 h post-infection, compared with DMSO-treated cells. Our results collectively suggest that kuraridin inhibits virus adsorption and replication by inhibiting hemagglutination, viral RNA and protein synthesis and virus shedding, supporting its utility as a viable candidate antiviral drug against reoviruses.

  2. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates.

    Science.gov (United States)

    Visseaux, Benoit; Charpentier, Charlotte; Collin, Gilles; Bertine, Mélanie; Peytavin, Gilles; Damond, Florence; Matheron, Sophie; Lefebvre, Eric; Brun-Vézinet, Françoise; Descamps, Diane

    2015-01-01

    Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 antagonist that has completed Phase 2b development in HIV-1 infection. Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3) cell lines. Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI) of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively). The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively. In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted.

  3. Design, Synthesis and Fungicidal Activities of Some Novel Pyrazole Derivatives

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    Xue-Ru Liu

    2014-09-01

    Full Text Available In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS, and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank Donk, Fusarium oxysporum (S-chl f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27–32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.

  4. Chemical composition and antioxidant activity of two strawberry cultivars

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    Đilas Sonja M.

    2011-01-01

    Full Text Available The macro- and micro-chemical composition, as well as antioxidant activity of two strawberry cultivars, Marmolada and Clery, were studied. Results showed a noticeable difference in the sugar, protein and pectin contents. Clery had 6.92% and Marmolada 4.93% of total sugar. Also, protein and pectin contents were higher in the Clery cultivar. No significant difference was observed in acidity, as well as in ash and cellulose content. Marmolada had a higher content of total phenolics and flavonoids (228.04 mg GAE /100 g FW and 136.01 mg RE/100 g FW, respectively . The anthocyanins content in Marmolada (32.0 mg CGE/100 g FW was slightly lower than in Clery (36.0 mg CGE/100 g FW. The antioxidant activity was evaluated spectrophotometrically, using 2,2-diphenyl- 1-picrylhydrazyl (DPPH radical scavenging activity assay. The DPPH free radical scavenging activity, expressed as EC50 value, of Marmolada (0.77 mg/ml was higher than of Clery (0.83 mg/ml. There was a significant positive correlation (R2>0.90 between the concentration of phenolics/flavonoids/anthocyanins and DPPH radical scavenging activity of both strawberry cultivars. These results also showed that the antioxidant value of 100 g FW Marmolada and Clery is equivalent to 237.91 mg and 219.01 mg of vitamin C, respectively.

  5. Antifungal activity, main active components and mechanism of Curcuma longa extract against Fusarium graminearum

    Science.gov (United States)

    Zhang, Fusheng; Chen, Qin; Chen, Cheng; Yu, Xiaorui; Liu, Qingya; Bao, Jinku

    2018-01-01

    Curcuma longa possesses powerful antifungal activity, as demonstrated in many studies. In this study, the antifungal spectrum of Curcuma longa alcohol extract was determined, and the resulting EC50 values (mg/mL) of its extract on eleven fungi, including Fusarium graminearum, Fusarium chlamydosporum, Alternaria alternate, Fusarium tricinctum, Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium culmorum, Rhizopus oryzae, Cladosporium cladosporioides, Fusarium oxysporum and Colletotrichum higginsianum, were 0.1088, 0.1742, 0.1888, 0.2547, 0.3135, 0.3825, 0.4229, 1.2086, 4.5176, 3.8833 and 5.0183, respectively. Among them, F. graminearum was selected to determine the inhibitory effects of the compounds (including curdione, isocurcumenol, curcumenol, curzerene, β-elemene, curcumin, germacrone and curcumol) derived from Curcuma longa. In addition, the antifungal activities of curdione, curcumenol, curzerene, curcumol and isocurcumenol and the synergies of the complexes of curdione and seven other chemicals were investigated. Differential proteomics of F. graminearum was also compared, and at least 2021 reproducible protein spots were identified. Among these spots, 46 were classified as differentially expressed proteins, and these proteins are involved in energy metabolism, tRNA synthesis and glucose metabolism. Furthermore, several fungal physiological differences were also analysed. The antifungal effect included fungal cell membrane disruption and inhibition of ergosterol synthesis, respiration, succinate dehydrogenase (SDH) and NADH oxidase. PMID:29543859

  6. In vitro Serotonergic Activity of Black Cohosh and Identification of Nω-Methylserotonin as a Potential Active Constituent

    Science.gov (United States)

    POWELL, SHARLA L.; GÖDECKE, TANJA; NIKOLIC, DEJAN; CHEN, SHAO-NONG; AHN, SOYOUN; DIETZ, BIRGIT; FARNSWORTH, NORMAN R.; VAN BREEMEN, RICHARD B.; LANKIN, DAVID; PAULI, GUIDO F.; BOLTON, JUDY L.

    2013-01-01

    Cimicifuga racemosa(L.) Nutt. (syn. Actaea racemosa L., black cohosh) is used to relieve menopausal hot flashes, although clinical studies have provided conflicting data, and the active constituent(s) and mechanism(s) of action remain unknown. Since serotonergic receptors and transporters are involved with thermoregulation, black cohosh and its phytoconstituents were evaluated for serotonergic activity using 5-HT7 receptor binding, cAMP induction, and serotonin selective reuptake inhibitor (SSRI) assays. Crude extracts displayed 5-HT7 receptor binding activity and induced cAMP production. Fractionation of the methanol extract lead to isolation of phenolic acids and identification of Nω-methylserotonin by LC/MS-MS. Cimicifuga triterpenoids and phenolic acids bound weakly to the 5-HT7 receptor with no cAMP or SSRI activity. In contrast, Nω-methylserotonin showed 5-HT7 receptor binding (IC50 23 pM), induced cAMP (EC50 22 nM), and blocked serotonin reuptake (IC50 490 nM). These data suggest Nω-methylserotonin may be responsible for the serotonergic activity of black cohosh. PMID:19049296

  7. Dual role of novel ingenol derivatives from Euphorbia tirucalli in HIV replication: inhibition of de novo infection and activation of viral LTR.

    Directory of Open Access Journals (Sweden)

    Celina M Abreu

    Full Text Available HIV infection is not cleared by antiretroviral drugs due to the presence of latently infected cells that are not eliminated with current therapies and persist in the blood and organs of infected patients. New compounds to activate these latent reservoirs have been evaluated so that, along with HAART, they can be used to activate latent virus and eliminate the latently infected cells resulting in eradication of viral infection. Here we describe three novel diterpenes isolated from the sap of Euphorbia tirucalli, a tropical shrub. These molecules, identified as ingenols, were modified at carbon 3 and termed ingenol synthetic derivatives (ISD. They activated the HIV-LTR in reporter cell lines and human PBMCs with latent virus in concentrations as low as 10 nM. ISDs were also able to inhibit the replication of HIV-1 subtype B and C in MT-4 cells and human PBMCs at concentrations of EC50 0.02 and 0.09 µM respectively, which are comparable to the EC50 of some antiretroviral currently used in AIDS treatment. Control of viral replication may be caused by downregulation of surface CD4, CCR5 and CXCR4 observed after ISD treatment in vitro. These compounds appear to be less cytotoxic than other diterpenes such as PMA and prostratin, with effective dose versus toxic dose TI>400. Although the mechanisms of action of the three ISDs are primarily attributed to the PKC pathway, downregulation of surface receptors and stimulation of the viral LTR might be differentially modulated by different PKC isoforms.

  8. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome

    Directory of Open Access Journals (Sweden)

    Nadja S. Vila-Nova

    2012-11-01

    Full Text Available In recent years, the Brazilian Health Ministry and the World Health Organization have supported research into new technologies that may contribute to the surveillance, new treatments, and control of visceral leishmaniasis within the country. In light of this, the aim of this study was to isolate compounds from plants of the Caatinga biome, and to investigate their toxicity against promastigote and amastigote forms of Leishmania infantum chagasi, the main responsible parasite for South American visceral leishmaniasis, and evaluate their ability to inhibit acetylcholinesterase enzyme (AChE. A screen assay using luciferase-expressing promastigote form and an in situ ELISA assay were used to measure the viability of promastigote and amastigote forms, respectively, after exposure to these substances. The MTT colorimetric assay was performed to determine the toxicity of these compounds in murine monocytic RAW 264.7 cell line. All compounds were tested in vitro for their anti-cholinesterase properties. A coumarin, scoparone, was isolated from Platymiscium floribundum stems, and the flavonoids rutin and quercetin were isolated from Dimorphandra gardneriana beans. These compounds were purified using silica gel column chromatography, eluted with organic solvents in mixtures of increasing polarity, and identified by spectral analysis. In the leishmanicidal assays, the compounds showed dose-dependent efficacy against the extracellular promastigote forms, with an EC50 for scoporone of 21.4µg/mL, quercetin and rutin 26 and 30.3µg/mL, respectively. The flavonoids presented comparable results to the positive control drug, amphotericin B, against the amastigote forms with EC50 for quercetin and rutin of 10.6 and 43.3µg/mL, respectively. All compounds inhibited AChE with inhibition zones varying from 0.8 to 0.6, indicating a possible mechanism of action for leishmacicidal activity.

  9. Antibacterial, antioxidant, and anticholinesterase activities of plant seed extracts from Brazilian semiarid region.

    Science.gov (United States)

    Farias, Davi Felipe; Souza, Terezinha Maria; Viana, Martônio Ponte; Soares, Bruno Marques; Cunha, Arcelina Pacheco; Vasconcelos, Ilka Maria; Ricardo, Nágila Maria Pontes Silva; Ferreira, Paulo Michel Pinheiro; Melo, Vânia Maria Maciel; Carvalho, Ana Fontenele Urano

    2013-01-01

    The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (-) organism Salmonella choleraesuis and the Gram (+) organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μ g/mL (T. gardneriana) to 487.51 μ g/mL (Licania rigida). For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL). Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay.

  10. Antibacterial, Antioxidant, and Anticholinesterase Activities of Plant Seed Extracts from Brazilian Semiarid Region

    Directory of Open Access Journals (Sweden)

    Davi Felipe Farias

    2013-01-01

    Full Text Available The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (− organism Salmonella choleraesuis and the Gram (+ organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μg/mL (T. gardneriana to 487.51 μg/mL (Licania rigida. For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL. Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay.

  11. Antioxidant activity, the content of total phenols and flavonoids in the ethanol extracts of Mentha longifolia (L. Hudson dried by the use of different techniques

    Directory of Open Access Journals (Sweden)

    Stanisavljević Dragana M.

    2012-01-01

    Full Text Available In this study, we have examined the yield of extracted substances obtained by means of extraction using 70 % ethanol (v/v, the content of total phenols and flavonoids, as well as the antioxidant activity of the extracts obtained from the samples of the herbs dried by means of different techniques. Wild mint Mentha longifolia (L. Hudson was dried naturally in a laboratory oven at a temperature of 45 °C and in an absorptive low temperature condensation oven at 35°C. The highest yield of extracts was obtained from the naturally dried herbs and the lowest from the herbs dried in the low temperature condensation drying oven. The content of total phenols and flavonoids was determined by spectrophotometric methods with an FC reagent and by the complexation reaction with aluminium-chloride, respectively. The extract of the naturally dried herbs had the highest overall content of phenols (113.8±2.0 mg of gallic acid/g of the dry extract and flavonoids (106.7±0.3 mg of rutin/g of the dry extract. The highest antioxidant activity determined by the FRAP and DPPH assay was determined in the extracts obtained from naturally dried herbs (2.76±0.15 mmol Fe2+/mg of the dry extract and EC50=0.022±0.001 mg/ml, while the lowest was obtained from the extracts of herbs dried in the laboratory oven (1.13±0.11 mmol Fe2+/mg of the dry extract and EC50=0.033±0.001 mg/ml. The HPLC-DAD analysis result show that the greatest content of phenolic compounds show extract obtained from naturally dried plant material. The dominant phenolic component in the all extracts is Kaempferol 3-O-glucoside. The content of all phenolic compound strongly depend on the drying conditions.

  12. Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone.

    Science.gov (United States)

    McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V; Power, John D; Dowling, Geraldine; Twamley, Brendan; O'Brien, John; Talbot, Brian; Walther, Donna; Partilla, John S; Baumann, Michael H; Brandt, Simon D

    2017-03-01

    3-Methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone) appeared in 2015 and was advertised by UK Internet retailers as a non-controlled mephedrone derivative (2-(methylamino)-1-(4-methylphenyl)propan-1-one), which was of particular interest to countries who operate generic drugs legislation. This study describes the synthesis and analytical characterization of mexedrone and the differentiation from its isomer, N-methoxymephedrone, which was predicted to be a suitable candidate before the identity of mexedrone was revealed. A full analytical characterization is described using various chromatographic, spectroscopic and mass spectrometric platforms and X-ray crystal structure analysis. The analytical data obtained for a vendor sample were consistent with the synthesized mexedrone reference standard and analytical differentiation between the mexedrone and N-methoxymephedrone positional isomers was achieved. Furthermore, α-chloromethylmephedrone was identified as a by-product during mexedrone synthesis. All three substances were also studied for their uptake and releasing properties at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) using in vitro monoamine transporter assays in rat brain synaptosomes and compared to mephedrone. Mexedrone was a weak non-selective uptake blocker with IC 50 values in the low μM range. It was also devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC 50  = 2.5 μM). The isomer N-methoxymephedrone was found to be a weak uptake blocker at DAT, NET and SERT, as well as a fully efficacious substrate-type releasing agent across all three transporters with EC 50 values in the low micromolar range. The synthesis by-product α-chloromethylmephedrone was inactive in all assays. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Effect of chromium oxide (III) nanoparticles on the production of reactive oxygen species and photosystem II activity in the green alga Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Costa, Cristina Henning da; Perreault, François; Oukarroum, Abdallah; Melegari, Sílvia Pedroso; Popovic, Radovan; Matias, William Gerson

    2016-01-01

    With the growth of nanotechnology and widespread use of nanomaterials, there is an increasing risk of environmental contamination by nanomaterials. However, the potential implications of such environmental contamination are hard to evaluate since the toxicity of nanomaterials if often not well characterized. The objective of this study was to evaluate the toxicity of a chromium-based nanoparticle, Cr 2 O 3 -NP, used in a wide diversity of industrial processes and commercial products, on the unicellular green alga Chlamydomonas reinhardtii. The deleterious impacts of Cr 2 O 3 -NP were characterized using cell density measurements, production of reactive oxygen species (ROS), esterase enzymes activity, and photosystem II electron transport as indicators of toxicity. Cr 2 O 3 -NP exposure inhibited culture growth and significantly lowered cellular Chlorophyll a content. From cell density measurements, EC50 values of 2.05 ± 0.20 and 1.35 ± 0.06 g L −1 Cr 2 O 3 -NP were obtained after 24 and 72 h of exposure, respectively. In addition, ROS levels were increased to 160.24 ± 2.47% and 59.91 ± 0.15% of the control value after 24 and 72 h of exposition to 10 g L −1 Cr 2 O 3 -NP. At 24 h of exposure, the esterase activity increased to 160.24% of control value, revealing a modification of the short-term metabolic response of algae to Cr 2 O 3 -NP exposure. In conclusion, the metabolism of C. reinhardtii was the most sensitive to Cr 2 O 3 -NP after 24 h of treatment. - Highlights: • Cr 2 O 3 nanoparticles are unstable and form large aggregates in the medium. • EC50 for growth inhibition of C. reinhardtii is 1.35 g L −1 at 72 h. • Cr 2 O 3 nanoparticles increase ROS levels at 10 g L −1 . • Cr 2 O 3 nanoparticles affect photosynthetic electron transport.

  14. Biological activities of undescribed North American lichen species.

    Science.gov (United States)

    Yeash, Erik A; Letwin, Lyndon; Malek, Lada; Suntres, Zacharias; Knudsen, Kerry; Christopher, Lew P

    2017-11-01

    Lichens provide a large array of compounds with the potential for pharmaceutical development. In the present study, extracts from three previously undescribed North American lichen species were examined for antioxidant, antibacterial and anticancer activities. The results from this study demonstrated the following: (i) Acarospora socialis ethanol extract exhibited significant DPPH antioxidant scavenging activities, which were concentration dependent; (ii) acetone and ethyl acetate extracts of Xanthoparmelia mexicana inhibited Gram-positive bacteria but had no effect on Gram-negative bacteria; X. mexicana acetone extract yielded a minimum inhibitory concentration (MIC) of 20.9 µg mL -1 against Staphylococcus aureus, and 41.9 µg mL -1 against Enterococcus faecalis; (iii) acetone extract of Lobothallia alphoplaca inhibited growth of cultured breast cancer MCF-7 cells with an effective concentration (EC 50 ) of 87 µg mL -1 ; the MCF-7 cell cycle appears arrested in the G2 phase, whereas the DNA synthesis cell cycle (S) may be inhibited. New lichen species that possess strong biological activities have been identified. These lichens comprise secondary metabolites that possess antioxidant, antibacterial and anticancer properties. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  15. Spermicidal activity of Indian seaweeds: an in vitro study.

    Science.gov (United States)

    Prakash, S; Ravikumar, S; Reddy, K V R; Kannapiran, E

    2014-05-01

    Contraceptive properties of seaweeds are still stands as lacuna; in this context, the screening of in vitro male contraceptive properties of crude ethanolic extract of Indian seaweeds against normal human sperm is carried out. In total, twelve seaweeds were screened for in vitro spermicidal activity. Among these twelve seaweeds, Halimeda gracilis showed 100% inhibition of human spermatozoa at 10 mg ml(-1) concentration in 20 s and its EC50 value was 2.05 mg ml(-1) in 20 s. Further, dose- and time-dependent spermicidal assay revealed that the sperm was completely immobilised for 20 s. Plasma membrane of sperm was damaged due to the exposure of H. gracilis extract. MTT assay with H. gracilis extract showed 88.5% of cytotoxic incidence. H. gracilis extract tested for cytotoxicity against Artemia salina recorded LC50 value of 34.8 μg ml(-1) . Phytochemical analysis of H. gracilis extract evidenced the presence of alkaloids, flavonoids, proteins and sugars. Results of this study clearly inferred that the synergistic effect of active principles reside within the H. gracilis extract had shown better contraceptive activity. © 2013 Blackwell Verlag GmbH.

  16. Activity of moxifloxacin against intracellular community-acquired methicillin-resistant Staphylococcus aureus: comparison with clindamycin, linezolid and co-trimoxazole and attempt at defining an intracellular susceptibility breakpoint.

    Science.gov (United States)

    Lemaire, Sandrine; Kosowska-Shick, Klaudia; Appelbaum, Peter C; Glupczynski, Y; Van Bambeke, Françoise; Tulkens, Paul M

    2011-03-01

    Co-trimoxazole, clindamycin and linezolid are used to treat community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but little is known about intracellular activity. Moxifloxacin is active against intracellular methicillin-susceptible S. aureus (MSSA), but CA-MRSA has not been studied. We used 12 clinical CA-MRSA, 1 MSSA overexpressing norA and 2 hospital-acquired MRSA (moxifloxacin MICs: 0.03 to 4 mg/L). Activity was assessed in broth and after phagocytosis by THP-1 macrophages or keratinocytes {concentration-dependent experiments [24 h of incubation] to determine relative potencies [EC(50)], static concentrations [C(s)] and maximal relative efficacies [E(max) (change in log(10) cfu compared with initial inoculum)] and time-dependent experiments [0-72 h] at human C(max)}. Concentration-dependent experiments: in broth, EC(50) and C(s) were correlated with the MIC for all antibiotics, but moxifloxacin achieved significantly (P linezolid were static, and co-trimoxazole was unable to suppress the intracellular growth of CA-MRSA. At human C(max) in broth, moxifloxacin killed more rapidly and more extensively (≥5 log(10) cfu decrease at 10 h) than clindamycin (4 log(10) cfu at 48 h) or co-trimoxazole and linezolid (1-2 log(10) cfu at 72 h). Moxifloxacin is active against both extracellular and intracellular CA-MRSA if the MIC is low, and is more effective than clindamycin, co-trimoxazole and linezolid.

  17. Tonoplast anion channel activity modulation by pH in Chara corallina.

    Science.gov (United States)

    Berecki, G; Eijken, M; Van Iren, F; Van Duijn, B

    2001-11-15

    The patch-clamp technique was used to investigate regulation of anion channel activity in the tonoplast of Chara corallina in response to changing proton and calcium concentrations on both sides of the membrane. These channels are known to be Ca2+-dependent, with conductances in the range of 37 to 48 pS at pH 7.4. By using low pH at the vacuolar side (either pH(vac) 5.3 or 6.0) and a cytosolic pH (pH(cyt)) varying in a range of 4.3 to 9.0, anion channel activity and single-channel conductance could be reversibly modulated. In addition, Ca2+-sensitivity of the channels was markedly influenced by pH changes. At pH(cyt) values of 7.2 and 7.4 the half-maximal concentration (EC50) for calcium activation was 100-200 microm, whereas an EC(50) of about 5 microm was found at a pH(cyt) of 6.0. This suggests an improved binding of Ca2+ ions to the channel protein at more acidic cytoplasm. At low pH(cyt), anion channel activity and mean open times were voltage-dependent. At pipette potentials (V(p)) of +100 mV, channel activity was approximately 15-fold higher than activity at negative pipette potentials and the mean open time of the channel increased. In contrast, at pH(cyt) 7.2, anion channel activity and the opening behavior seemed to be independent of the applied V(p). The kinetics of the channel could be further controlled by the Ca2+ concentration at the cytosolic membrane side: the mean open time significantly increased in the presence of a high cytosolic Ca2+ concentration. These results show that tonoplast anion channels are maintained in a highly active state in a narrow pH range, below the resting pH(cyt). A putative physiological role of the pH-dependent modulation of these anion channels is discussed.

  18. Blandford's argument: The strongest continuous gravitational wave signal

    International Nuclear Information System (INIS)

    Knispel, Benjamin; Allen, Bruce

    2008-01-01

    For a uniform population of neutron stars whose spin-down is dominated by the emission of gravitational radiation, an old argument of Blandford states that the expected gravitational-wave amplitude of the nearest source is independent of the deformation and rotation frequency of the objects. Recent work has improved and extended this argument to set upper limits on the expected amplitude from neutron stars that also emit electromagnetic radiation. We restate these arguments in a more general framework, and simulate the evolution of such a population of stars in the gravitational potential of our galaxy. The simulations allow us to test the assumptions of Blandford's argument on a realistic model of our galaxy. We show that the two key assumptions of the argument (two dimensionality of the spatial distribution and a steady-state frequency distribution) are in general not fulfilled. The effective scaling dimension D of the spatial distribution of neutron stars is significantly larger than two, and for frequencies detectable by terrestrial instruments the frequency distribution is not in a steady state unless the ellipticity is unrealistically large. Thus, in the cases of most interest, the maximum expected gravitational-wave amplitude does have a strong dependence on the deformation and rotation frequency of the population. The results strengthen the previous upper limits on the expected gravitational-wave amplitude from neutron stars by a factor of 6 for realistic values of ellipticity.

  19. The Philippine tobacco industry: "the strongest tobacco lobby in Asia"

    OpenAIRE

    Alechnowicz, K; Chapman, S

    2004-01-01

    Objective: To highlight revelations from internal tobacco industry documents about the conduct of the industry in the Philippines since the 1960s. Areas explored include political corruption, health, employment of consultants, resisting pack labelling, and marketing and advertising.

  20. The origin of the strongest magnetic fields in dwarfs

    Indian Academy of Sciences (India)

    Sky Survey (SDSS) but none of these shows sufficient evidence for Zeeman splitting of hydrogen lines for a magnetic field in ... to be done and hence the electrons exert a pressure. Chandrasekhar [2] ..... Three methods have been used to estimate masses for suitable magnetic white dwarfs. First, if the field strength is of ...

  1. Highly Charged Protein Ions: The Strongest Organic Acids to Date.

    Science.gov (United States)

    Zenaidee, Muhammad A; Leeming, Michael G; Zhang, Fangtong; Funston, Toby T; Donald, William A

    2017-07-10

    The basicity of highly protonated cytochrome c (cyt c) and myoglobin (myo) ions were investigated using tandem mass spectrometry, ion-molecule reactions (IMRs), and theoretical calculations as a function of charge state. Surprisingly, highly charged protein ions (HCPI) can readily protonate non-polar molecules and inert gases, including Ar, O 2 , and N 2 in thermal IMRs. The most HCPIs that can be observed are over 130 kJ mol -1 less basic than the least basic neutral organic molecules known (tetrafluoromethane and methane). Based on theoretical calculations, it is predicted that protonated cyt c and myo ions should spontaneously lose a proton to vacuum for charge states in which every third residue is protonated. In this study, HCPIs are formed where every fourth residue on average is protonated. These results indicate that protein ions in higher charge states can be formed using a low-pressure ion source to reduce proton-transfer reactions between protein ions and gases from the atmosphere. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The origin of the strongest magnetic fields in dwarfs

    Indian Academy of Sciences (India)

    Thus, we deduce that the origin of such high magnetic fields must be intimately tied to the formation of cataclysmic variables (CVs). The formation of a CV must involve orbital shrinkage from giant star to main-sequence star dimensions. It is believed that this shrinkage occurs as the low-mass companion and the white dwarf ...

  3. Hexachlorophene is a potent KCNQ1/KCNE1 potassium channel activator which rescues LQTs mutants.

    Science.gov (United States)

    Zheng, Yueming; Zhu, Xuejing; Zhou, Pingzheng; Lan, Xi; Xu, Haiyan; Li, Min; Gao, Zhaobing

    2012-01-01

    The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC(50) of 4.61 ± 1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics.

  4. Hexachlorophene is a potent KCNQ1/KCNE1 potassium channel activator which rescues LQTs mutants.

    Directory of Open Access Journals (Sweden)

    Yueming Zheng

    Full Text Available The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs. Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP, the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC(50 of 4.61 ± 1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2 binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics.

  5. Hexachlorophene Is a Potent KCNQ1/KCNE1 Potassium Channel Activator Which Rescues LQTs Mutants

    Science.gov (United States)

    Zheng, Yueming; Zhu, Xuejing; Zhou, Pingzheng; Lan, Xi; Xu, Haiyan; Li, Min; Gao, Zhaobing

    2012-01-01

    The voltage-gated KCNQ1 potassium channel is expressed in cardiac tissues, and coassembly of KCNQ1 with an auxiliary KCNE1 subunit mediates a slowly activating current that accelerates the repolarization of action potential in cardiomyocytes. Mutations of KCNQ1 genes that result in reduction or loss of channel activity cause prolongation of repolarization during action potential, thereby causing long QT syndrome (LQTs). Small molecule activators of KCNQ1/KCNE1 are useful both for understanding the mechanism of the complex activity and for developing therapeutics for LQTs. In this study we report that hexachlorophene (HCP), the active component of the topical anti-infective prescription drug pHisoHex, is a KCNQ1/KCNE1 activator. HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC50 of 4.61±1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity. Our results indicate HCP is a novel KCNQ1/KCNE1 activator and may be a useful tool compound for the development of LQTs therapeutics. PMID:23251633

  6. Chemical composition, insecticidal, and antifungal activities of fruit essential oils of three colombian Zanthoxylum species Composición química, actividades insecticida y antifúngica de aceites esenciales de frutos de tres especies Zanthoxylum de Colombia

    Directory of Open Access Journals (Sweden)

    Juliet A Prieto

    2011-03-01

    Full Text Available This study determined the chemical composition of essential oils isolated from Zanthoxylum monophyllum (Lam. P. Wilson, Z. rhoifolium Lam., and Z. fagara (L. Sarg. fruits by steam distillation, as well as testing antifungal and insecticidal activities of essential oils as potential pesticides. Gas chromatography-mass spectrometry (GC/MS analysis identified 57 compounds. The main constituents in Z. rhoifolium oil were β-Myrcene (59.03%, β-phellandrene (21.47%, and germacrene D (9.28% , the major constituents of Z. monophyllum oil were sabinene (25.71%, 1,8-cineole (9.19%, and cis-4-thujanol (9.19%, whereas fruit oil of Z. fagara mainly contained germacrene D-4-ol (21.1%, elemol (8.35%, and α-cadinol (8.22%. Zanthoxylum fagara showed the highest activity on Colletotrichum acutatum Simmonds (EC50 153.9 μL L-1 air, and Z. monophyllum was the most active against Fusarium oxysporum Schlechtend: Fr. f. sp. lycopersici (EC50 140.1 μL L-1 air. Zanthoxylum monophyllum essential oil showed significant fumigant activity against Sitophilus oryzae (L.. This study demonstrated that Zanthoxylum essential oils exhibit important fungicidal activity on F. oxysporum and C. acutatum, which could become an alternative to synthetic fungicides to control plant fungal diseases, and Z. monophyllum oil is a potential fumigant against S. oryzae.En este estudio se determinó la composición química de los aceites esenciales de frutos de Zanthoxylum monophyllum (Lam. P. Wilson, Z. rhoifolium Lam. y Z. fagara (L. Sarg. obtenidos mediante destilación por arrastre con vapor y se evaluó la actividad antifúngica e insecticida de los aceites esenciales para estimar su uso como posibles plaguicidas. El análisis por cromatografía de gases-espectrometría de masas (CG/EM permitió la identificación de 57 compuestos. β-Mirceno (59,03%, β-felandreno (21,47% y germacreno D (9,28% fueron los componentes principales del aceite de Z. rhoifolium; los principales componentes

  7. A Modified P1 Moiety Enhances In Vitro Antiviral Activity against Various Multidrug-Resistant HIV-1 Variants and In Vitro Central Nervous System Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413.

    Science.gov (United States)

    Amano, Masayuki; Salcedo-Gómez, Pedro Miguel; Zhao, Rui; Yedidi, Ravikiran S; Das, Debananda; Bulut, Haydar; Delino, Nicole S; Sheri, Venkata Reddy; Ghosh, Arun K; Mitsuya, Hiroaki

    2016-12-01

    We report here that GRL-10413, a novel nonpeptidic HIV-1 protease inhibitor (PI) containing a modified P1 moiety and a hydroxyethylamine sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC 50 ] of 0.00035 to 0.0018 μM), with minimal cytotoxicity (50% cytotoxic concentration [CC 50 ] = 35.7 μM). GRL-10413 blocked the infectivity and replication of HIV-1 NL4-3 variants selected by use of atazanavir, lopinavir, or amprenavir (APV) at concentrations of up to 5 μM (EC 50 = 0.0021 to 0.0023 μM). GRL-10413 also maintained its strong antiviral activity against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to various antiviral regimens after long-term antiretroviral therapy. The development of resistance against GRL-10413 was significantly delayed compared to that against APV. In addition, GRL-10413 showed favorable central nervous system (CNS) penetration properties as assessed with an in vitro blood-brain barrier (BBB) reconstruction system. Analysis of the crystal structure of HIV-1 protease in complex with GRL-10413 demonstrated that the modified P1 moiety of GRL-10413 has a greater hydrophobic surface area and makes greater van der Waals contacts with active site amino acids of protease than in the case of darunavir. Moreover, the chlorine substituent in the P1 moiety interacts with protease in two distinct configurations. The present data demonstrate that GRL-10413 has desirable features for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants, with favorable CNS penetration capability, and that the newly modified P1 moiety may confer desirable features in designing novel anti-HIV-1 PIs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. NPASS: natural product activity and species source database for natural product research, discovery and tool development.

    Science.gov (United States)

    Zeng, Xian; Zhang, Peng; He, Weidong; Qin, Chu; Chen, Shangying; Tao, Lin; Wang, Yali; Tan, Ying; Gao, Dan; Wang, Bohua; Chen, Zhe; Chen, Weiping; Jiang, Yu Yang; Chen, Yu Zong

    2018-01-04

    There has been renewed interests in the exploration of natural products (NPs) for drug discovery, and continuous investigations of the therapeutic claims and mechanisms of traditional and herbal medicines. In-silico methods have been employed for facilitating these studies. These studies and the optimization of in-silico algorithms for NP applications can be facilitated by the quantitative activity and species source data of the NPs. A number of databases collectively provide the structural and other information of ∼470 000 NPs, including qualitative activity information for many NPs, but only ∼4000 NPs are with the experimental activity values. There is a need for the activity and species source data of more NPs. We therefore developed a new database, NPASS (Natural Product Activity and Species Source) to complement other databases by providing the experimental activity values and species sources of 35 032 NPs from 25 041 species targeting 5863 targets (2946 proteins, 1352 microbial species and 1227 cell-lines). NPASS contains 446 552 quantitative activity records (e.g. IC50, Ki, EC50, GI50 or MIC mainly in units of nM) of 222 092 NP-target pairs and 288 002 NP-species pairs. NPASS, http://bidd2.nus.edu.sg/NPASS/, is freely accessible with its contents searchable by keywords, physicochemical property range, structural similarity, species and target search facilities. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Toxicity Assessment of Atrazine and Related Triazine Compounds in the Microtox Assay, and Computational Modeling for Their Structure-Activity Relationship

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    Jerzy Leszczynski

    2000-10-01

    Full Text Available The triazines are a group of chemically similar herbicides including atrazine, cyanazine, and propazine, primarily used to control broadleaf weeds. About 64 to 80 million lbs of atrazine alone are used each year in the United States, making it one of the two most widely used pesticides in the country. All triazines are somewhat persistent in water and mobile in soil. They are among the most frequently detected pesticides in groundwater. They are considered as possible human carcinogens (Group C based on an increase in mammary gland tumors in female laboratory animals. In this research, we performed the Microtox Assay to investigate the acute toxicity of a significant number of triazines including atrazine, atraton, ametryne, bladex, prometryne, and propazine, and some of their degradation products including atrazine desethyl, atrazine deisopropyl, and didealkyled triazine. Tests were carried out as described by Azur Environmental [1]. The procedure measured the relative acute toxicity of triazines, producing data for the calculation of triazine concentrations effecting 50% reduction in bioluminescence (EC50s. Quantitative structure-activity relationships (QSAR were examined based on the molecular properties obtained from quantum mechanical predictions performed for each compound. Toxicity tests yielded EC50 values of 39.87, 273.20, 226.80, 36.96, 81.86, 82.68, 12.74, 11.80, and 78.50 mg/L for atrazine, propazine, prometryne, atraton, atrazine desethyl, atrazine deisopropyl, didealkylated triazine, ametryne, and bladex, respectively; indicating that ametryne was the most toxic chemical while propazine was the least toxic. QSAR evaluation resulted in a coefficient of determination (r2 of 0.86, indicating a good value of toxicity prediction based on the chemical structures/properties of tested triazines.

  10. Apamin-Sensitive Small Conductance Calcium-Activated Potassium Channels were Negatively Regulated by Captopril in Volume-Overload Heart Failure Rats.

    Science.gov (United States)

    Hongyuan, Bai; Xin, Dong; Jingwen, Zhang; Li, Gao; Yajuan, Ni

    2016-08-01

    In heart failure (HF), the malignant arrhythmias occur frequently; a study demonstrated that upregulation of I KAS resulted in recurrent spontaneous ventricular fibrillation in HF. However, the regulation of SK channels was poorly understood. The activation of SK channels depended on [Ca(2+)]i and PP2A; studies suggested that angiotensin II can regulate them. So, we hypothesized that in HF, the excess of angiotensin may regulate the SK channels and result in the remodeling of SK channels. To test the hypothesis, we used volume-overload-induced HF rat model, treated with captopril, performed whole-cell patch clamp to record apamin-sensitive currents (I KAS), and I-V curve was studied. The sensitivity of I KAS to [Ca(2+)]i was also explored by setting various [Ca(2+)]i (10, 100, 500, 900, 1000, and 10,000 nM), and the steady-state Ca(2+) response of I KAS was attained and performed Hill fitting with the equation (y = 1/[1 + (EC50/x) (n) ]). Immunofluorescent staining, real-time PCR, Western blot were also carried out to furtherly investigate the underlying molecular mechanisms of the regulation. Captopril significantly decreased the mean density of I KAS when [Ca(2+)]i was 500, 900, 1000, and 10000 nM. The Hill fitting showed significantly different EC50 values and the Hill coefficients and showed captopril significantly shifted rightward the steady-state Ca(2+) response of I KAS. The results of real-time PCR and Western blot demonstrated captopril decreased the mRNA and protein expression of SK3 channels. Captopril significantly downregulated the sensitivity of SK channels to [Ca(2+)]i and the SK3 channels expression in HF, and reversed the SK channels remodeling.

  11. Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea.

    Science.gov (United States)

    Anderson, W Gary; Leprince, Jérôme; Conlon, J Michael

    2008-08-01

    A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.

  12. Antioxidant activity of oregano essential oil (Origanum vulgare L.

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    Stanojević, Lj.P.

    2016-12-01

    Full Text Available Essential oil obtained from oregano (Origanum vulgare L. by Clevenger-type hydrodistillation and hydromodulus 1:10 m/v during 180 minutes, has been investigated in this work. Qualitative and quantitative composition of the oil was determined by GC-MS and GC-FID spectrometry. Antioxidant activity of the obtained oil was examined spectrophotometrically by DPPH test (after 20, 30, 45 and 60 minutes of incubation and TBA-MDA assay. The yield of essential oil was 4.1 mL/100 g of plant material. Seven components were identified: α-thujene, myrcene, α-terpinene, o-cymene, γ-terpinene, thymol and carvacrol. The major components were thymol (45% and carvacrol (37.4%. Oil incubated for 60 minutes has shown the best antioxidant activity according to DPPH test. The concentrations of essential oil, required for neutralization of 50% of initial DPPH radical concentration (EC50, were 0.761, 0.590, 0.360 and 0.326 mg/mL, after 20, 30, 45 and 60 minutes of incubation, respectively. Lipid peroxidation inhibition of 92.3% was achieved by 1.35 mg/mL essential oil concentration. The results obtained indicate that oregano essential oil is a good source of natural antioxidants with potential application in food and pharmaceutical industries, as a safer alternative to the synthetic antioxidants.

  13. Evaluation of gastroprotective activity of Passiflora alata

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    André Wasicky

    Full Text Available AbstractPassiflora alata Curtis, Passifloraceae, is a liana popularly known in Brazil as ‘maracujá-doce’ that has been used for treating different illnesses. Its leaves are described in the Brazilian Pharmacopoeia, but the gastroprotective activity has never been investigated. In the present study a freeze-dried crude 60% ethanol–water extract of P. alata aerial parts was prepared. Total flavonoid content, expressed as vitexin, was 0.67% ± 0.01. The hemolytic activity was 32 units for P. alata, using Saponin (Merck® as reference. P. alata presented EC50 of 1061.2 ± 8.5 µg/ml in the 2,2-diphenyl-1-picryhydrazyl assay and 1076 ± 85 µmol Trolox/g in the Oxygen Radical Absorbance Capacity assay. P. alata, its solvent fractions and a P. alatananopreparation were investigated for gastroprotective activity. The test samples exhibited gastroprotective activity on HCl/ethanol induced gastric mucosal lesions in rats. P. alata at doses of 100, 200 and 400 mg/kg, using the necrotizing agent at 150 mmol/l, inhibited 100% of ulcer formation (compared to the negative control, while lansoprazole (30 mg/kg 77%. When tested against a more concentrated necrotizing agent (300 mmol/l, fractions of P. alata at 100 mg/kg reduced 57% (n-hexane, 34% (ethyl acetate and 72% (aqueous fraction the ulcer formation. In this assay, lansoprazole (30 mg/kg inhibited 47%. When encapsulated, P. alata inhibited ulcer formation at 55%, 94% and 90% for dosages of 25, 50 and 100 mg/kg. These results suggest the potential use of P. alata as a gastroprotective herbal medicine.

  14. Comparative antitumor and anti-proliferative activities of Hippophae rhamnoides L. leaves extracts

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    Javid Ali

    2015-03-01

    Full Text Available Objective: To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform and n-hexane extracts of Hippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens with three different concentrations of test samples (10, 100 and 1 000 mg/L. Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8% was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated in n-hexane extract. The difference in tumor and cell inhibition (% may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions: Our finding showed that Hippophae rhamnoides leaves are a potent natural source of antitumor and antiproliferative agent.

  15. Antibacterial and antioxidant activities and acute toxicity of Bumelia sartorum Mart., Sapotaceae, a Brazilian medicinal plant

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    Halliny S. Ruela

    2011-03-01

    Full Text Available In order to validate the Bumelia sartorum Mart., Sapotaceae, traditional use for infection diseases, this study evaluates the antibacterial activity of the stem bark fractions against methicillin-sensitive (MSSA and methicillin-resistant (MRSA Staphylococcus aureus strains by using the agar dilution method and reported as MIC (minimal inhibitory concentration. In addition, the DPPH scavenging activity of these fractions was measured and the chemical composition and acute toxicity of the active fraction were also determined. The ethyl acetate (EtOAc extract was chemically analyzed by LC/MS, direct ionization APCI/MS, ¹H NMR and 13C-NMR. All fractions, except butanol extract, presented high antioxidant activity, especially the methanol and the EtOAc extracts, which showed EC50 values (5.67 and 5.30 µg/mL, respectively considerably lower than the Gingko-standard EGb 761® (38.58 µg/mL. The antibacterial activity against S. aureus strains was observed in EtOAc (MIC 256-512 µg/mL, which showed a very low toxicity. The chemical study of this fraction revealed the abundant presence of polyphenolic compounds. The antibacterial and antioxidant activities reported in this paper for EtOAc extract from B. sartorum and the low toxicity of this fraction opens the possibility that it could be helpful for the developing of new antibacterial agents for treating S. aureus infections.

  16. Antioxidant Activities of Hydrolysates of Arca Subcrenata Prepared with Three Proteases

    Science.gov (United States)

    Song, Liyan; Li, Tingfei; Yu, Rongmin; Yan, Chunyan; Ren, Shengfang; Zhao, Yu

    2008-01-01

    In order to get products with antioxidant activity from Arca subcrenata Lischke, the optimal hydrolase and hydrolysis conditions were investigated in the paper. Three proteases (neutrase, alcalase and papain) were applied to hydrolyze the homogenate of A. subcrenata. An orthogonal design was used to optimize hydrolysis conditions, and the pH-stat methods was used to determine the degree of hydrolysis. Viewed from the angle of reducing power, such as scavenging activities against α,α-diphenyl-β-picrylhydrazyl (DPPH) radical and hydrogen peroxide, the antioxidant activities of the alcalase hydrolysate (AH) were superior to neutrase hydrolysate (NH) and papain hydrolysate (PH), and its EC50 values in DPPH radical and hydrogen peroxide scavenging effect were 6.23 mg/ml and 19.09 mg/ml, respectively. Moreover, compared with products hydrolyzed by neutrase and papain, the molecular mass of AH was lower and its content of amino acid of peptides was higher. Therefore, alcalase was selected as the optimal enzyme to produce active ingredients since its hydrolysate exhibited the best antioxidant activity among them and possessed large amount of potential active peptides. PMID:19172198

  17. In vitro Antioxidant Activities of Sodium Zinc and Sodium Iron Chlorophyllins from Pine Needles

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    Ruzhen Zhan

    2014-01-01

    Full Text Available Chlorophyll was extracted from pine needles, and then sodium zinc chlorophyllin (SZC and sodium iron chlorophyllin (SIC were synthesised by saponification, purification and substitution reaction, using sodium copper chlorophyllin (SCC as a control. Their crystalline structures were verified by atomic absorbance spectroscopy, UV-VIS spectroscopy and HPLC. Moreover, their antioxidant activities were evaluated and compared with that of ascorbic acid through four biochemical assays: DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, reducing power, inhibition of β-carotene bleaching and O2– scavenging activity. SZC had better antioxidant properties at a lower dosage than SIC and SCC in all assays. In the β-carotene bleaching assay, EC50 of SZC, SIC and SCC was 0.04, 0.38 and 0.90 mg/mL, respectively, much lower than that of ascorbic acid (4.0 mg/mL. SZC showed a better result (p<0.05 than ascorbic acid in the O2 – scavenging activity assay. The results obtained from reducing power determination were also excellent: the absorbance values were all about 1.0 at 0.5 mg/mL, about half of that of ascorbic acid. In the investigation of DPPH radical scavenging activity, all chlorophyllins had lower activities than ascorbic acid. These results demonstrated the potential bioactivities of chlorophyll derivatives and supported their possible role in human health protection and disease prevention.

  18. Synthesis, antibacterial, antifungal and anti-HIV activities of norfloxacin mannich bases.

    Science.gov (United States)

    Pandeya, S N; Sriram, D; Nath, G; De Clercq, E

    2000-02-01

    Mannich bases of norfloxacin were synthesized by reacting them with formaldehyde and several isatin derivatives. Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis. Investigation of in vitro antimicrobial activity of compounds was done by the agar dilution method against 28 pathogenic bacteria, eight pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. The in vivo antibacterial efficacy of selected derivatives was determined using a mouse infection model. All the synthesized compounds are more active than norfloxacin against the 13 bacteria tested. The compounds are also more active than the standard drug clotrimazole against Histoplasma capsulatum. Two compounds S-8 and S-9 have shown inhibition against HIV-1 (III B) with EC(50) values of 11.3 and 13.9 microgram/mL, respectively. In the mouse protection test, two compounds S-4 (ED(50): 1.25 mg/kg) and S-9 (ED(50): 1.62 mg/kg) are more active than norfloxacin (ED(50): 6mg/kg). Among the compounds tested, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7[[N(4)-[5'-bromo-3'-(4'-amino-5'-trimethoxybenzylpyr imidin-2'-yl]-imino-1'-isatinyl]methyl]N(1)-piperazinyl]-3-q uinoline carboxylicacid (S-9) showed promising activity in all the three tests.

  19. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao.

    Science.gov (United States)

    Baharum, Zainal; Akim, Abdah Md; Taufiq-Yap, Yun Hin; Hamid, Roslida Abdul; Kasran, Rosmin

    2014-11-10

    The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50) was 358.3±7.0 µg/mL and total phenolic content was 22.0±1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4%±1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50)=41.4±3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

  20. Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors

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    Mohamad Ali Hijazi

    2017-01-01

    Full Text Available Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.

  1. Antioxidant and antiproliferative activities of phenolics isolated from fruits of Himalayan yellow raspberry (Rubus ellipticus).

    Science.gov (United States)

    Saini, Ritu; Dangwal, Koushalya; Singh, Himani; Garg, Veena

    2014-11-01

    Yellow Himalayan raspberry, a wild edible fruit, was analyzed for phenolic contents, and antioxidant, antibacterial and antiproliferative activities. Phenolics were extracted using 80 % aqueous solvents containing methanol, acidic methanol, acetone and acidic acetone. Our analysis revealed that the acidic acetone extracts recovered the highest level of total phenolics (899 mg GAE/100 g FW) and flavonoids (433.5 mg CE/100 g FW). Free radical scavenging activities (DPPH, ABTS, superoxide and linoleate hydroperoxide radicals) and ferric reducing activity were highest in the acetone and acidic acetone extracts. No metal chelating or antibacterial activity was detected in any of the extracts. Acetone and methanol extracts showed potent antiproliferative activity against human cervical cancer cells (C33A) with an EC50 of inhibition at 5.04 and 4. 9 mg/ml fruit concentration respectively, while showing no cytotoxicity to normal PBMCs cells. Therefore, the present study concluded that the yellow Himalayan raspberry is a potent source of phytochemicals having super antioxidant and potent antiproliferative activities.

  2. Comparison of Antioxidant and Antibacterial Activities of Free and Encapsulated Garlic Oil with Beta-cyclodextrin

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    Khadijeh Khoshtinat

    2016-10-01

    Full Text Available Background and Objectives: Application of garlic oil in food industry can be improved by encapsulation. There is no study about the formation of inclusion complex of garlic oil by beta-cyclodextrin. The aim of the present study is comparison of the antioxidant and antibacterial activities of free and encapsulated garlic oil with beta-cyclodextrin.Materials and Methods: Antioxidant activity was determined by 1, 1- diphenyl-2- picryl-hydrazyl assay, and antibacterial properties by agar well diffusion, minimum inhibitory concentration, minimum bactericidal concentration and bacterial growth assay. Statistical analysis was performed by Minitab statistical software.Results and conclusion: Garlic oil had poor antioxidant activity (EC50, 5222 µg ml-1 and EC50 because garlic oil/beta-cyclodextrin (containing 1495 µg ml-1 released garlic oil was achieved after 5 h and 25 min. Agar well diffusion showed no inhibition zone on Muller Hinton Agar for garlic oil and garlic oil/betacyclodextrin (with initial release (shaking at 150 rpm for 24 h at 37ºC and without initial release. Staphylococcus aureus was the most susceptible bacterium to garlic oil, and garlic oil/beta-cyclodextrin with and without initial release (minimum inhibitory concentration 10-5 , 10-4 and 10-3 % w v -1 , respectively; however, Bacillus cereus was the most resistant. The effect of initial release for garlic oil/betacyclodextrin on inhibiting the growth of all four bacteria was significant. There was no significant difference (P>0.05 between the inhibitory effect of garlic oil and garlic oil/beta-cyclodextrin with initial release on Staphylococcus aureus and Bacillus cereus, also Salmonella entrica and Escherichia coli. Garlic oil showed a weak antioxidant activity in 1, 1- diphenyl-2-picryl-hydrazyl assay. Garlic oil and its complex were not able to penetrate to the solid media; therefore, no inhibition zone and no antibacterial activity in the agar well diffusion assay were

  3. Chemical composition, antioxidant activity and in vitro antibacterial activity of Achillea wilhelmsii C. Koch essential oil on methicillin-susceptible and methicillin-resistant Staphylococcus aureus spp.

    Science.gov (United States)

    Alfatemi, Seyedeh Mahsan Hoseini; Rad, Javad Sharifi; Rad, Majid Sharifi; Mohsenzadeh, Sasan; da Silva, Jaime A Teixeira

    2015-02-01

    The present study investigated the chemical composition of the essential oil (EO) from aerial parts (flowering stage) of Achillea wilhelmsii C. Koch by GC-MS. In addition, the antioxidant activity of the EO as well as its antimicrobial activity against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA) strains was tested. Antioxidant activity was measured by the ability of the EO to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals while the antimicrobial activity was assessed by the disc-diffusion method. In total, 52 compounds were recognized, accounting for 97.33 % of the EO. The main compounds in the EO were carvacrol (22.49 %), dihydrocarvone (13.23 %), linalool (12 %), 1,8-cineol (11.42 %), camphene (8.31 %), thymol (5.28 %), camphor (3.71 %), pulegone (2.82 %) α-terpineol (2.11 %), bornyl acetate (1.14 %), and farganol (1.01 %). The EC 50 value of the EO was 0.01 and 0.08 mg/mL for the antioxidant and DPPH-scavenging ability, respectively. A. wilhelmsii EO affected methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA, but the impact was more effective on MSSA.

  4. In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination

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    Park Su-Jin

    2010-11-01

    Full Text Available Abstract Background Alpinia katsumadai (AK extracts and fractions were tested for in vitro antiviral activities against influenza virus type A, specially human A/PR/8/34 (H1N1 and avian A/Chicken/Korea/MS96/96 (H9N2, by means of time-of-addition experiments; pre-treatment, simultaneous treatment, and post treatment. Results In pre-treatment assay, the AK extracts and AK fractions did not show significant antiviral activity. During the simultaneous treatment assay, one AK extract and five AK fractions designated as AK-1 to AK-3, AK-5, AK-10, and AK-11 showed complete inhibition of virus infectivity against A/PR/8/34 (H1N1 and A/Chicken/Korea/MS96/96 (H9N2. The 50% effective inhibitory concentrations (EC50 of these one AK extracts and five AK fractions with exception of the AK-9 were from 0.8 ± 1.4 to 16.4 ± 4.5 μg/mL against A/PR/8/34 (H1N1. The two AK extracts and three AK fractions had EC50 values ranging from μg/mL against A/Chicken/Korea/MS96/96 (H9N2. By the hemagglutination inhibition (HI assay, the two AK extracts and five AK fractions completely inhibited viral adsorption onto chicken RBCs at less than 100 μg/mL against both A/PR/8/34 (H1N1 and A/Chicken/Korea/MS96/96 (H9N2. Interestingly, only AK-3 was found with inhibition for both viral attachment and viral replication after showing extended antiviral activity during the post treatment assay and quantitative real-time PCR. Conclusions These results suggest that AK extracts and fractions had strong anti-influenza virus activity that can inhibit viral attachment and/or viral replication, and may be used as viral prophylaxis.

  5. Assessment of antioxidant and cytotoxicity activities of saponin and crude extracts of Chlorophytum borivilianum.

    Science.gov (United States)

    Ashraf, Mehdi Farshad; Abd Aziz, Maheran; Stanslas, Johnson; Ismail, Ismanizan; Abdul Kadir, Mihdzar

    2013-01-01

    The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferrous ion chelating (FIC), and β -carotene bleaching (BCB) activity) of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 ± 111 mg AA/100 g) and bleaching activity (IC50 = 0.7 mg mL(-1)), while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL(-1)). Cytotoxicity evaluation of crude extract and total saponin fraction against MCF-7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line.

  6. Chemical Composition and Biological Activities of Mono- and Heterofloral Bee Pollen of Different Geographical Origins

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    Jucilene Silva Araújo

    2017-04-01

    Full Text Available Recent research shows variations in pollen chemical constituents and, consequently, in their therapeutic properties. Mono and multifloral bee pollen extracts were investigated for antioxidant and enzyme inhibitory activity properties, phenolic compounds and fatty acid composition. Generally, Eucalyptus spp. and multifloral extracts exhibited potent inhibitory activity against α-amylase, acetylcholinesterase, tyrosinase, lipoxygenase, lipase and hyaluronidase. On the other hand, Miconia spp. demonstrated higher antihemolytic activity. Cocos nucifera and Miconia spp. extracts exhibited important antioxidant properties in the different assays (ABTS, DPPH, β-carotene/linoleic acid and reducing power. Moreover, these extracts had greater amounts of total phenols and flavonoids in comparison to others. The increase in antioxidant activity (decrease in EC50 values was accompanied by an increase in the amount of total phenols in the extracts. The pollen extracts contained linoleic acid and α-linolenic acid as major fatty acids, followed by palmitic acid, and oleic acid. In this study, differences were observed in both chemical constituents and biological activities of the samples related to the geographical and botanical origin of bee pollen.

  7. Antioxidant Activities of Hydrolysates of Arca Subcrenata Prepared with Three Proteases

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    Liyan Song

    2008-11-01

    Full Text Available In order to get products with antioxidant activity from Arca subcrenata Lischke, the optimal hydrolase and hydrolysis conditionswere investigated in the paper. Three proteases (neutrase, alcalase and papain were applied to hydrolyze the homogenate of A. subcrenata. An orthogonaldesign was used to optimize hydrolysis conditions, and the pH-stat methods was used to determine the degree of hydrolysis. Viewed from the angle ofreducing power, such as scavenging activities against α,α-diphenyl-β-picrylhydrazyl (DPPH radical and hydrogen peroxide, the antioxidantactivities of the alcalase hydrolysate (AH were superior to neutrase hydrolysate (NH and papain hydrolysate (PH, and its EC50 values in DPPHradical and hydrogen peroxide scavenging effect were 6.23 mg/ml and 19.09 mg/ml, respectively. Moreover, compared with products hydrolyzed byneutrase and papain, the molecular mass of AH was lower and its content ofamino acid of peptides was higher. Therefore, alcalase was selected as theoptimal enzyme to produce active ingredients since its hydrolysate exhibitedthe best antioxidant activity among them and possessed large amount ofpotential active peptides.

  8. Preparation and Characterizations of Chitosan/Citral Nanoemulsions and their Antimicrobial Activity

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    Gehan I. Kh. Marei

    2018-03-01

    Full Text Available Background and Objective: The antimicrobial activity of essential oils has been long recognized, however, they easily evaporate and/or decompose during preparation, owing to direct exposure to heat, pressure and light. The current study deals with the formulation and characterization of bio-based oil in water nanoemulsions and their antimicrobial activity against plant pathogens.Material and Methods: Citral oil and low molecular weight chitosan were used for preparation of nanoemulsions in the presence of sodium tripolyphosphate. Nanoemulsions were prepared by adding dropwise citral at different ratios into an aqueous solution containing chitosan, sodium tripolyphosphate and surfactant with continuous stirring and then ultrasonication. The success of formulation was confirmed by dynamic light scattering and scanning electron microscopy techniques. Physical stability and viscosity were investigated in details. The antimicrobial activity was evaluated against Erwinia carotovora, Aspergillus niger and Rhizopus stolonifer. Results and Conclusion: The nanoemulsions had a polydispersity index ranged from 0.508 to 0.614 and particle size from 27 to 1283 nm. The highest antimicrobial activity was observed with F1 formulation (EC50 = 23, 278 and 221 mg L-1, against Erwinia carotovora, Aspergillus niger and Rhizopus stolonifer, respectively. Based on the antimicrobial activity, the prepared chitosan/citral nanoemulsions can be a cost-effective way to protect crops from microbial pathogens. Because such formulations contain bioactive products, the development of resistant pathogens can be delayed.Conflict of Interest: The authors declare no conflict of interest. 

  9. Effect of carbaryl (carbamate insecticide) on acetylcholinesterase activity of two strains of Daphnia magna (Crustacea, Cladocera).

    Science.gov (United States)

    Toumi, Hela; Bejaoui, Mustapha; Touaylia, Samir; Burga Perez, Karen F; Ferard, Jean François

    2016-11-01

    The present study was designed to investigate the effect of carbaryl (carbamate insecticide) on the acetylcholinesterase activity in two strains (same clone A) of the crustacean cladoceran Daphnia magna. Four carbaryl concentrations (0.4, 0.9, 1.8 and 3.7 µg L(-1)) were compared against control AChE activity. Our results showed that after 48 h of carbaryl exposure, all treatments induced a significant decrease of AChE activities whatever the two considered strains. However, different responses were registered in terms of lowest observed effect concentrations (LOEC: 0.4 µg L(-1) for strain 1 and 0.9 µg L(-1) for strains 2) revealing differences in sensitivity among the two tested strains of D. magna. These results suggest that after carbaryl exposure, the AChE activity responses can be also used as a biomarker of susceptibility. Moreover, our results show that strain1 is less sensitive than strain 2 in terms of IC50-48 h of AChE activity. Comparing the EC50-48 h of standard ecotoxicity test and IC50-48 h of AChE inhibition, there is the same order of sensitivity with both strains.

  10. Assessment of Antioxidant and Cytotoxicity Activities of Saponin and Crude Extracts of Chlorophytum borivilianum

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    Mehdi Farshad Ashraf

    2013-01-01

    Full Text Available The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH, ferrous ion chelating (FIC, and β-carotene bleaching (BCB activity of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 ± 111 mg AA/100 g and bleaching activity (IC50 = 0.7 mg mL−1, while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL−1. Cytotoxicity evaluation of crude extract and total saponin fraction against MCF-7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide (MTT cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line.

  11. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

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    Shiyao Jiang

    2017-02-01

    Full Text Available Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  12. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner.

    Science.gov (United States)

    Jiang, Shiyao; Tsikolia, Maia; Bernier, Ulrich R; Bloomquist, Jeffrey R

    2017-02-06

    Mosquitoes, such as Aedes aegypti and Anopheles gambiae , are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC 50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti , fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD 50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti . These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl -1675 strains, with EC 50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl , the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  13. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics.

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    Gupta, Kajal; Singh, Sameer; van Hoek, Monique L

    2015-08-24

    Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA-1A and ATRA-2) containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 = 0.05 μg/mL). High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed synergism

  14. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics

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    Kajal Gupta

    2015-08-01

    Full Text Available Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP. Two synthetic 11-residue peptides (ATRA-1A and ATRA-2 containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4. We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost, making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP (EC50 = 0.05 μg/mL. High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed

  15. Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3.

    Science.gov (United States)

    Wright, Paul D; Veale, Emma L; McCoull, David; Tickle, David C; Large, Jonathan M; Ococks, Emma; Gothard, Gemma; Kettleborough, Catherine; Mathie, Alistair; Jerman, Jeffrey

    2017-11-04

    Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Comparative distribution and in vitro activities of the urotensin II-related peptides URP1 and URP2 in zebrafish: evidence for their colocalization in spinal cerebrospinal fluid-contacting neurons.

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    Feng B Quan

    Full Text Available Urotensin II (UII is an evolutionarily conserved neuropeptide initially isolated from teleost fish on the basis of its smooth muscle-contracting activity. Subsequent studies have demonstrated the occurrence of several UII-related peptides (URPs, such that the UII family is now known to include four paralogue genes called UII, URP, URP1 and URP2. These genes probably arose through the two rounds of whole genome duplication that occurred during early vertebrate evolution. URP has been identified both in tetrapods and teleosts. In contrast, URP1 and URP2 have only been observed in ray-finned and cartilaginous fishes, suggesting that both genes were lost in the tetrapod lineage. In the present study, the distribution of urp1 mRNA compared to urp2 mRNA is reported in the central nervous system of zebrafish. In the spinal cord, urp1 and urp2 mRNAs were mainly colocalized in the same cells. These cells were also shown to be GABAergic and express the gene encoding the polycystic kidney disease 2-like 1 (pkd2l1 channel, indicating that they likely correspond to cerebrospinal fluid-contacting neurons. In the hindbrain, urp1-expressing cells were found in the intermediate reticular formation and the glossopharyngeal-vagal motor nerve nuclei. We also showed that synthetic URP1 and URP2 were able to induce intracellular calcium mobilization in human UII receptor (hUT-transfected CHO cells with similar potencies (pEC50=7.99 and 7.52, respectively albeit at slightly lower potencies than human UII and mammalian URP (pEC50=9.44 and 8.61, respectively. The functional redundancy of URP1 and URP2 as well as the colocalization of their mRNAs in the spinal cord suggest the robustness of this peptidic system and its physiological importance in zebrafish.

  17. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Science.gov (United States)

    Behbahani, Mandana

    2014-01-01

    Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs) used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR) assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50) values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  18. Antiviral activity of polysaccharide extract from Laminaria japonica against respiratory syncytial virus.

    Science.gov (United States)

    Cao, Yin-Guang; Hao, Yu; Li, Zhi-Hui; Liu, Shun-Tao; Wang, Le-Xin

    2016-12-01

    This study was designed to investigate the inhibition activity of polysaccharide extract from Laminaria japonica against RSV. The polysaccharide from Laminaria japonica was isolated by ethanol precipitation. HEK293 cells were infected with RVS, and the antiviral activity of polysaccharide extract against RSV in host cells was tested. By using ELISA and western blot assay, the expression level of IFN-α and IRF3 and their functional roles in polysaccharide-mediated antiviral activity against RSV were investigated. The polysaccharide extract from Laminaria japonica had low toxicity to HEK293 cell. The TC50 to HEK293 cells was up to 1.76mg/mL. Furthermore, the EC50 of polysaccharide extract to RSV was 5.27μg/mL, and TI was 334. The polysaccharide extract improved IRF-3 expression which promoted the level of IFN-α. Polysaccharide extract from Laminaria japonica elicits antiviral activity against RSV by up-regulation of IRF3 signaling-mediated IFN-α production. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels

    Science.gov (United States)

    Fujita, F; Moriyama, T; Higashi, T; Shima, A; Tominaga, M

    2007-01-01

    Background and purpose: Parabens are commonly added in pharmaceutical, cosmetic and food products because of their wide antibacterial properties, low toxicity, inertness and chemical stability, although the molecular mechanism of their antibacterial effect is not fully understood. Some agonists of the transient receptor potential (TRP) A1 channels are known to have strong antibacterial activities. Therefore, a series of experiments was conducted to find out the effects of parabens on TRP channels expressed in sensory neurons, particularly the TRPA1 channels. Experimental approach: Effects of parabens, especially of methyl p-hydroxybenzoate (methyl paraben) on TRP channel activities were examined using Ca2+-imaging and patch-clamp methods. In addition, an involvement of methyl paraben in the development of pain-related behavior in mice was investigated. Key results: Methyl paraben specifically activated TRPA1 in both HEK293 cells expressing TRPA1 and in mouse sensory neurons with an EC50 value of 4.4 mM, an attainable concentration in methyl paraben-containing products. Methyl paraben caused pain-related behavior in mice similar to that caused by allyl isothiocyanate, which was blocked by the TRP channel blocker, ruthenium red. Conclusions and implications: Our data indicate that methyl paraben is able to activate TRPA1 channels and can cause pain sensation. As such, methyl paraben provides a useful tool for investigating TRPA1 function and development of antinociceptive agents acting on TRPA1 channels. PMID:17351650

  20. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Directory of Open Access Journals (Sweden)

    Mandana Behbahani

    Full Text Available Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50 values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  1. Formulation of microspheres containing Crataegus monogyna Jacq. extract with free radical scavenging activity.

    Science.gov (United States)

    Lucconi, Giulia; Chlapanidas, Theodora; Martino, Emanuela; Gaggeri, Raffaella; Perteghella, Sara; Rossi, Daniela; Faragò, Silvio; Vigo, Daniele; Faustini, Massimo; Collina, Simona; Torre, Maria Luisa

    2014-02-01

    Extracts of Crataegus monogyna Jacq. (hawthorn) show an interesting free radical scavenging (FRS) effect, related to their flavonoids content. Unfortunately, their oral administration is affected by their low bioavailability. The aim of this work is to obtain a multiparticulate drug delivery system for hawthorn extracts for oral administration. The extracts from flowering tops (FL) or fruits (FR) of hawthorn were obtained with maceration, using ethanol as an extraction solvent, and their antioxidant activity was evaluated. FL extract showed the highest FRS activity (EC50 3.72 ± 1.21 µg/ml), so it was selected to prepare microparticulate systems by a spray-drying technique, which were characterized by granulometric analysis, scanning electron microscopy-energy dispersive X-ray spectroscopy, confocal fluorescence microscopy and hyperoside content. Antioxidant activity was evaluated before and after gastrointestinal transit in vitro simulation. Results indicate that the microparticulate systems maintained the antioxidant activity of hawthorn also after gastrointestinal transit in vitro simulation, exhibiting properties suitable for oral administration.

  2. Extraction optimization of polysaccharide from Zanthoxylum bungeanum using RSM and its antioxidant activity.

    Science.gov (United States)

    Li, Peiqin; Zhou, Ligang; Mou, Yan; Mao, Ziling

    2015-01-01

    Polysaccharide prepared from pericarp of Zanthoxylum bungeanum was proved to possess excellent antioxidant activities in vitro by using reducing ferric iron power, DPPH radical scavenging activity, chelating ferrous iron capacity, and hydroxyl radical scavenging activity assays in the present study. In those four antioxidant assay models, Z. bungeanum polysaccharide (ZBP) displayed prominent antioxidant activities with low EC50 values of 0.011, 0.021, 0.056 and 0.008 mg/mL, respectively. Moreover, the extraction process of ZBP was further optimized by response surface methodology combined with Box-Behnken design. The highest polysaccharide yield 13.96%, which agreed closely with the predicted yield 13.20%, was obtained under the optimal extraction conditions as follows: extraction temperature 89 °C, extraction time 3h, ratio of water volume (mL) to raw material weight (g) 29 (v/w), and extraction number two times. The present research not only provide theoretical basis for exploitation of natural polysaccharide antioxidants, but also establish the foundation of large-scale production and further system utilization of ZBP. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. In vitro anti-HIV-1 activity of the aqueous extract of Asterina pectinifera.

    Science.gov (United States)

    Karadeniz, Fatih; Karagozlu, Mustafa Zafer; Kong, Chang-Suk; Kim, Se-Kwon

    2011-03-01

    An aqueous extract of starfish, Asterina pectinifera, was investigated for its anti-HIV-1 efficiency in vitro on human T-cell lines. A. pectinifera significantly maintained the viability of HIV-infected cells as much as 86% of the untreated infected control cells at the non-toxic concentrations (0.05~4 mg/mL) in CEM-SS cells. Anti-HIV-1 activity of A. pectinifera extract was further supported by quantification of syncytia formation, reverse transcriptase activity and Western blot analysis in C8166, CEM-SS and H9 cells, respectively. Current results demonstrated a notable inhibition of HIV-1 induced syncytia formation and HIV-1 reverse transcriptase activity assay with EC50 of 0.71 mg/mL and 0.65 mg/mL, respectively. Moreover, A. pectinifera extract treatment decreased the production of p24 protein and gene expression of HIV-1 viral infection factor in a dose-dependent manner according to immunoblot and reverse transcription polymerase chain reaction analysis. In the light of current study, it can be concluded that A. pectinifera contains highly potential anti-HIV-1 components and a further investigation for active compound isolation is urged.

  4. New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.

    Science.gov (United States)

    Krečmerová, Marcela; Dračínský, Martin; Snoeck, Robert; Balzarini, Jan; Pomeisl, Karel; Andrei, Graciela

    2017-09-01

    New 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidine (PMEO-DAPy) and 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (PME-5-azaC) prodrugs were prepared with a pro-moiety consisting of carbonyloxymethyl esters (POM, POC), alkoxyalkyl esters, amino acid phosphoramidates and/or tyrosine. The activity of the prodrugs was evaluated in vitro against different virus families. None of the synthesized prodrugs demonstrated activity against RNA viruses but some of them proved active against herpesviruses [including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV)]. The bis(POC) and the bis(amino acid) phosphoramidate prodrugs of PMEO-DAPy inhibited herpesvirus replication at lower doses than the parent compound although the selectivity against HSV and VZV was only slightly improved compared to PMEO-DAPy. The mono-octadecyl ester of PME-5-azaC emerged as the most potent and selective PME-5-azaC prodrug against HSV, VZV and HCMV with EC 50 's of 0.15-1.12µM while PME-5-azaC only had marginal anti-herpesvirus activity. Although the bis(hexadecylamido-l-tyrosyl) and the bis(POM) esters of PME-5-azaC were also very potent anti-herpesvirus drugs, these were less selective than the mono-octadecyl ester prodrug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Design, Synthesis and Fungicidal Activity of 2-Substituted Phenyl-2-oxo-, 2-Hydroxy- and 2-Acyloxyethylsulfonamides

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    Minlong Wang

    2017-05-01

    Full Text Available Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl derivatives. A series of thirty-eight 2-substituted phenyl-2-oxo- III, 2-hydroxy- IV and 2-acyloxyethylsulfonamides V were obtained and their structures confirmed by IR, 1H-NMR, and elemental analysis. The in vitro and in vivo bioactivities against two Botrytis cinerea strains, DL-11 and HLD-15, which differ in their sensitivity to procymidone, were evaluated. The in vitro activity results showed that the EC50 values of compounds V-1 and V-9 were 0.10, 0.01 mg L−1 against the sensitive strain DL-11 and 3.32, 7.72 mg L−1 against the resistant strain HLD-15, respectively. For in vivo activity against B. cinerea, compound V-13 and V-14 showed better control effect than the commercial fungicides procymidone and pyrimethanil. The further in vitro bioassay showed that compounds III, IV and V had broad fungicidal spectra against different phytopathogenic fungi. Most of the title compounds showed high fungicidal activities, which could be used as lead compounds for further developing novel fungicidal compounds against Botrytis cinerea.

  6. Antifungal Activity and Biochemical Response of Cuminic Acid against Phytophthora capsici Leonian.

    Science.gov (United States)

    Wang, Yong; Sun, Yang; Zhang, Ying; Zhang, Xing; Feng, Juntao

    2016-06-11

    Phytophthora blight of pepper caused by Phytophthora capsici Leonian is a destructive disease throughout the world. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to the benzoic acid chemical class. In this study, the sensitivity and biochemical response of P. capsici to cuminic acid was determined. The mean EC50 (50% effective concentration) values for cuminic acid in inhibiting mycelial growth and zoospore germination of the 54 studied P. capsici isolates were 14.54 ± 5.23 μg/mL and 6.97 ± 2.82 μg/mL, respectively. After treatment with cuminic acid, mycelial morphology, sporangium formation and mycelial respiration were significantly influenced; cell membrane permeability and DNA content increased markedly, but pyruvic acid content, adenosine triphosphate (ATP) content, and ATPase activity decreased compared with the untreated control. In pot experiments, cuminic acid exhibited both protective and curative activity. Importantly, POD and PAL activity of the pepper leaves increased after being treated with cuminic acid. These indicated that cuminic acid not only showed antifungal activity, but also could improve the defense capacity of the plants. All the results suggested that cuminic acid exhibits the potential to be developed as a new phytochemical fungicide, and this information increases our understanding of the mechanism of action of cuminic acid against Phytophthora capsici.

  7. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

    Science.gov (United States)

    Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

    2014-01-01

    Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

  8. Phenylquinoxalinone CFTR activator as potential prosecretory therapy for constipation.

    Science.gov (United States)

    Cil, Onur; Phuan, Puay-Wah; Son, Jung-Ho; Zhu, Jie S; Ku, Colton K; Tabib, Niloufar Akhavan; Teuthorn, Andrew P; Ferrera, Loretta; Zachos, Nicholas C; Lin, Ruxian; Galietta, Luis J V; Donowitz, Mark; Kurth, Mark J; Verkman, Alan S

    2017-04-01

    Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that stimulated intestinal fluid secretion and normalized stool output in a mouse model of opioid-induced constipation. Here, we report phenylquinoxalinone structure-activity analysis, mechanism of action, animal efficacy data in acute and chronic models of constipation, and functional data in ex vivo primary cultured human enterocytes. Structure-activity analysis was done on 175 phenylquinoxalinone analogs, including 15 synthesized compounds. The most potent compound, CFTR act -J027, activated CFTR with EC 50 ∼ 200 nM, with patch-clamp analysis showing a linear CFTR current-voltage relationship with direct CFTR activation. CFTR act -J027 corrected reduced stool output and hydration in a mouse model of acute constipation produced by scopolamine and in a chronically constipated mouse strain (C3H/HeJ). Direct comparison with the approved prosecretory drugs lubiprostone and linaclotide showed substantially greater intestinal fluid secretion with CFTR act -J027, as well as greater efficacy in a constipation model. As evidence to support efficacy in human constipation, CFTR act -J027 increased transepithelial fluid transport in enteroids generated from normal human small intestine. Also, CFTR act -J027 was rapidly metabolized in vitro in human hepatic microsomes, suggesting minimal systemic exposure upon oral administration. These data establish structure-activity and mechanistic data for phenylquinoxalinone CFTR activators, and support their potential efficacy in human constipation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Antioxidant and α-glucosidase inhibitory activities of cucurbit fruit vegetables and identification of active and major constituents from phenolic-rich extracts of Lagenaria siceraria and Sechium edule.

    Science.gov (United States)

    Sulaiman, Shaida Fariza; Ooi, Kheng Leong; Supriatno

    2013-10-23

    Antioxidant and α-glucosidase activities and total phenolic contents (TPC) in sequential extracts of dried pulps from seven cucurbit fruit vegetables were determined for the first time. The highest TPC and metal chelating activity were obtained from the chloroform extracts of Luffa acutangula (28.04 ± 0.37 mg GAE/g extract) and Benincasa hispida (EC50 = 0.44 ± 0.03 mg/mL), respectively. The ethyl acetate extract of Sechium edule showed the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (951.73 ± 29.14 mM TE/g extract). The highest reducing and anti-α-glucosidase activities were shown by the methanol and ethyl acetate extracts of Momordica charantia (692.56 ± 43.38 mM AscAE/g extract; 66.64 ± 2.94%, respectively). The highest correlation (r = 0.99) was observed between the TPC and DPPH values of S. edule. Although caffeic acid was quantified as the major constituent in the methanol extract of Lagenaria siceraria , isoquercetin was found to be the main contributor to the activities. Gallic acid was identified as both the main and most active antioxidant constituent in the ethyl acetate extract of S. edule.

  10. Antioxidant Activities of Three Rubus Species Growing in Ethiopia ...

    African Journals Online (AJOL)

    80% methanol extract, and acetone and methanol soxhlet fractions of the three plants tested showed antioxidant activity in a concentration-dependent manner. The 80% methanolic extract of R. steudneri showed the strongest activity in the DPPH radical scavenging assay (IC50 = 6.5 mg/ml). In the deoxyribose degradation ...

  11. Reconfirmation of antimicrobial activity in the coelomic fluid of the ...

    Indian Academy of Sciences (India)

    The anion (DEAE-52) exchange effluent of the ECFPE was reported to have the strongest activity against P. aeruginosa amongst the three active fractions. The 20% acetonitrile eluate (AE) by Sep-Pak C18 cartridge was also tested and showed fair resistance against E. coli, P. aeruginosa and Arthrobacter sp., respectively.

  12. Novel trans-Ferulic Acid Derivatives Containing a Chalcone Moiety as Potential Activator for Plant Resistance Induction.

    Science.gov (United States)

    Gan, Xiuhai; Hu, Deyu; Wang, Yanjiao; Yu, Lu; Song, Baoan

    2017-06-07

    A series of novel trans-ferulic acid derivatives containing a chalcone moiety were designed and synthesized to induce plant resistance. Antiviral activities of the compounds were evaluated. Bioassay results demonstrated that compounds F3, F6, F17, and F27 showed remarkable curative, protective, and inactivating activities against tobacco mosaic virus (TMV). With a 50% effective concentration (EC 50 ) value of 98.78 μg mL -1 , compound F27 exhibited the best protective activity compared with trans-ferulic acid (328.6 μg mL -1 ), dufulin (385.6 μg mL -1 ), and ningnanmycin (241.3 μg mL -1 ). This protective ability was associated with potentiation of defense-related enzyme activity and activation of photosynthesis of tobacco at an early stage. This notion was confirmed by up-regulated expression of stress responses and photosynthesis regulating proteins. This work revealed that F27 can induce resistance and enhance plant tolerance to TMV infection. Hence, F27 can be considered as a novel activator for inducing plant resistance.

  13. Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41.

    Science.gov (United States)

    Zhou, Guangyan; Sofiyev, Vladimir; Kaur, Hardeep; Snyder, Beth A; Mankowski, Marie K; Hogan, Priscilla A; Ptak, Roger G; Gochin, Miriam

    2014-06-26

    We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure-activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and molecular properties. Thirty new compounds were evaluated in binding, cell-cell fusion, and viral replication assays. Below a 1 μM threshold, correlation between binding and biological activity was diminished, indicating an amphipathic requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 μM binding affinity and 0.2 μM EC50 against cell-cell fusion and live virus replication and was active against T20 resistant strains. Twenty-two compounds with the same connectivity displayed a consensus pose in docking calculations, with rank order matching the biological activity. The work provides insight into requirements for small molecule inhibition of HIV-1 fusion and demonstrates a potent low molecular weight fusion inhibitor.

  14. Structure–Activity Relationship Studies of Indole-Based Compounds as Small Molecule HIV-1 Fusion Inhibitors Targeting Glycoprotein 41

    Science.gov (United States)

    2015-01-01

    We previously described indole-containing compounds with the potential to inhibit HIV-1 fusion by targeting the hydrophobic pocket of transmembrane glycoprotein gp41. Here we report optimization and structure–activity relationship studies on the basic scaffold, defining the role of shape, contact surface area, and molecular properties. Thirty new compounds were evaluated in binding, cell–cell fusion, and viral replication assays. Below a 1 μM threshold, correlation between binding and biological activity was diminished, indicating an amphipathic requirement for activity in cells. The most active inhibitor 6j exhibited 0.6 μM binding affinity and 0.2 μM EC50 against cell–cell fusion and live virus replication and was active against T20 resistant strains. Twenty-two compounds with the same connectivity displayed a consensus pose in docking calculations, with rank order matching the biological activity. The work provides insight into requirements for small molecule inhibition of HIV-1 fusion and demonstrates a potent low molecular weight fusion inhibitor. PMID:24856833

  15. Anti-allergic, anti-inflammatory and antioxidant activities of the different extracts of Thai traditional remedy called prabchompoothaweep for allergic rhinitis treatment.

    Science.gov (United States)

    Jai-aue, Areeratna; Makchuchit, Sunita; Juckmeta, Thana; Itharat, Arunporn

    2014-08-01

    Prabchompoothaweep remedy (PT) has long been used in Thai traditional medicine to treat allergic rhinitis and asthma. It is composed of 23 plants. It is on National herbal drug list of Thailand, but there is no reportfor anti-allergic, anti-inflammatory and antioxidant activities. To investigate anti-allergic, anti-inflammatory and antioxidant activities of the crude extract from PTby different extraction method. The method of extract used was maceration in 95% ethanol and 50% ethanol; the residue of these extracts were continued extracted by boiling water, they obtained PTE95, PTE50, PTR95 andPTR50, respectively. The other method of extraction was boiling and drying by lyophilizer that obtained PTW Five crude extracts were determined anti- allergic activity by the inhibition of β-hexosaminidase release from RBL-2H3 cell lines, anti-inflammatory activity were determined by the inhibition ofnitric oxide (NO) production from RA W264. 7 cell lines induced by lipopolysaccharide (LPS) and antioxidant activity were tested by DPPH radical scavenging assay. PTE95 showed the most potent ofanti-allergic activity, anti-inflammatory activity and antioxidant activity (IC5 = 12.97, 22.51 and EC50 = 14.62 μg/ml, respectively). These results suggest that the method of extraction PT that showed the best anti-allergy, anti-inflamation and antioxidant activity was maceration in 95% ethanol.

  16. Design, synthesis, antiviral bioactivity and three-dimensional quantitative structure-activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety.

    Science.gov (United States)

    Wu, Zengxue; Zhang, Jian; Chen, Jixiang; Pan, Jianke; Zhao, Lei; Liu, Dengyue; Zhang, Awei; Chen, Jin; Hu, Deyu; Song, Baoan

    2017-10-01

    Ferulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities. Bioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC 50 values of 162.14, 114.61 and 255.49, 138.81 mg L -1 , respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L -1 ). The values of q 2 and r 2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities. Some of the title compounds demonstrated good antiviral activities. Three-dimensional quantitative structure-activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Enrichment of chelidonine from Chelidonium majus L. using macroporous resin and its antifungal activity.

    Science.gov (United States)

    Pan, Jialiang; Yang, Yang; Zhang, Rui; Yao, Hanwen; Ge, Kangkang; Zhang, Manyin; Ma, Ling

    2017-12-01

    Chelidonium majus L. (greater celandine) has been used as an herbal medicine for several centuries. This study investigated an efficient method to purify chelidonine from the extract of C. majus L. using macroporous adsorption resins and evaluated the antifungal activity of chelidonine against Botryosphaeria dothidea as a model strain. Static adsorption and desorption tests revealed that D101 was the optimal resin for chelidonine purification. Pseudo-second-order kinetics model and Freundlich equation model were the most suitable for evaluating the endothermic and spontaneous adsorption processes of chelidonine on D101. Dynamic adsorption and desorption tests on D101 columns showed that the concentration of chelidonine increased 14.16-fold, from 2.67% to 37.81%, with the recovery yield of 80.77%. The antifungal activity of enriched chelidonine products was studied with B. dothidea. The results showed that the EC 50 of crude extracts, enriched chelidonine products, and chelidonine standard against B. dothidea were 3.24mg/mL, 0.43mg/mL, and 0.77mg/mL, respectively. The result of antifungal activity test showed that chelidonine had the potential to be a useful antifungal agent. Moreover, the enrichment method of chelidonine was highly efficient, low cost, and harmless to the environment for industrial applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Composition, antimicrobial and free-radical scavenging activities of the essential oil of Plectranthus marrubatus.

    Science.gov (United States)

    Asres, Kaleab; Tadesse, Solomon; Mazumder, Avijit; Bucar, Franz

    2012-05-01

    Essential oil from the aerial part of Plectranthus marrubatus J. K. Morton (Lamiaceae), obtained by hydrodistillation was analyzed by gas chromatography/mass spectrometry (GC/MS) and evaluated for antimicrobial and free radical scavenging activities. Twenty-four compounds representing 99% of the total oil were identified. The major constituents were thymol, p-cymene and gamma-terpinene. The oil was tested against 21 bacterial and 4 fungal strains using the disc diffusion method and found to be active against a broad spectrum of pathogens including Gram-positive and Gram-negative bacteria as well as some fungal strains. The minimum inhibitory concentrations (MICs) of the oil against the bacterial strains tested ranged from 10 to 800 microg/mL, and from 400 to 800 microg/mL against the fungal strains employed. The in vitro antioxidant activity was assessed using 2,2-diphenyl-l-picrylhydrazil (DPPH) and showed a low EC50 value of 0.15 microl/mL. The study provides evidence for the broad-spectrum antimicrobial and antioxidant effect of Plectranthus marrubatus essential oil, and a possible explanation for its traditional use in the treatment of cold, fever, stomach disorder, diarrhea and as a skin cleaner.

  19. Antioxidant activity of ripe and unripe pepino fruit (Solanum muricatum Aiton).

    Science.gov (United States)

    Sudha, Govindan; Priya, Marimuthu Sangeetha; Shree, Rajan Babu Indhu; Vadivukkarasi, Sabapathy

    2012-11-01

    Ripe and unripe exotic pepino fruit were evaluated for antioxidant activity, total phenols, and flavonoid content. The antioxidant potency was investigated by employing various established in vitro systems, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2-2'-azinobis(3-ethylbenthiazoline-6-sulphonic acid (ABTS), hydroxyl radical scavenging, reducing power, ferrous ion chelation, ferric reducing antioxidant power (FRAP), and lipid peroxidation. The EC(50) values of ripe ethanolic extract on DPPH radical, reducing power, ferrous ion chelation, ABTS radical, FRAP, hydroxyl radical, lipid peroxidation (brain), and lipid peroxidation (liver) were obtained to be 2.20, 2.81, fruit extract were noted to be 3.75, 3.40, 11.25, 40.12, 9.75, 0.80, 1.91, and 0.63 mg/mL, respectively. Ripe fruit exhibited the highest values of antioxidant activity in all the scavenging assays except for hydroxyl radical scavenging assay. Ripe pepino had higher total phenol and flavonoid content than unripe fruit. This study suggests that possible mechanism of the biological activities may be due to free radical scavenging and antioxidant characteristics, which may be due to the presence of polyphenols in the fruit extracts. The ripe and unripe pepino fruit have excellent antioxidant properties, so the results obtained in this study clearly indicate that pepino fruit has a significant potential to use as a natural antioxidant agent and possibly as a food supplement. © 2012 Institute of Food Technologists®

  20. Response of soil microbial activities and microbial community structure to vanadium stress.

    Science.gov (United States)

    Xiao, Xi-Yuan; Wang, Ming-Wei; Zhu, Hui-Wen; Guo, Zhao-Hui; Han, Xiao-Qing; Zeng, Peng

    2017-08-01

    High levels of vanadium (V) have long-term, hazardous impacts on soil ecosystems and biological processes. In the present study, the effects of V on soil enzymatic activities, basal respiration (BR), microbial biomass carbon (MBC), and the microbial community structure were investigated through 12-week greenhouse incubation experiments. The results showed that V content affected soil dehydrogenase activity (DHA), BR, and MBC, while urease activity (UA) was less sensitive to V stress. The average median effective concentration (EC 50 ) thresholds of V were predicted using a log-logistic dose-response model, and they were 362mgV/kg soil for BR and 417mgV/kg soil for DHA. BR and DHA were more sensitive to V addition and could be used as biological indicators for soil V pollution. According to a polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis, the structural diversity of the microbial community decreased for soil V contents ranged between 254 and 1104mg/kg after 1 week of incubation. As the incubation time increased, the diversity of the soil microbial community structure increased for V contents ranged between 354 and 1104mg/kg, indicating that some new V-tolerant bacterial species might have replicated under these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cytotoxic, virucidal, and antiviral activity of South American plant and algae extracts.

    Science.gov (United States)

    Faral-Tello, Paula; Mirazo, Santiago; Dutra, Carmelo; Pérez, Andrés; Geis-Asteggiante, Lucía; Frabasile, Sandra; Koncke, Elina; Davyt, Danilo; Cavallaro, Lucía; Heinzen, Horacio; Arbiza, Juan

    2012-01-01

    Herpes simplex virus type 1 (HSV-1) infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC(50)) values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI) obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  2. Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of liver X receptor-β.

    Science.gov (United States)

    Hoang, Minh-Hien; Jia, Yaoyao; Mok, Boram; Jun, Hee-jin; Hwang, Kwang-Yeon; Lee, Sung-Joon

    2015-08-01

    Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and glucose metabolism. However, its molecular mechanisms of action and target proteins have remained elusive, probably due to the involvement of multiple proteins. This study investigated the molecular targets of kaempferol. Ligand binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved fluorescence resonance energy transfer and surface plasmon resonance analyses. Kaempferol directly binds to and induces the transactivation of LXRs, with stronger specificity for the β-subtype (EC50 = 0.33 μM). The oral administration of kaempferol in apolipoprotein-E-deficient mice (150 mg/day/kg body weight) significantly reduced plasma glucose and increased high-density lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle-fed control. Kaempferol also reduced plasma triglyceride concentrations and did not cause liver steatosis, a common side effect of potent LXR activation. In immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol regulatory element-binding protein-1 (SREBP-1). Our results show that the suppression of SREBP-1 activity and the selectivity for LXR-β over LXR-α by kaempferol contribute to the reductions of plasma and hepatic triglyceride concentrations in mice fed kaempferol. They also suggest that kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Flavonoids as Vasorelaxant Agents: Synthesis, Biological Evaluation and Quantitative Structure Activities Relationship (QSAR Studies

    Directory of Open Access Journals (Sweden)

    Yongzhou Hu

    2011-09-01

    Full Text Available A series of 2-(2-diethylamino-ethoxychalcone and 6-prenyl(or its isomers-flavanones 10a,b and 11a–g were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pretreated with 1 μM phenylephrine (PE. Several compounds showed potent vasorelaxant activities. Compound 10a (EC50 = 7.6 μM, Emax = 93.1%, the most potent one, would be a promising structural template for development of novel and more efficient vasodilators. Further, 2D-QSAR analysis of compounds 10a,b and 11c-e as well as thirty previously synthesized flavonoids 1-3 and 12-38 using Enhanced Replacement Method-Multiple Linear Regression (ERM-MLR was further performed based on an optimal set of molecular descriptors (H5m, SIC2, DISPe, Mor03u and L3m, leading to a reliable model with good predictive ability (Rtrain2 = 0.839, Qloo2 = 0.733 and Rtest2 = 0.804. The results provide good insights into the structure- activity relationships of the target compounds.

  4. Mechanism of action of a novel human ether-a-go-go-related gene channel activator

    DEFF Research Database (Denmark)

    Casis, Oscar; Olesen, Søren-Peter; Sanguinetti, Michael C

    2005-01-01

    1,3-Bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is a newly discovered activator of human ether-a-go-go-related gene (hERG) K(+) channels. Here, we characterize the effects of this compound on cloned hERG channels heterologously expressed in Xenopus laevis oocytes. When assessed with 2-s...... depolarizations, NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and voltage-dependent manner with an EC(50) of 10.4 microM at -10 mV. The fully activated current-voltage relationship revealed that the drug increased outward but not inward currents, consistent with altered inactivation...... gating. NS1643 shifted the voltage dependence of inactivation by +21 mV at 10 microM and +35 mV at 30 microM, but it did not alter the voltage dependence of activation of hERG channels. The effects of the drug on three inactivation-deficient hERG mutant channels (S620T, S631A, and G628C/S631C) were...

  5. Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: effect of alpha-1 adrenergic activation

    Energy Technology Data Exchange (ETDEWEB)

    Villalobos-Molina, R.; Uc, M.; Hong, E.; Garcia-Sainz, J.A.

    1982-07-01

    Activation of rabbit aortic strips with alpha adrenergic agonists increased the labeling (with (/sup 32/P)Pi) of phosphatidylinositol (PI) and phosphatidic acid and contracted the vascular preparations in dose-related fashion. Epinephrine, norepinephrine and methoxamine produced maximal effects, whereas clonidine behaved as partial agonist and B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazole-(5,4-d) azepin dihydrochloride) was almost without activity in the two experimental models used. Phenylephrine was a full agonist in producing contraction, but failed to elicit the maximal increase in PI labeling. The EC50 values to produce contraction of aortic strips were lower for all agonists than those required to increase the incorporation of radioactive phosphate into PI, but there was a good correlation between the two sets of data. The increased PI labeling and contraction of aortic strips induced by epinephrine were antagonized by prazosin and yohimbine in dose-related fashion, but the first alpha blocker was about three orders of magnitude more potent than the second in antagonizing the two effects. The present results indicate that both stimulation of PI labeling and contraction are mediated through activation of alpha-1 adrenoceptors in rabbit aorta.

  6. Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

    Directory of Open Access Journals (Sweden)

    Paula Faral-Tello

    2012-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50 values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  7. Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: effect of alpha-1 adrenergic activation

    International Nuclear Information System (INIS)

    Villalobos-Molina, R.; Uc, M.; Hong, E.; Garcia-Sainz, J.A.

    1982-01-01

    Activation of rabbit aortic strips with alpha adrenergic agonists increased the labeling (with [ 32 P]Pi) of phosphatidylinositol (PI) and phosphatidic acid and contracted the vascular preparations in dose-related fashion. Epinephrine, norepinephrine and methoxamine produced maximal effects, whereas clonidine behaved as partial agonist and B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazole-[5,4-d] azepin dihydrochloride) was almost without activity in the two experimental models used. Phenylephrine was a full agonist in producing contraction, but failed to elicit the maximal increase in PI labeling. The EC50 values to produce contraction of aortic strips were lower for all agonists than those required to increase the incorporation of radioactive phosphate into PI, but there was a good correlation between the two sets of data. The increased PI labeling and contraction of aortic strips induced by epinephrine were antagonized by prazosin and yohimbine in dose-related fashion, but the first alpha blocker was about three orders of magnitude more potent than the second in antagonizing the two effects. The present results indicate that both stimulation of PI labeling and contraction are mediated through activation of alpha-1 adrenoceptors in rabbit aorta

  8. Structural characterization, α-glucosidase inhibitory and DPPH scavenging activities of polysaccharides from guava.

    Science.gov (United States)

    Zhang, Ziling; Kong, Fansheng; Ni, Hui; Mo, Zhixian; Wan, Jian-Bo; Hua, Dehong; Yan, Chunyan

    2016-06-25

    To explore the chemicals responsible for the health benefits of guava, water-soluble polysaccharides were extracted including GP90 and P90. They exhibited excellent α-glucosidase inhibition activity with an EC50 of 2.27μg/mL and 0.18mg/mL. This suggests that their activities were 1379- and 17-fold higher than the positive control. The DPPH scavenging activities of GP90 was even higher than Vc at some concentrations. Upon further isolation, a novel polysaccharide termed GB90-1B was obtained. Monosaccharide analysis, methylation analysis, and NMR were used to analyze the structural characterization of GB90-1B. Structural analysis revealed that its backbone consisted of (1→5)-linked-α-l-arabinose, (1→2,3,5)-linked-α-l-arabinose and (1→3)-linked-α-l-arabinose. Branch linkages included (1→6)-linked-α-d-glucose, (1→)-linked-α-d-glucose and (1→)-linked-α-l-arabinose. The structure of the repeating unit of GP90-1B was predicted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Potential cow milk xanthine oxidase inhibitory and antioxidant activity of selected phenolic acid derivatives.

    Science.gov (United States)

    Nile, Shivraj Hariram; Keum, Young Soo; Nile, Arti Shivraj; Kwon, Young Deuk; Kim, Doo Hwan

    2018-01-01

    Xanthine oxidase (XO) found in all mammals and excess activity leads to urolithiasis. The cow milk XO was purified to 305-fold with a specific activity of 8.76 EU/mg and overall yield of 87% by using DEAE-Sepharose chromatography. The phenolics showed potent XO inhibitory effect with K i , P1 (0.412), P2 (0.632), P3 (0.585), P4 (0.886), P5 (1.633), P6 (0.503), P7 (2.882), P8 (3.761), P9 (4.487), and P10 (5.841) μM. The phenolics P9 and P10 exhibited uncompetitive inhibition; the phenolics P1, P2, P3, P4, and P6 showed competitive inhibition, and other phenolic acids showed noncompetitive inhibition. The studied phenolic compounds showed potent antioxidant activity and expressed as EC 50 , ranged from, DPPH (4.2-25.8 μg mL -1 ), ABTS (10.2-42.5 mmol TE 100 g -1 ), and FRAP (6.3-36.8 mol Fe (II) 100 g -1 ). The results obtained from this study might be utilized for design of XO inhibitors and as antigout agent. © 2017 Wiley Periodicals, Inc.

  10. Evaluation of antiherpetic activity of crude extract and fractions of Avicenna marina, in vitro.

    Science.gov (United States)

    Behbahani, Mandana; Zadeh, Mehrnaz Shanehsaz; Mohabatkar, Hassan

    2013-03-01

    This study was carried out to check antiherpetic substances of crude methanol leaf extract of Avicenna marina and its column chromatographic fractions. Herpes simplex virus 2 (HSV-2) is a harmful pathogen especially in highly susceptible individuals. The antiherpetic activity of crude methanol extract and sub-fractions was performed in different concentrations (20, 2, 0.2, and 0.02μg/ml) by use of plaque-forming unit (PFU) assay and real time polymerase chain reaction (PCR) assay. The most active fraction analyzed by NMR contained luteolin 7-O-methylether 3'-O-beta-d-glucoside (LMEG). The other active fraction was detected by HPLC as luteolin. The apparent effective concentrations for 50% plaque reduction (EC50) of crude methanol extract, LMEG, luteolin and ACV were 10, 5, 16.6 and 2.97μg/ml, respectively. The three extracts showed no cytotoxic effect on Vero cell line at concentrations of 32μg/ml or below. According to the consequences of time-of-addition studies, antiherpetic compound LMEG exerted an inhibitory effect on the early stage of HSV-2 infection during which it was added. In conclusion, LMEG isolated from A. marina could probably inhibit HSV attachment to the cell membrane and its entry into the cell. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Ovicidal activity of succinic acid isolated from sisal waste (Agave sisalana against gastrointestinal nematodes of goats

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    Nathália Silva de Souza Santos

    Full Text Available ABSTRACT: This study was conducted to evaluate the in vitro anthelmintic activity of the succinic acid (SA isolated from sisal waste against gastrointestinal nematodes of goats, using the egg hatching and larvae motility assays. In addition, potential cytotoxicity of SA on Vero cell cultures was investigated by means of MTT (3-4,5-dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide test. The SA induced a significant inhibition of egg hatching (P<0.05 at all concentrations tested (60 to 250µg mL-1, and the concentrations to inhibit 50% (EC50 and 90% (EC90 values (mean ± standard deviation were 90.3±2.8 and 130.6±3.5µg mL-1, respectively. The SA has not shown larvicidal activity. The SA was less toxic to the Vero cells, with the mean percentage of cell viability equal to 85±6.2% at the concentration of 130µg mL-1. The results suggested that SA has potential anthelmintic effect; although, more research is needed to confirm its activity in vivo.

  12. Two Naturally Occurring Terpenes, Dehydrocostuslactone and Costunolide, Decrease Intracellular GSH Content and Inhibit STAT3 Activation

    Science.gov (United States)

    Butturini, Elena; Cavalieri, Elisabetta; Carcereri de Prati, Alessandra; Darra, Elena; Rigo, Antonella; Shoji, Kazuo; Murayama, Norie; Yamazaki, Hiroshi; Watanabe, Yasuo; Suzuki, Hisanori; Mariotto, Sofia

    2011-01-01

    The main purpose of the present study is to envisage the molecular mechanism of inhibitory action ofdehydrocostuslactone (DCE) andcostunolide (CS), two naturally occurring sesquiterpene lactones, towards the activation of signal transducer and activator of transcription 3 (STAT3). We report that, in human THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3 and its DNA binding activity with EC50 of 10 µM with concomitantdown-regulation ofthe phosphorylation of the tyrosine Janus kinases JAK1, JAK2 and Tyk2. Furthermore, these compounds that contain an α-β-unsatured carbonyl moiety and function as potent Michael reaction acceptor, induce a rapid drop in intracellular glutathione (GSH) concentration by direct interaction with it, thereby triggering S-glutathionylation of STAT3. Dehydrocostunolide (HCS), the reduced form of CS lacking only the α-β-unsaturated carbonyl group, fails to exert any inhibitory action. Finally, the glutathione ethylene ester (GEE), the cell permeable GSH form, reverts the inhibitory action of DCE and CS on STAT3 tyrosine phosphorylation. We conclude that these two sesquiterpene lactones are able to induce redox-dependent post-translational modification of cysteine residues of STAT3 protein in order to regulate its function. PMID:21625597

  13. Antinociceptive activity of Quillaja saponaria Mol. saponin extract, quillaic acid and derivatives in mice.

    Science.gov (United States)

    Arrau, Sylvia; Delporte, Carla; Cartagena, Carlos; Rodríguez-Díaz, Maité; González, Patricia; Silva, Ximena; Cassels, Bruce K; Miranda, Hugo F

    2011-01-07

    Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as a cleansing and analgesic agent in Chilean folk medicine. The topical and systemic analgesic effects of a commercial partially purified saponin extract, 3β,16α-dihydroxy-23-oxoolean-12-en-28-oic acid (quillaic acid), methyl 3β,16α-dihydroxy-23-oxoolean-12-en-28-oate and methyl 4-nor-3,16-dioxoolean-12-en-28-oate. The samples were assessed in mice using the topical tail-flick and i.p. hot-plate tests, respectively. All the samples showed activity in both analgesic tests in a dose-dependent manner. The most active against tail flick test was commercial partially purified saponin extract (EC50 27.9 mg%, w/v) and more than the ibuprofen sodium. On hot-plate test, methyl 4-nor-3, 16-dioxoolean-12-en-28-oate was the most active (ED50 12.2 mg/kg) and more than the ibuprofen sodium. The results of the present study demonstrated that Quillaja saponaria saponins, quillaic acid, its methyl ester, and one of the oxidized derivatives of the latter, elicit dose-dependent antinociceptive effects in two murine thermal models. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  14. Chemical analysis and calcium channel blocking activity of the essential oil of Perovskia abrotanoides.

    Science.gov (United States)

    Shah, Abdul Jabbar; Rasheed, Munawwer; Jabeen, Qaiser; Ahmed, Amir; Tareen, Rasool Bakhsh; Gilani, Anwarul Hassan; Nadir, Muhammad; Ahmad, Viqar Uddin

    2013-11-01

    The aim of this study was to investigate the chemical composition and provide a pharmacological base for the medicinal use of the essential oil of Perovskia abrotanoides (Pa.Oil) in gastrointestinal disorders, such as colic. The chemical investigation resulted in the identification of 26 compounds, of which tricyclene, beta-trans-ocimene, terpinene-4-acetate, terpinen-4-ol, caran-3beta-ol, linalyl acetate, beta-caryophyllene oxide and alpha-elemene had not previously been reported from P. abrotanoides. Major constituents were 1,8-cineol and delta-3-carene, which constituting 50% of the oil. In the isolated rabbit jejunum preparation Pa.Oil caused inhibition of spontaneous and high K+ (80 mM)-induced contractions, with respective EC50 values of 0.13 (0.08-0.20; n = 4) and 0.90 mg/mL (0.50-1.60; n = 5), thus showing that spasmolytic activity is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pre-treatment of the tissue with Pa.Oil (0.03-0.1 mg/mL) caused a rightward shift in the Ca++ concentration-response curves, similar to that caused by verapamil, a standard calcium channel blocker. These data indicate that the essential oil of P. abrotanoides possesses spasmolytic activity mediated possibly through inhibition of voltage-dependent calcium channels, which may explain its medicinal use in colic and possibly diarrhea.

  15. An appraisal of eighteen commonly consumed edible plants as functional food based on their antioxidant and starch hydrolase inhibitory activities.

    Science.gov (United States)

    Lee, Yian Hoon; Choo, Candy; Watawana, Mindani I; Jayawardena, Nilakshi; Waisundara, Viduranga Y

    2015-11-01

    Eighteen edible plants were assessed for their antioxidant potential based on oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total phenolics, vitamin C content and various lipophilic antioxidants. The inhibitory activities of the plant extracts against the enzymatic activities of α-amylase and α-glucosidase were also evaluated. The antioxidant and starch hydrolase activities of the plants varied widely across a single batch of analysis. The ORAC and DPPH radical scavenging EC50 values varied between 298 and 1984 Trolox equivalents g(-1) fresh weight and between 91 and 533 mg kg(-1) fresh weight, respectively. The total phenolics and vitamin C contents varied between 32 and 125 mg gallic acid equivalents g(-1) fresh weight and between 96 and 285 µg g(-1) fresh weight, respectively. All the plants contained neoxanthin, violaxanthin, and α- and β-carotene in varying amounts. Coccinia grandis, Asparagus racemosus, Costus speciosus, Amaranthus viridis and Annona muricata displayed the highest inhibitory activities against starch hydrolases. They were the most efficient against the breakdown of seven starches exposed to the two enzymes as well. Overall, the edible plants were observed to display a high antioxidant potential with starch hydrolase inhibitory properties, which were beneficial in their being recognized as functional food. © 2014 Society of Chemical Industry.

  16. Effect of gamma irradiation on the extraction yield, antioxidant, and antityrosinase activities of pistachio green hull extract

    Science.gov (United States)

    Abolhasani, Ali; Barzegar, Mohsen; Sahari, Mohammad Ali

    2018-03-01

    In this study, the antioxidant activity and tyrosinase inhibitory of non-irradiated and irradiated pistachio green hull (PGH) extracts were investigated. After irradiation of PGH by different doses of gamma ray (0, 10, 20, 30 and 40 kGy), their phenolic compounds were extracted by water. Antioxidant activities of extracts were examined by DPPH• and FRAP methods. The results showed that irradiation not only do not have negative effects on antioxidant activity but also it can increase the amount of total phenolic compounds of water extract in comparison with non-irradiated sample. Water extract of irradiated PGH at the dose of 30 kGy, showed the highest antioxidant activity in the DPPH° test with EC50 equal to 289.0 ± 1.2 μg/ml. Irradiated (30 kGy) and non-irradiated water extracts had the highest antityrosinase activities with IC50 of 10.8 ± 1.1 and 11.9 ± 1.2 μg phenolic/ml, respectively. In addition, it was found that the water extract of irradiated PGH can prevent enzymatic browning in sliced raw potatoes. According to the antityrosinase potential of PGH extract, it may be suggested as an antibrowning agent in some foodstuffs or cosmetic products.

  17. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity

    International Nuclear Information System (INIS)

    Axon, Andrew; May, Felicity E.B.; Gaughan, Luke E.; Williams, Faith M.; Blain, Peter G.; Wright, Matthew C.

    2012-01-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings – sunset yellow and tartrazine – were identified as novel human ERα activators, activating the human ER with an EC 50% concentration of 220 and 160 nM, respectively.

  18. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity.

    Science.gov (United States)

    Axon, Andrew; May, Felicity E B; Gaughan, Luke E; Williams, Faith M; Blain, Peter G; Wright, Matthew C

    2012-08-16

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Chemical composition and antioxidant activity of berry fruits

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    Stajčić Slađana M.

    2012-01-01

    Full Text Available The main chemical composition, contents of total phenolic (TPh, total flavonoid (TF, and total monomeric anthocyianin (TMA, as well as the antioxidant activity of two raspberry cultivars (Meeker and Willamette, two blackberry cultivars (Čačanska bestrna and Thornfree and wild bilberry were studied. The raspberry cultivars had the highest total solids among fruits investigated. Bilberry fruits had the highest sugar-to-acid ratio. Blackberry fruits were richer in crude fibers (cellulose in comparison to raspberry and bilberry fruits. The content of pectic substances was highest in the bilberry. Also, bilberry had a highest content of TPh (808.12 mg GAE/100 g FW, TF (716.31 mg RE/100 g FW and TMA (447.83 mg CGE/100 g FW. The antioxidant activity was evaluated spectrophotometrically, using 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging activity assay. The DPPH free radical scavenging activity, expressed as the EC50 value (in mg of fresh weight of berry fruit per ml of the reaction mixture, of bilberry (0.3157 ± 0.0145 mg/ml was the highest. These results also showed that the antioxidant value of 100 g FW bilberry, raspberry - Willamette, raspberry - Meeker, blackberry - Čačanska bestrna and blackberry - Thornfree is equivalent to 576.50 mg, 282.74 mg, 191.58 mg, 222.28 mg and 272.01 mg of vitamin C, respectively. There was a significant positive correlation between the antioxidant activities and content of total phenolics (RTPh 2=0.9627, flavonoids (RTF 2=0.9598 and anthocyanins (RTMA 2=0.9496 in berry fruits. [Projekat Ministarstva nauke Republike Srbije, br. TR 31044

  20. Phenolic Composition and Antioxidant and Antiproliferative Activities of the Extracts of Twelve Common Bean (Phaseolus vulgaris L.) Endemic Ecotypes of Southern Italy before and after Cooking

    Science.gov (United States)

    Ombra, Maria Neve; d'Acierno, Antonio; Riccardi, Riccardo; Spigno, Patrizia; Zaccardelli, Massimo; Pane, Catello; Maione, Mena; Fratianni, Florinda

    2016-01-01

    Beans are important dietary components with versatile health benefits. We analysed the extracts of twelve ecotypes of Phaseolus vulgaris in order to determine their phenolic profiles, antioxidant activity, and the in vitro antiproliferative activity. Ultra-performance liquid chromatography with diode array detector (UPLC-DAD) admitted us to detect and quantify some known polyphenols, such as gallic acid, chlorogenic acid, epicatechin, myricetin, formononetin, caffeic acid, and kaempferol. The antioxidant activity (AA) ranged from 1.568 ± 0.041 to 66.572 ± 3.197 mg necessary to inhibit the activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by 50% (EC50). The extracts, except those obtained from the nonpigmented samples, were capable of inhibiting the proliferation of the human epithelial colorectal adenocarcinoma (Caco-2) cells, human breast cancer cells MCF-7, and A549 NSCLC cell line. Cultivars differed in composition and concentration of polyphenols including anthocyanins; cooking affected the antioxidant activity only marginally. Qualitative and quantitative differences in phenolic composition between the groups of beans influenced the biological activities; on the other hand, we did not find significant differences on the biological activities within the same variety, before and after cooking. PMID:28105248

  1. Effect of steeping temperature on antioxidant and inhibitory activities of green tea extracts against α-amylase, α-glucosidase and intestinal glucose uptake.

    Science.gov (United States)

    Liu, Shuyuan; Ai, Zeyi; Qu, Fengfeng; Chen, Yuqiong; Ni, Dejiang

    2017-11-01

    The objective of the present study was to evaluate the effect of steeping temperature on the biological activities of green tea, including the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, α-glucosidase and α-amylase inhibitory activities, and glucose uptake inhibitory activity in Caco-2 cells. Results showed that, with increasing extraction temperature, the polyphenol content increased, which contributed to enhance antioxidant activity and inhibitory effects on α-glucosidase and α-amylase. Green tea steeped at 100°C showed the highest DPPH radical-scavenging activity and inhibitory effects on α-glucosidase and α-amylase activities with EC 50 or IC 50 values of 6.15μg/mL, 0.09mg/mL, and 6.31mg/mL, respectively. However, the inhibitory potential on glucose uptake did not show an upward trend with increasing extraction temperature. Green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (ptea. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Inhibition of the DNA polymerase and RNase H activities of HIV-1 reverse transcriptase and HIV-1 replication by Brasenia schreberi (Junsai) and Petasites japonicus (Fuki) components.

    Science.gov (United States)

    Hisayoshi, Tetsuro; Shinomura, Mayu; Yokokawa, Kanta; Kuze, Ikumi; Konishi, Atsushi; Kawaji, Kumi; Kodama, Eiichi N; Hata, Keishi; Takahashi, Saori; Nirasawa, Satoru; Sakuda, Shohei; Yasukawa, Kiyoshi

    2015-07-01

    Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) possesses two distinct enzymatic activities: those of RNA- and DNA-dependent DNA polymerases and RNase H. In the current HIV-1 therapy, all HIV-1 RT inhibitors inhibit the activity of DNA polymerase, but not that of RNase H. We previously reported that ethanol and water extracts of Brasenia schreberi (Junsai) inhibited the DNA polymerase activity of HIV-1 RT [Hisayoshi et al. (2014) J Biol Macromol 14:59-65]. In this study, we screened 43 edible plants and found that ethanol and water extracts of Brasenia schreberi and water extract of Petasites japonicus strongly inhibit not only the activity of DNA polymerase to incorporate dTTP into poly(rA)-p(dT)15 but also the activity of RNase H to hydrolyze the RNA strand of an RNA/DNA hybrid. In addition, these three extracts inhibit HIV-1 replication in human cells, with EC50 values of 1-2 µg/ml. These results suggest that Brasenia schreberi and Petasites japonicus contain substances that block HIV-1 replication by inhibiting the DNA polymerase activity and/or RNase H activity of HIV-1 RT.

  3. Influence of Amino Acid Compositions and Peptide Profiles on Antioxidant Capacities of Two Protein Hydrolysates from Skipjack Tuna (Katsuwonus pelamis Dark Muscle

    Directory of Open Access Journals (Sweden)

    Chang-Feng Chi

    2015-04-01

    Full Text Available Influence of amino acid compositions and peptide profiles on antioxidant capacities of two protein hydrolysates from skipjack tuna (Katsuwonus pelamis dark muscle was investigated. Dark muscles from skipjack tuna were hydrolyzed using five separate proteases, including pepsin, trypsin, Neutrase, papain and Alcalase. Two hydrolysates, ATH and NTH, prepared using Alcalase and Neutrase, respectively, showed the strongest antioxidant capacities and were further fractionated using ultrafiltration and gel filtration chromatography. Two fractions, Fr.A3 and Fr.B2, isolated from ATH and NTH, respectively, showed strong radical scavenging activities toward 2,2-diphenyl-1-picrylhydrazyl radicals (EC50 1.08% ± 0.08% and 0.98% ± 0.07%, hydroxyl radicals (EC50 0.22% ± 0.03% and 0.48% ± 0.05%, and superoxide anion radicals (EC50 1.31% ± 0.11% and 1.56% ± 1.03% and effectively inhibited lipid peroxidation. Eighteen peptides from Fr.A3 and 13 peptides from Fr.B2 were isolated by reversed-phase high performance liquid chromatography, and their amino acid sequences were determined. The elevated antioxidant activity of Fr.A3 might be due to its high content of hydrophobic and aromatic amino acid residues (181.1 and 469.9 residues/1000 residues, respectively, small molecular sizes (3–6 peptides, low molecular weights (524.78 kDa, and amino acid sequences (antioxidant score 6.11. This study confirmed that a smaller molecular size, the presence of hydrophobic and aromatic amino acid residues, and the amino acid sequences were the key factors that determined the antioxidant activities of the proteins, hydrolysates and peptides. The results also demonstrated that the derived hydrolysates and fractions from skipjack tuna (K. pelamis dark muscles could prevent oxidative reactions and might be useful for food preservation and medicinal purposes.

  4. Two new compounds and anti-HIV active constituents from Illicium verum.

    Science.gov (United States)

    Song, Wen-Yong; Ma, Yun-Bao; Bai, Xue; Zhang, Xue-Mei; Gu, Qiong; Zheng, Yong-Tang; Zhou, Jun; Chen, Ji-Jun

    2007-04-01

    Two new compounds named illiverin A (1) and tashironin A (8) were isolated from the roots of Illicium verum, together with seven known compounds: 4-allyl-2-(3-methylbut-2-enyl)-1,6-methylenedioxybenzene-3-ol (2), illicinole (3), 3-hydroxy-4,5-methylenedioxyallyl-benzene (4), (-)-illicinone-A (5), 4-allyl-4-(3-methylbut-2-enyl)-1,2-methylenedioxycyclohexa-2,6-dien-5-one (6), 3,4-seco-(24 Z)- cycloart-4(28),24-diene-3,26-dioic acid, 26-methyl ester (7) and tashironin (9). Based on 1D- and 2D-NMR data (COSY, HMQC, HMBC), the structures of the new compounds were deduced to be (E)-1-[(3-methylbut-2-enyl)oxy]-2-methoxy-4-(prop-1-enyl)benzene (1) and 11-O-debenzoyl-11alpha-O-2-methylcyclopent-1-enecarboxyltashironin (8). Compounds 1-9 were screened for anti-HIV activity in vitro whereby compounds 5 and 7 possessed moderate anti-HIV activity with EC50 values of 16.0 and 5.1 microM with SI values of 18.2 and 15.6, respectively.

  5. Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L.

    Science.gov (United States)

    Dos Santos, Ana C; Baggio, Cristiane H; Freitas, Cristina S; Lepieszynski, Juliana; Mayer, Bárbara; Twardowschy, André; Missau, Fabiana C; dos Santos, Elide P; Pizzolatti, Moacir G; Marques, Maria C A

    2008-06-01

    Arctium lappa L. is used in folk medicine as a diuretic, depurative and digestive stimulant and in dermatological conditions. The objective of this study was to evaluate the effect and the possible mechanisms involved in the gastroprotective effects of a chloroform extract (CE) of the roots from A. lappa and its fractions. Oral pretreatment with CE (10, 30 and 100 mg kg(-1)) significantly reduced gastric lesions induced by ethanol by 61%, 70% and 76%, respectively. Oral administration of CE (100 mg kg(-1) per day for 7 days) reduced the chronic gastric ulceration induced by acetic acid by 52%. Intraduodenal CE (100, 300 and 600 mg kg(-1)) reduced the total acidity of gastric secretion by 22%, 22% and 33%, respectively, while i.p. administration (10, 30 and 100 mg kg(-1)) inhibited total acidity by 50%, 60% and 67%, respectively. In-vitro, CE inhibited H+, K+ -ATPase activity with an EC50 of 53 microgmL(-1) and fraction A (30 and 100 microgmL(-1)) reduced this by 48% and 89%, respectively. CE had no effect on gastrointestinal motility. CE (250 microgmL(-1)) and fraction B (100 and 250 microgmL(-1)) had free-radical scavenging ability, inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical activity by 50%, 20% and 55%, respectively. Collectively, the results show that the CE protects animals from gastric lesions by reducing gastric acid secretion via inhibition of gastric H+, K+ -ATPase.

  6. Antiviral Activity of Fridericia formosa (Bureau L. G. Lohmann (Bignoniaceae Extracts and Constituents

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    Geraldo Célio Brandão

    2017-01-01

    Full Text Available A phytochemical study of Fridericia formosa (Bignoniaceae ethanol extracts of leaves, stems, and fruits was guided by in vitro assays against vaccinia virus Western Reserve (VACV-WR, human herpes virus 1 (HSV-1, murine encephalomyocarditis virus (EMCV, and dengue virus type 2 (DENV-2 by the MTT method. All the ethanol extracts were active against DENV-2, HSV-1, and VACV-WR with best results for the fruits extract against DENV-2 (SI > 38.2. For VACV-WR and HSV-1, EC50 values > 200 μg mL−1 were determined, while no inhibition of the cytopathic effect was observed with EMCV. Five compounds were isolated and identified as the C-glucosylxanthones mangiferin (1, 2′-O-trans-caffeoylmangiferin (2, 2′-O-trans-coumaroylmangiferin (3, 2′-O-trans-cinnamoylmangiferin (5, and the flavonoid chrysin (4. The most active compound was 2′-O-trans-coumaroylmangiferin (3 with SI > 121.9 against DENV-2 and 108.7 for HSV-1. These results indicate that mangiferin cinnamoyl esters might be potential antiviral drugs.

  7. Vascular smooth muscle contraction induced by Na+ channel activators, veratridine and batrachotoxin.

    Science.gov (United States)

    Shinjoh, M; Nakaki, T; Otsuka, Y; Sasakawa, N; Kato, R

    1991-11-26

    The effects of the sodium channel activators veratridine and batrachotoxin on isolated rat aorta were investigated. Veratridine caused gradual contraction, independent of the presence of endothelium, with an EC50 of 35 microM. Batrachotoxin (1 microM) also induced contraction. Both effects were completely inhibited by the sodium channel blocker tetrodotoxin (1 microM). The veratridine (60 microM)-induced contraction was inhibited by nifedipine (0.1 microM). In the absence of extracellular Ca2+, veratridine (60 microM) did not cause contraction. Sodium nitroprusside (80 nM), acetylcholine (10 microM) and isoproterenol (1 microM) caused relaxation of rings precontracted with veratridine (60 microM). An inhibitor of endothelium-derived relaxing factor (EDRF) synthase, N omega-nitro-L-arginine methyl ester (L-NAME) (0.65 mM), enhanced the veratridine-induced contraction in rings with an intact endothelium, which suggests that EDRF was being released during the veratridine-induced contraction. These results show that the activation of sodium channels on smooth muscle cells induces a contraction that is probably mediated by Ca2+ influx through voltage-dependent Ca2+ channels.

  8. Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons

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    Zhengyu Cao

    2015-02-01

    Full Text Available The frequent occurrence of Moorea producens (formerly Lyngbya majuscula blooms has been associated with adverse effects on human health. Hoiamide A is a structurally unique cyclic depsipeptide isolated from an assemblage of the marine cyanobacteria M. producens and Phormidium gracile. We examined the influence of hoiamide A on neurite outgrowth in neocortical neurons and found that it suppressed neurite outgrowth with an IC50 value of 4.89 nM. Further study demonstrated that hoiamide A stimulated lactic acid dehydrogenase (LDH efflux, nuclear condensation and caspase-3 activity with EC50 values of 3.66, 2.55 and 4.33 nM, respectively. These data indicated that hoiamide A triggered a unique neuronal death profile that involves both necrotic and apoptotic mechanisms. The similar potencies and similar time-response relationships between LDH efflux and caspase-3 activation/nuclear condensation suggested that both necrosis and apoptosis may derive from interaction with a common molecular target. The broad-spectrum caspase inhibitor, Z-VAD-FMK completely inhibited hoiamide A-induced neurotoxicity. Additionally, hoiamide A stimulated JNK phosphorylation, and a JNK inhibitor attenuated hoiamide A-induced neurotoxicity. Collectively, these data demonstrate that hoiamide A-induced neuronal death requires both JNK and caspase signaling pathways. The potent neurotoxicity and unique neuronal cell death profile of hoiamide A represents a novel neurotoxic chemotype from marine cyanobacteria.

  9. Synthesis and antiviral activity of 8-aza analogs of chiral [2-(phosphonomethoxy) propyl]guanines.

    Science.gov (United States)

    Franchetti, P; Sheikha, G A; Cappellacci, L; Grifantini, M; De Montis, A; Piras, G; Loi, A G; La Colla, P

    1995-09-29

    (R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.

  10. Purification, characterization and biological activities of a polysaccharide from Lepidium meyenii leaves.

    Science.gov (United States)

    Li, Shufang; Hao, Limin; Kang, Qiaozhen; Cui, Yinxin; Jiang, Hui; Liu, Xin; Lu, Jike

    2017-10-01

    The characteristics and biological activities of a novel polysaccharide from Lepidium meyenii leaves (LMLP) were investigated. LMLP was purified using DEAE-52 cellulose chromatography followed by SephadexG-100 chromatography. The average molecule weight of LMLP was 58.43kDa and it was composed of galactose, arabinose, rhamnose, glucose and mannose with a relative molar ratio of 5.51:4.05:1.15:0.77:0.01. Antioxidant activity results showed that LMLP presented an EC 50 of 3.72mg/mL in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, and it also had reducing power (OD700nm being 0.079 at 1mg/mL). Moreover, LMLP possessed the potential on stimulating immune response of RAW264.7 cells. It could promote proliferation, strengthen phagocytosis function, enhance the expression of CD80, and increase the secretion of nitric oxide (NO) in a dose-dependent manner. All of these results suggested that LMLP could be used as a natural ingredient for functional food. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids.

    Science.gov (United States)

    Dobričić, Vladimir; Jaćević, Vesna; Vučićević, Jelica; Nikolic, Katarina; Vladimirov, Sote; Čudina, Olivera

    2017-05-01

    Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17β-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC 50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Metabolic activities of five botryticides against Botrytis cinerea examined using the Biolog FF MicroPlate.

    Science.gov (United States)

    Wang, Hancheng; Wang, Jin; Li, Licui; Hsiang, Tom; Wang, Maosheng; Shang, Shenghua; Yu, Zhihe

    2016-08-05

    Tobacco grey mold caused by Botrytis cinerea is an important fungal disease worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are representative botryticides for grey mold management. This research investigated the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog FF Microplate. All five chemicals showed inhibitory activity, with average EC50 values of 0.94, 0.05, 0.50, 0.61 and 0.31 μg ml(-1), respectively. B. cinerea metabolized 96.8% of tested carbon sources, including 29 effectively and 33 moderately, but the metabolic fingerprints differed under pressures imposed by these botryticides. For boscalid, B. cinerea was unable to metabolize many substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources related to glycolysis were not metabolized. For iprodione, use of most carbon substrates was weakly inhibited, and the metabolic profile was similar to that of the control. For propiconazole, no carbon substrates were metabolized and the physiological and biochemical functions of the pathogen were totally inhibited. These findings provide useful information on metabolic activities of these botryticides, and may lead to future applications of the Biolog FF Microplate for examining metabolic effects of other fungicides on other fungi, as well as providing a metabolic fingerprint of B. cinerea that could be useful for identification.

  13. Isolation, purification and antioxidant activity of polysaccharides from the leaves of maca (Lepidium Meyenii).

    Science.gov (United States)

    Caicai, Kang; Limin, Hao; Liming, Zhang; Zhiqiang, Zheng; Yongwu, Yang

    2018-02-01

    Two fractions of polysaccharides (MLP-1 and MLP-2) were extracted from the leaves of maca (Lepidium Meyenii Walp.) by water, and purified using DEAE-52 ion exchange resin and sephadex G-200 clumns chromatography. An investigation was carried out for their structural characterization and antioxidant activity in vitro. The results indicated that MLP-1 was mainly composed of ribose, rhamnose, arabinose, xylose, mannose, glucose and galactose, with the molar ratio of 0.12:0.32:1.50:0.32:1.03:1.00:0.93; the MLP-2 was a homopolysaccharide composed of glucose. The molecular weight (Mw) of MLP-1 was 42756Da, and the Mw of MLP-2 was 93541Da. The FT-IR spectra showed the general characteristic absorption peak of maca leaf polysaccharides (MLPs). The evaluation of antioxidant activity revealed that MLP-1 had strong scavenging effects in vitro on hydroxyl, superoxide anion and DPPH radicals, whose EC 50 (mg/mL) was 0.44, 0.21, and 0.82, respectively. Both MLP-1 and MLP-2 presented dose-dependently positive effects on the antioxidant-related parameters. The results suggested that the purified MLP-1 displayed better antioxidant capacities than that of MLP-1, which could be explored as potential antioxidant agents for the complementary medicine or functional foods. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Spirocyclic chromanes exhibit antiplasmodial activities and inhibit all intraerythrocytic life cycle stages.

    Science.gov (United States)

    Roberts, Bracken F; Iyamu, Iredia D; Lee, Sukjun; Lee, Eunyoung; Ayong, Lawrence; Kyle, Dennis E; Yuan, Yu; Manetsch, Roman; Chakrabarti, Debopam

    2016-04-01

    We screened a collection of synthetic compounds consisting of natural-product-like substructural motifs to identify a spirocyclic chromane as a novel antiplasmodial pharmacophore using an unbiased cell-based assay. The most active spirocyclic compound UCF 201 exhibits a 50% effective concentration (EC50) of 350 nM against the chloroquine-resistant Dd2 strain and a selectivity over 50 using human liver HepG2 cells. Our analyses of physicochemical properties of UCF 201 showed that it is in compliance with Lipinski's parameters and has an acceptable physicochemical profile. We have performed a limited structure-activity-relationship study with commercially available chromanes preserving the spirocyclic motif. Our evaluation of stage specificities of UCF 201 indicated that the compound is early-acting in blocking parasite development at ring, trophozoite and schizont stages of development as well as merozoite invasion. SPC is an attractive lead candidate scaffold because of its ability to act on all stages of parasite's aexual life cycle unlike current antimalarials.

  15. Chemical structure and antioxidant activity of a new exopolysaccharide produced from Micrococcus luteus

    Directory of Open Access Journals (Sweden)

    Mohsen Mohamed Selim Asker

    2014-12-01

    Full Text Available An exopolysaccharide (EPS reaching a maximum of 13 g/L was isolated from Micrococcus luteus by ethanol precipitation. The crude EPS was purified by chromatography on DEAE-cellulose and Sephacryl S-200, affording a polysaccharide active fraction (AEP with a molecular weight of ∼137 kDa. AEP was investigated by a combination of chemical and chromatographic methods including FTIR, HPLC, periodate oxidation, methylation and GC–MS. Data obtained indicated that AEP was composed of mannose, arabinose, glucose and glucuronic acid in a molar ratio of 3.6:2.7:2.1:1.0, respectively. The main backbone consists of mannose units linked with (1→6-glycosidic bonds and arabinose units linked with (1→5-glycosidic bonds. There is a side chain consisting of mannose units linked with (1→6-glycosidic bonds at C3, when all glucose and most of glucuronic acid are found in the side chain. The in vitro antioxidant assay showed that AEP possesses DPPH radical-scavenging activity, with an EC50 value of 180 μg/mL.

  16. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database.

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P S; Agarwal, Subhash M

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC(50)/ED(50)/EC(50)/GI(50)), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients' Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI(50) data.

  17. Antioxidant, Anti-Nephrolithe Activities and in Vitro Digestibility Studies of Three Different Cyanobacterial Pigment Extracts.

    Science.gov (United States)

    Paliwal, Chetan; Ghosh, Tonmoy; Bhayani, Khushbu; Maurya, Rahulkumar; Mishra, Sandhya

    2015-08-20

    Phycobiliprotein-containing water and carotenoid-containing methanolic extracts of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti-nephrolithe activities. The best EC50 values for DPPH scavenging were in Lyngbya water (LW, 18.78 ± 1.57 mg·mg(-1) DPPH) and Lyngbya methanol (LM, 59.56 ± 37.38 mg·mg(-1) DPPH) extracts. Iso-bolographic analysis revealed most of the combinations of extracts were antagonistic to each other, although LM-Spirulina methanol (SM) 1:1 had the highest synergistic rate of 86.65%. In vitro digestion studies showed that DPPH scavenging activity was considerably decreased in all extracts except for Pseudanabaena methanol (PM) and LM after the simulated digestion. All of the extracts were effective in reducing the calcium oxalate crystal size by nearly 60%-65% compared to negative control, while PM and Spirulina water (SW) extracts could inhibit both nucleation and aggregation of calcium oxalate by nearly 60%-80%.

  18. Antioxidant, Anti-Nephrolithe Activities and in Vitro Digestibility Studies of Three Different Cyanobacterial Pigment Extracts

    Directory of Open Access Journals (Sweden)

    Chetan Paliwal

    2015-08-01

    Full Text Available Phycobiliprotein-containing water and carotenoid-containing methanolic extracts of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti-nephrolithe activities. The best EC50 values for DPPH scavenging were in Lyngbya water (LW, 18.78 ± 1.57 mg·mg−1 DPPH and Lyngbya methanol (LM, 59.56 ± 37.38 mg·mg−1 DPPH extracts. Iso-bolographic analysis revealed most of the combinations of extracts were antagonistic to each other, although LM—Spirulina methanol (SM 1:1 had the highest synergistic rate of 86.65%. In vitro digestion studies showed that DPPH scavenging activity was considerably decreased in all extracts except for Pseudanabaena methanol (PM and LM after the simulated digestion. All of the extracts were effective in reducing the calcium oxalate crystal size by nearly 60%–65% compared to negative control, while PM and Spirulina water (SW extracts could inhibit both nucleation and aggregation of calcium oxalate by nearly 60%–80%.

  19. Bioavailability of antibiotics at soil-water interfaces - A comparison of measured activities and equilibrium partitioning (EqP) estimates.

    Science.gov (United States)

    Menz, Jakob; Müller, Julia; Olsson, Oliver; Kümmerer, Klaus

    2018-04-09

    There are growing concerns that antibiotic pollution impacts environmental microbiota and facilitates the propagation of antibiotic resistance. However, the prediction or analytical determination of bioavailable concentrations of antibiotics in soil is still subject to great uncertainty. Biological assays are increasingly recognized as valuable complementary tools that allow a more direct determination of the residual antibiotic activity. This study assessed the bioavailability of structurally diverse antibiotics at a soil-water interface applying activity-based analyses in conjunction with equilibrium partitioning (EqP) modelling. The activity against gram-positive and gram-negative bacteria of nine antibiotics from different classes was determined in the presence and absence of standard soil (LUFA St. 2.2). The addition of soil affected the activity of different antibiotics to highly varying degrees. Moreover, a highly significant correlation (p<0.0001) between the experimentally observed and the EqP-derived log EC 50 values was observed. The innovative experimental design of this study provided new insights on the bioavailability of antibiotics at soil-water interfaces. EqP appears to be applicable to a broad range of antibiotics for the purpose of screening-level risk assessment. However, EqP estimates cannot replace soil-specific ecotoxicity testing in higher-tier assessments, since their accuracy is still compromised by a number of factors.

  20. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells.

    Science.gov (United States)

    Liao, Wenzhen; Chen, Luying; Ma, Xiang; Jiao, Rui; Li, Xiaofeng; Wang, Yong

    2016-05-23

    The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Antiviral activities of plants occurring in the state of Minas Gerais, Brazil: Part 2. Screening Bignoniaceae species

    Directory of Open Access Journals (Sweden)

    Geraldo Célio Brandão

    2010-11-01

    Full Text Available Ethanol extracts of eighteen Bignoniaceae species have been evaluated by the MTT assay for cytotoxicity in Vero cells and for antiviral activity against Human herpes virus type 1, Vaccinia virus and murine Encephalomyocarditis virus. Among such species, seven are reported to be of traditional medicinal use No cytotoxicity was observed for most of the extracts up to the concentration of 500 μg/mL. Fourteen (50% of the 28 extracts assayed have disclosed antiviral activity with EC50 values in the range of 4.6+0.3 to 377.2+17.7 μg/mL. Only two species, Arrabidaea samydoides and Callichlamys latifolia, have shown activity against all the three viruses. The extracts were chemically characterized by their TLC and HPLC-DAD profiles. Mangiferin is the major constituent of A. samydoides but the isolated compound has been less active than the crude extract. This is the first report on the antiviral evaluation of the eighteen Bignoniaceae species assayed.

  2. In vitro antiviral characteristics of HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068.

    Science.gov (United States)

    Nowicka-Sans, Beata; Gong, Yi-Fei; McAuliffe, Brian; Dicker, Ira; Ho, Hsu-Tso; Zhou, Nannan; Eggers, Betsy; Lin, Pin-Fang; Ray, Neelanjana; Wind-Rotolo, Megan; Zhu, Li; Majumdar, Antara; Stock, David; Lataillade, Max; Hanna, George J; Matiskella, John D; Ueda, Yasutsugu; Wang, Tao; Kadow, John F; Meanwell, Nicholas A; Krystal, Mark

    2012-07-01

    BMS-663068 is the phosphonooxymethyl prodrug of BMS-626529, a novel small-molecule attachment inhibitor that targets HIV-1 gp120 and prevents its binding to CD4(+) T cells. The activity of BMS-626529 is virus dependent, due to heterogeneity within gp120. In order to better understand the anti-HIV-1 spectrum of BMS-626529 against HIV-1, in vitro activities against a wide variety of laboratory strains and clinical isolates were determined. BMS-626529 had half-maximal effective concentration (EC(50)) values of 6 log(10), with half-maximal effective concentration values in the low pM range against the most susceptible viruses. The in vitro antiviral activity of BMS-626529 was generally not associated with either tropism or subtype, with few exceptions. Measurement of the binding affinity of BMS-626529 for purified gp120 suggests that a contributory factor to its inhibitory potency may be a relatively long dissociative half-life. Finally, in two-drug combination studies, BMS-626529 demonstrated additive or synergistic interactions with antiretroviral drugs of different mechanistic classes. These results suggest that BMS-626529 should be active against the majority of HIV-1 viruses and support the continued clinical development of the compound.

  3. Nanomolar cellular antisense activity of peptide nucleic acid (PNA) cholic acid ("umbrella") and cholesterol conjugates delivered by cationic lipids.

    Science.gov (United States)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-02-15

    Limited cellular uptake and low bioavailability of peptide nucleic acids (PNAs) have restricted widespread use of PNAs as antisense/antigene agents for cells in culture and not least for in vivo applications. We now report the synthesis and cellular antisense activity in cultured HeLa pLuc705 cells of cholesterol and cholic acid ("umbrella") derivatives of splice correction antisense PNA oligomers. While the conjugates alone were practically inactive up to 1 μM, their activity was dramatically improved when delivered by a cationic lipid transfection agent (LipofectAMINE2000). In particular, PNAs, conjugated to cholesterol through an ester hemisuccinate linker or to cholic acid, exhibited low nanomolar activity (EC(50) ∼ 25 nM). Excellent sequence specificity was retained, as mismatch PNA conjugates did not show any significant antisense activity. Furthermore, we show that increasing the transfection volume improved transfection efficiency, suggesting that accumulation (condensation) of the PNA/lipid complex on the cellular surface is part of the uptake mechanism. These results provide a novel, simple method for very efficient cellular delivery of PNA oligomers, especially using PNA-cholic acid conjugates which, in contrast to PNA-cholesterol conjugates, exhibit sufficient water solubility. The results also question the generality of using cholic acid "umbrella" derivatives as a delivery modality for antisense oligomers.

  4. Chemical Composition, Cytotoxic and Antimicrobial Activity of Essential Oils from Cassia bakeriana Craib. against Aerobic and Anaerobic Oral Pathogens

    Directory of Open Access Journals (Sweden)

    Cláudio V. da Silva

    2013-04-01

    Full Text Available The chemical composition of the essential oils from leaves, bark and wood of Cassia bakeriana Craib. was determined by gas chromatography (GC and gas chromatography–mass spectrometry (GC-MS. Alcohols, aldehydes and fatty acids were the major components in leaf and bark oil, while wood essential oil was rich in fatty acids. Terpenes such as linalool, (E-nerolidol and phytol were present in low concentrations. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated using the microdilution method, as was the cell viability test carried out with Vero cells. The oils from leaves and bark showed high antimicrobial activity, with minimum inhibitory concentrations between 62.5 and 125 µg·mL−1 for most of the tested bacteria, including Streptococcus mutans, the main etiological agent of dental caries. Leaves oil displayed the lowest cytotoxic effect (EC50 of 153 µg·mL−1, while wood oil exhibited the highest toxicity to Vero cells. C. bakeriana oils are thus a source of biologically active compounds against aerobic and anaerobic oral microorganisms. This study is the first report on the chemical composition, antimicrobial activity and cytotoxicity of C. bakeriana.

  5. Serotonin has kinin-like activity in stimulating secretion by Malpighian tubules of the house cricket Acheta domesticus.

    Science.gov (United States)

    Coast, Geoffrey

    2011-03-01

    Serotonin stimulates secretion by Malpighian tubules (MT) of a number of insects, and functions as a diuretic hormone in Rhodnius prolixus and in larval Aedes aegypti. Serotonin is here shown to be a potent stimulant of secretion by MT of the house cricket, Acheta domesticus, with an apparent EC(50) of 9.4 nmol L(-1), although its diuretic activity is just 25% of the maximum achievable with either the native CRF-related peptide, Achdo-DH, or a crude extract of the corpora cardiaca. In this respect, the diuretic activity of serotonin is similar to that of the cricket kinin Achdo-KI, and when tested together their actions are not additive, which suggests they target the same transport process. Consistent with this suggestion, the activity of serotonin is chloride-dependent and is associated with a non-selective stimulation of NaCl and KCl transport. In common with Achdo-KI, serotonin has no effect on cAMP production by isolated MT, and both act synergistically with exogenous 8bromo-cAMP in stimulating fluid secretion, most likely by promoting the release of Ca(2+) from intracellular stores. A number of serotonin agonists and antagonists were tested to determine the pharmacological profile of receptors on cricket MT. The results are consistent with the diuretic activity of serotonin being mediated through a 5-HT(2)-like receptor. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Evaluation of antioxidant activity and identification of main compounds of various extracts of Artemisia turanica aerial parts

    Directory of Open Access Journals (Sweden)

    M. Mojarrab*

    2017-11-01

    Full Text Available Background and objectives: Artemisia turanica Krash. grows wildly in north-eastern Iran. The aim of the present work was to undertake an investigation of the antioxidant activity as well as identification of main compound of different extracts and fractions of A. turanica. Methods: Total phenolic contents (TPC and antioxidant activity of five different extracts (petroleum ether, dichloromethane, ethyl acetate, ethanol and ethanol-water and seven fraction of hydroethanolic extract was investigated by Folin-Ciocalteu assay and three different methods: β-catotene bleaching (BCB test, 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging method and ferrous ion chelating (FIC assays, respectively. Purification of the major constituents of the most active fraction was done by preparative and semi preparative HPLC. Structure elucidation of isolated compounds was achieved using spectroscopic techniques including ESIMS, 1D and 2D NMR experiments. Results: Among the extracts analyzed, the hydroethanolic extract exhibited the highest phenolic content. Fraction D (40% MeOH in water showed the highest total phenolics content and free radical scavenging activity but the only statistically significant correlation between TPC and EC50 values was observed for BCB. There were no significant differences (p

  7. PHYTOCHEMICAL ANALYSIS, ANTIOXIDANT AND ...

    African Journals Online (AJOL)

    2012-12-31

    EC50 in μg/ml) and total antioxidant activity (mg GAE/g DW) power Phoenyx dactylifera leaves extract and anthentic standards (BHT in IC50, BHA and chlorogenic acid in EC50 μg/ml). Plant species and standards. DPPH test.

  8. [In vitro evaluation of antileishmania activity of Artemisia herba alba Asso].

    Science.gov (United States)

    Hatimi, S; Boudouma, M; Bichichi, M; Chaib, N; Idrissi, N G

    2001-03-01

    Aqueous extract and essential oil of Artemisia herba-alba Asso were tested for their antileshmanial activity again Leishmania tropica and Leishmania major. The strongest leishmanicidal activity was observed with the essential oil at 2 micrograms/ml as versus the other two strains tested. The aqueous extract showed an antileshmanial activity at 4 micrograms/ml.

  9. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay.

    Science.gov (United States)

    Hassan, Sherif T S; Švajdlenka, Emil; Berchová-Bímová, Kateřina

    2017-04-30

    For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC 50 values of 0.92 and 1.43 µg∙mL -1 , respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC 50 value of 82.4 µg∙mL -1 . This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  10. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay

    Directory of Open Access Journals (Sweden)

    Sherif T. S. Hassan

    2017-04-01

    Full Text Available For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS and its bioactive constituent protocatechuic acid (PCA, have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL−1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL−1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  11. Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety

    Directory of Open Access Journals (Sweden)

    Lu Yu

    2017-04-01

    Full Text Available 1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, 1H-NMR, and 13C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV and cucumber mosaic virus (CMV in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38, 297.40, 248.18, and 129.87 μg/mL, respectively, which were superior to that of ribavirin (457.25 µg/mL. In addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic ring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering new antiviral agents.

  12. Nuclear Factor Kappa B Activation and Peroxisome Proliferator-activated Receptor Transactivational Effects of Chemical Components of the Roots of Polygonum multiflorum.

    Science.gov (United States)

    Sun, Ya Nan; Li, Wei; Song, Seok Bean; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

    2016-01-01

    Polygonum multiflorum is well-known as "Heshouwu" in traditional Chinese herbal medicine. In Northeast Asia, it is often used as a tonic to prevent premature aging of the kidney and liver, tendons, and bones and strengthening of the lower back and knees. To research the anti-inflammatory activities of components from P. multiflorum. The compounds were isolated by a combination of silica gel and YMC R-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-nuclear magnetic resonance, and mass spectrometry). The anti-inflammatory activities of the isolated compounds 1-15 were evaluated by luciferase reporter gene assays. Fifteen compounds (1-15) were isolated from the roots of P. multiflorum. Compounds 1-5 and 14-15 significantly inhibited tumor necrosis factor-α-induced nuclear factor kappa B-luciferase activity, with IC50 values of 24.16-37.56 μM. Compounds 1-5 also greatly enhanced peroxisome proliferator-activated receptors transcriptional activity with EC50 values of 18.26-31.45 μM. The anthraquinone derivatives were the active components from the roots of P. multiflorum as an inhibitor on inflammation-related factors in human hepatoma cells. Therefore, we suggest that the roots of P. multiflorum can be used to treat natural inflammatory diseases. This study presented that fifteen compounds (1-15) isolated from the roots of Polygonum multiflrum exert signifiant anti inflmmatory effects by inhibiting TNF α induced NF κB activation and PPARs transcription. Abbreviation used: NF κB: Nuclear factor kappa B, PPARs: Peroxisome proliferator activated receptors, PPREs: Peroxisome proliferator response elements, TNF α: Tumor necrosis factor α, ESI-MS: Electrospray ionization mass spectrometry, HepG2: Human hepatoma cells.

  13. In vitro evaluation of antileishmanial activity and toxicity of essential oils of Artemisia absinthium and Echinops kebericho.

    Science.gov (United States)

    Tariku, Yinebeb; Hymete, Ariaya; Hailu, Asrat; Rohloff, Jens

    2011-04-01

    Potential toxicity, costs, and drug-resistant pathogens necessitate the development of new antileishmanial agents. Medicinal and aromatic plants constitute a major source of natural organic compounds. In this study, essential oils of Artemisia absinthium L. and Echinops kebericho Mesfin were investigated by GC and GC/MS analyses. Isolated oils were screened for antileishmanial activity against two Leishmania strains (L. aethiopica and L. donovani), and toxicity on the human monocytic leukemia (THP-1) cell line and red blood cells in vitro. GC/MS Analysis revealed 65 compounds (93.74%) for Artemisia absinthium and 43 compounds (92.85%) for Echinops kebericho oil. The oils contained the oxygenated monoterpene camphor (27.40%) and the sesquiterpene lactone dehydrocostus lactone (41.83%) as major constituents, respectively. Both oils showed activity against promastigote (MIC 0.0097-0.1565 μl/ml) and axenic amastigote forms (EC(50) 0.24-42.00 nl/ml) of both leishmania species. Weak hemolytic effect was observed for both oils, showing a slightly decreased selectivity index (SI 0.8-19.2) against the THP-1 cell line. Among the two oils tested, E. kebericho exerted strong antileishmanial activity that was even higher than that of amphotericin B with significant cytotoxicity. This study, therefore, demonstrated the potential use of both oils as source of novel agents for the treatment of leishmaniasis. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

  14. Nutritional composition and antioxidant activity of four tomato (Lycopersicon esculentum L.) farmer' varieties in Northeastern Portugal homegardens.

    Science.gov (United States)

    Pinela, José; Barros, Lillian; Carvalho, Ana Maria; Ferreira, Isabel C F R

    2012-03-01

    The nutritional and antioxidant composition of four tomato Portuguese farmer' varieties widely cultivated in homegardens was determined. The analysed components included macronutrients, individual profiles of sugars and fatty acids by chromatographic techniques, hydrophilic antioxidants such as vitamin C, phenolics, flavonols and anthocyanins, and lipophilic antioxidants such as tocopherols, β-carotene and lycopene. Furthermore, the antioxidant activity was evaluated through DPPH scavenging activity, reducing power, β-carotene bleaching inhibition and TBARS formation inhibition. One of the four varieties, which is locally known as round tomato or potato tomato, proved to be the most powerful in antioxidant activity (EC50 values≤1.63 mg/ml), phenolic compounds (phenolics 31.23 mg ClAE/g extract, flavonols 6.36 mg QE/g extract and anthocyanins 3.45 mg ME/g extract) and carotenoids (β-carotene 0.51 mg/100 g and lycopene 9.49 mg/100 g), while the so-called yellow tomato variety revealed interesting nutritional composition, including higher fructose (3.42 g/100 g), glucose (3.18 g/100 g), α-linolenic acid (15.53%) and total tocopherols (1.44 mg/100 g) levels. Overall, these farmer' varieties of garden tomato cultivated in the Northeastern Portuguese region could contribute as sources of important antioxidants related to the prevention of chronic diseases associated to oxidative stress, such as cancer and coronary artery disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

    Directory of Open Access Journals (Sweden)

    Thi Thanh Hoang Nguyen

    2013-01-01

    Full Text Available The substantia gelatinosa (SG of the trigeminal subnucleus caudalis (Vc has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM and almost completely blocked by strychnine (2 μM, suggesting that taurine-mediated responses are via glycine receptor (GlyR activation. In addition, taurine (1 mM activated extrasynaptic GABAA receptor (GABAAR-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons.

  16. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

    Science.gov (United States)

    Bhattarai, Janardhan Prasad; Park, Soo Joung; Han, Seong Kyu

    2013-01-01

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC) with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM) showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM) and almost completely blocked by strychnine (2 μM), suggesting that taurine-mediated responses are via glycine receptor (GlyR) activation. In addition, taurine (1 mM) activated extrasynaptic GABAA receptor (GABAAR)-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons. PMID:24379976

  17. Identification and Optimization of Benzimidazole Sulfonamides as Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists with in Vivo Activity.

    Science.gov (United States)

    Hennessy, Edward J; Oza, Vibha; Adam, Ammar; Byth, Kate; Castriotta, Lillian; Grewal, Gurmit; Hamilton, Geraldine A; Kamhi, Victor M; Lewis, Paula; Li, Danyang; Lyne, Paul; Öster, Linda; Rooney, Michael T; Saeh, Jamal C; Sha, Li; Su, Qibin; Wen, Shengua; Xue, Yafeng; Yang, Bin

    2015-09-10

    We report here a novel series of benzimidazole sulfonamides that act as antagonists of the S1P1 receptor, identified by exploiting an understanding of the pharmacophore of a high throughput screening (HTS)-derived series of compounds described previously. Lead compound 2 potently inhibits S1P-induced receptor internalization in a cell-based assay (EC50 = 0.05 μM), but has poor physical properties and metabolic stability. Evolution of this compound through structure-activity relationship development and property optimization led to in vivo probes such as 4. However, this compound was unexpectedly found to be a potent CYP3A inducer in human hepatocytes, and thus further chemistry efforts were directed at addressing this liability. By employing a pregnane X receptor (PXR) reporter gene assay to prioritize compounds for further testing in human hepatocytes, we identified lipophilicity as a key molecular property influencing the likelihood of P450 induction. Ultimately, we have identified compounds such as 46 and 47, which demonstrate the desired S1P1 antagonist activity while having greatly reduced risk of CYP3A induction in humans. These compounds have excellent oral bioavailability in preclinical species and exhibit pharmacodynamic effects of S1P1 antagonism in several in vivo models following oral dosing. Relatively modest antitumor activity was observed in multiple xenograft models, however, suggesting that selective S1P1 antagonists would have limited utility as anticancer therapeutics as single agents.

  18. Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury

    Directory of Open Access Journals (Sweden)

    Shixin Liu

    2015-02-01

    Full Text Available In this work, we designed and synthesized a series of amide derivatives (1–13, benzoxazine derivatives (16–28 and amino derivatives (29–30 from xyloketal B. All 28 new derivatives and seven known compounds (14, 15, 31–35 were evaluated for their protection against H2O2-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC50 values of them and the leading compound 31 (xyloketal B were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B were further to examine in the JC-1 mitochondrial membrane potential (MMP assay of HUVECs using flow cytometry (FCM. The result indicated that 23 and 24 significantly inhibited H2O2-induced decrease of the cell mitochondrial membrane potential (ΔΨm at 25 μM. Collectively, the protective effects of xyloketals on H2O2-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP.

  19. Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities.

    Science.gov (United States)

    Otero, Elver; García, Elisa; Palacios, Genesis; Yepes, Lina M; Carda, Miguel; Agut, Raúl; Vélez, Iván D; Cardona, Wilson I; Robledo, Sara M

    2017-12-01

    The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were active against L. (V) panamensis (18-23, 26 and 30) and eight of them against T. cruzi (19-22, 24 and 28-30) with EC 50 values lower than 40 μM. Compounds 19-22, 24 and 28-30 showed higher activities than benznidazole (BNZ). Esters 19 and 21 were the most active compounds for both L. (V) panamensis and T. cruzi with 3.82 and 11.65 μM and 8.25 and 8.69 μM, respectively. Compounds 19-22, 24 and 28-30 showed higher activities than benznidazole (BNZ). Most of the compounds showed antiprotozoal activity and with exception of 18, 26 and 28, the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19, bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

    Science.gov (United States)

    Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

    2017-07-01

    Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

  1. HPTLC-profiling of eleutherosides, mechanism of antioxidative action of eleutheroside E1, the PAMPA test with LC/MS detection and the structure–activity relationship

    Directory of Open Access Journals (Sweden)

    Daniel Załuski

    2018-03-01

    Full Text Available Human body is constantly generating free radicals, which causes oxidative stress. Despite naturally occurring antioxidant systems in human body, free radicals cause lipid, proteins and DNA oxidation. New antioxidants are still urgent as well as their mechanisms of action should be explained. In this study, we investigated the mechanism by which eleutherosides B, E and E1 may act as antioxidants, identified eleutherosides in Eleutherococcus lasiogyne and Eleutherococcus giraldii, and explained in vitro the absorption of eleutheroside E1 based on passive transport. The DPPH∗ and DB-HPTLC tests were used to assess the antioxidant activity. Of the three eleutherosides, only eleutheroside E1 exhibited a strong anti-DPPH∗ activity (EC50 37.03 μg/mL; 63 mMol compared to the raw extracts (EC50 170 and 180 μg/mL for E. lasiogyne and E. giraldii. This activity was also confirmed by the DB-HPTLC autography technique. According to Załuski’s hypothesis, the antioxidant mechanism of eleutheroside E1 is based on the complexation of DPPH∗ molecule with its aryl radical. During this reaction, the aryl radical of eleutheroside E1 (E1∗ and DPPHH are created. Next, the aryl radical (E1∗ is complexed with another DPPH∗ molecule. Additionally, the aryl radical can be stabilized by the presence of the methoxy groups in the aromatic ring, which increases its antioxidative action. The HPTLC-identification of extracts showed the presence of eleutherosides B, E and E1 in both species. The PAMPA test coupled with LC/MS detection showed a low permeability of eleutheroside E1 across artificial membrane. Because eleutherosides belong to the polyphenols, the TPC and TFC were quantified. The TPC and TFC varied from 51.4 to 49.3 mg/g dry extract for TPC, and from 5.73 to 4.91 mg/g dry extract for TFC, for E. giraldii and E. lasiogyne, respectively. In conclusion, eleutheroside E1 in its pure form could be a chemopreventive ingredient of new pharmacological

  2. Synthesis, Antimicrobial, Antioxidant and Nematicidal Activity of (2E,4E)-5-(Benzo(d) (1,3)dioxol-5yl)penta-2,4-dienamides

    International Nuclear Information System (INIS)

    Wahab, A.; Sultana, A.; Sherwani, S. K.; Perveen, Z.; Khan, K. M.; Karim, A.; Taha, M.

    2015-01-01

    The amides of piperic acid have been synthesized via the condensation of piperic acid with amines. The structural characterization was done by IR, 1H-NMR, EI-MS and elemental analysis. The amides 3a-3o were evaluated for their biological activity. It has been found that among others the newly synthesized compound 3f, 3k, 3m, and 3o have great potential against root-knot nematode Meloidogyne incognita that usually affect tomato crop. These compounds exhibited 92, 96, 82 and 95% mortality rate at lethal concentration (LC50) 4.4, 3.4, 4.5 and 3.5 mg/mL, respectively. Conventionally used nematicide furadan was taken as standard. Compound 3h, 3c and, 3j exhibited significant anti-oxidant activities against 1,1-diphenylpicrylhydrazil (DPPH) radical with 80, 70 and 72% inhibition (EC50 = 625, 937 and 937.5 micro g/mL), respectively. Ascorbic acid was used as standard. When tested for antimicrobial activity 3m was found to be the most active one showing zone of inhibition in the range of 18-30 mm against all tested microbial strains. Good biological activities of synthetic amides indicate their ability to behave as a good antimicrobial and nematicidal agent. (author)

  3. Development of an in vitro system to assess the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on B lymphocyte activation and differentiation

    International Nuclear Information System (INIS)

    Clark, G.C. Jr.

    1988-01-01

    Humoral immunity appears to be a sensitive target for chemical induced immunosuppression. Therefore, in vitro methodologies were developed to assess the effects of environmental chemicals on B lymphocyte activation and differentiation. The environmental chemical, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was used to develop these methodologies. The in vitro humoral immune response of purified B cells to the T-independent antigen TNP-LPS was suppressed in a dose dependent manner with an EC 50 of 10 nM TCDD. A polyclonal activation system using anti-immunoglobulin and T cell derived factors was used to further analyze B lymphocyte suppression by TCDD. The activation and proliferation responses of B lymphocytes were not affected by TCDD as monitored by the incorporation of 3 H-uridine and 3 H-thymidine or expression of the cell surface markers Ia and the IL-2 receptor. Terminal differentiation was selectively inhibited by TCDD as assessed by a dose dependent inhibition of immunoglobulin synthesis and expression of the cell surface marker PC.2. Protein phosphorylation, an early event in lymphocyte activation, was altered by exposure to TCDD and was associated with a dose dependent increase in the activity of tyrosine-specific protein kinases

  4. Synthesis and Ativiral Activity of 5-(Benzylthio)-4-carbamyl-1,2,3-triazoles Against Human Cytomegalovirus (CMV) and Varicella-zoster Virus (VZV).

    Science.gov (United States)

    Wen, Yi-Ning; Zhang, Zhi-Feng; Liu, Ning-Ning; Andrei, Graciela; Snoeck, Robert; Xiang, Yu-Hong; Schols, Dominique; Chen, Xue; Zhang, Zhuo-Yong; Zhang, Qing-Shan; Wu, Qin-Pei

    2017-01-01

    All of the clinical drugs for herpesvirus infections exhibit high toxicity and suffer from significant drug-resistantance. There is a great need for the development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action. A series of novel 5-(benzylthio)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against human cytomegalovirus (HCMV), varicella-zoster virus (VZV) and herpes simplex virus (HSV) were evaluated in vitro. Some compounds possess antiviral activity. Compound 7f exhibits promising inhibitory activity against both HCMV and VZV. Our results also indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. 4,5-Bissubstiuted triazoles are active against herpesviruses and the nature and the position of substituents in the benzene ring remarkably affect their activity, such as bromo, cyano and cyanovynil substituents. Future studies should be undertaken to investigate the mechanism of action of these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Quantitative comparison of fire danger index performance using fire activity

    CSIR Research Space (South Africa)

    Steenkamp, KC

    2012-07-01

    Full Text Available and in logistic planning of fire fighting resources. In this study historical fire activity from remotely sensed data are compared with various FDIs to identify which index has the strongest statistical relationship with fire occurrences and therefore the highest...

  6. TRPA1 agonist activity of probenecid desensitizes channel responses: consequences for screening.

    Science.gov (United States)

    McClenaghan, Conor; Zeng, Fanning; Verkuyl, Jan Martin

    2012-12-01

    The transient receptor potential channel subtype A member 1 (TRPA1) is a nonselective cation channel widely viewed as having therapeutic potential, particularly for pain-related indications. Realization of this potential will require potent, selective modulators; however, currently the pharmacology of TRPA1 is poorly defined. As TRPA1 is calcium permeable, calcium indicators offer a simple assay format for high-throughput screening. In this report, we show that probenecid, a uricosuric agent used experimentally in screening to increase loading of calcium-sensitive dyes, activates TRPA1. Prolonged probenecid incubation during the dye-loading process reduces agonist potency upon subsequent challenge. When Chinese Hamster Ovary (CHO)-hTRPA1 or STC-1 cells, which endogenously express TRPA1, were dye loaded in the presence of 2 mM probenecid TRPA1, agonists appeared less potent; EC(50) for allyl isothiocyante agonists in CHO-hTRPA1 was increased from 1.5±0.19 to 7.32±1.20 μM (P<0.01). No significant effect on antagonist potency was observed when using the agonist EC(80) concentration determined under the appropriate dye-loading conditions. We suggest an alternative protocol for calcium imaging using another blocker of anion transport, sulfinpyrazone. This blocker significantly augments indicator dye loading and the screening window, but is not a TRPA1 agonist and has no effect on agonist potency.

  7. Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

    Science.gov (United States)

    Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik

    2017-07-01

    After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural diverse polymers which are capable to estimate green algae growth inhibition (EC50). The model (N = 43, R 2  = 0.73, RMSE = 0.28) is a regression-based decision tree using one structural descriptor for each of three polymer classes separated based on charge. The QSAR is applicable to linear homo polymers as well as copolymers and does not require information on the size of the polymer particle or underlying core material. Highly branched polymers, non-nitrogen cationic polymers and polymeric surfactants are not included in the model and thus cannot be evaluated. The model works best for cationic and non-ionic polymers for which cellular adsorption, disruption of the cell wall and photosynthesis inhibition were the mechanisms of action. For anionic polymers, specific properties of the polymer and test characteristics need to be known for detailed assessment. The data and QSAR results for anionic polymers, when combined with molecular dynamics simulations indicated that nutrient depletion is likely the dominant mode of toxicity. Nutrient depletion in turn, is determined by the non-linear interplay between polymer charge density and backbone flexibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Activated sludge respirometry to assess solar detoxification of a metal finishing effluent

    International Nuclear Information System (INIS)

    Santos-Juanes, L.; Amat, A.M.; Arques, A.; Bernabeu, A.; Silvestre, M.; Vicente, R.; Ano, E.

    2008-01-01

    Inhibition of the respiration of activated sludge has been tested as a convenient method to estimate toxicity of aqueous solutions containing copper and cyanide, such as metal finishing effluents; according to this method, an EC 50 of 0.5 mg/l was determined for CN - and 3.0 mg/l for copper. Solar detoxification of cyanide-containing solutions was studied using TiO 2 , but this process was unfavourable because of the inhibitory role that plays the copper ions present in real effluents on the oxidation of cyanide. On the other hand, the oxidative effect of hydrogen peroxide was greatly enhanced by Cu 2+ and solar irradiation, as complete elimination of free and complexed cyanide could be accomplished, together with precipitation of copper, in experiments carried out at pilot plant scale with real metal finishing effluents. Under these conditions, total detoxification was achieved according to respirometric measurements although some remaining toxicity was determined by more sensitive Vibrio fischeri luminescent assay

  9. Aortic Relaxant Activity of Crataegus gracilior Phipps and Identification of Some of Its Chemical Constituents

    Directory of Open Access Journals (Sweden)

    Abigail Hernández-Pérez

    2014-12-01

    Full Text Available This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior on isolated rat aorta, and on the purification and identification of some of their secondary metabolites by the use of chromatographic and spectroscopic techniques. The results obtained showed that the methanol extract has a significantly more potent and effective vasorelaxant effect than the other tested extracts, with an EC50 = 8.69 ± 4.34 µg/mL and an Emax = 94.6% ± 11.30%, values that are close to that of acetylcholine, the positive control. From the same extract, two major triterpenes were isolated and identified as ursolic and corosolic acids by comparison of their experimental NMR spectroscopic data with those reported in the literature. Chlorogenic acid, rutin, quercetin, kaempferol and (+-catechin were also identified using HPLC coupled with PDAD. All these compounds have already been proven to possess on their own antihypertensive effect and other benefits on cardiovascular diseases and they can support, at least in part, the traditional use of this plant species.

  10. Diterpenoids from Streptomyces sp. SN194 and Their Antifungal Activity against Botrytis cinerea.

    Science.gov (United States)

    Bi, Yuhui; Yu, Zhiguo

    2016-11-16

    Botrytis cinerea is a serious phytopathogen affecting a wide range of crops around the world. Many fungicides targeting Botrytis cinerea have failed due to the pathogen's genetic plasticity. In an effort to search for new fungicides from natural products, two new diterpenoids, named chloroxaloterpin A, 1, and B, 2, were isolated from culture broth of Streptomyces sp. SN194 along with four known diterpenoids, viguiepinol, 3, and oxaloterpins C-E, 4-6. Their structures were elucidated based on extensive MS, NMR, and X-ray crystallography analyses. Both the [(2-chlorophenyl)amino]carbonyl carbanic acyl group in 1 and the 2-[(2-chlorophenyl)amino]-2-oxo-acetyl group in 2 are discovered in natural products for the first time. All six compounds were tested against Botrytis cinerea, and chloroxaloterpin A, 1, and B, 2, demonstrated strong inhibitory activity against spore germination with EC 50 of 4.40 and 4.96 μg/mL, respectively.

  11. Prediction of toxicity of phenols and anilines to algae by quantitative structure-activity relationship.

    Science.gov (United States)

    Lu, Guang-Hua; Wang, Chao; Guo, Xiao-Ling

    2008-06-01

    To measure the toxicity of phenol, aniline, and their derivatives to algae and to assess, model, and predict the toxicity using quantitative structure-activity relationship (QSAR) method. Oxygen production was used as the response endpoint for assessing the toxic effects of chemicals on algal photosynthesis. The energy of the lowest unoccupied molecular orbital (E(LUMO)) and the energy of the highest occupied molecular orbital (E(HOMO)) were obtained from the ChemOffice 2004 program using the quantum chemical method MOPAC, and the frontier orbital energy gap (deltaE) was obtained. The compounds exhibited a reasonably wide range of algal toxicity. The most toxic compound was alpha-naphthol, whereas the least toxic one was aniline. A two-descriptor model was derived from the algal toxicity and structural parameters: log1/EC50 = 0.268,logKow - 1.006deltaE + 11.769 (n = 20, r2 = 0.946). This model was stable and satisfactory for predicting toxicity. CONCLUSION Phenol, aniline, and their derivatives are polar narcotics. Their toxicity is greater than estimated by hydrophobicity only, and addition of the frontier orbital energy gap deltaE can significantly improve the prediction of logKow-dependent models.

  12. The Fungicidal Activity of Thymol against Fusarium graminearum via Inducing Lipid Peroxidation and Disrupting Ergosterol Biosynthesis

    Directory of Open Access Journals (Sweden)

    Tao Gao

    2016-06-01

    Full Text Available Thymol is a natural plant-derived compound that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism for thymol against phytopathogens remains unclear. In this study, we identified the antifungal action of thymol against Fusarium graminearum, an economically important phytopathogen showing severe resistance to traditional chemical fungicides. The sensitivity of thymol on different F. graminearum isolates was screened. The hyphal growth, as well as conidial production and germination, were quantified under thymol treatment. Histochemical, microscopic, and biochemical approaches were applied to investigate thymol-induced cell membrane damage. The average EC50 value of thymol for 59 F. graminearum isolates was 26.3 μg·mL−1. Thymol strongly inhibited conidial production and hyphal growth. Thymol-induced cell membrane damage was indicated by propidium iodide (PI staining, morphological observation, relative conductivity, and glycerol measurement. Thymol induced a significant increase in malondialdehyde (MDA concentration and a remarkable decrease in ergosterol content. Taken together, thymol showed potential antifungal activity against F. graminearum due to the cell membrane damage originating from lipid peroxidation and the disturbance of ergosterol biosynthesis. These results not only shed new light on the antifungal mechanism of thymol, but also imply a promising alternative for the control of Fusarium head blight (FHB disease caused by F. graminearum.

  13. Direct activation of protein kinase C by 1 alpha,25-dihydroxyvitamin D3.

    Science.gov (United States)

    Slater, S J; Kelly, M B; Taddeo, F J; Larkin, J D; Yeager, M D; McLane, J A; Ho, C; Stubbs, C D

    1995-03-24

    The key metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 (1,25-D3), induces rapid cellular responses that constitute a so-called "non-genomic" response. This effect is distinguished from its "classic" genomic role in calcium homeostasis involving the nuclear 1,25-D3 receptor. Evidence is presented that protein kinase C (PKC) is directly activated by 1,25-D3 at physiological concentrations (EC50 = 16 +/- 1 nM). The effect was demonstrable with single PKC-alpha, -gamma, and -epsilon isoform preparations, assayed in a system containing only purified enzyme, substrate, co-factors, and lipid vesicles, from which it is inferred that a direct interaction with the enzyme is involved. The finding that calcium-independent isoform PKC-epsilon was also activated by 1,25-D3 shows that the calcium binding C2 domain is not required. The level of 1,25-D3-induced activation, paired with either diacylglycerol or 4 beta-12-O-tetradecanoylphorbol-13-acetate, was greater than that achievable by any individual activator alone, each at a saturating concentration, a result that implies two distinct activator sites on the PKC molecule. Phosphatidylethanolamine present in the lipid vesicles potentiated 4 beta-12-O-tetradecanoylphorbol-13-acetate- and diacylglycerol-induced PKC activities, whereas 1,25-D3-induced activity decreased, consistent with 1,25-D3-activated PKC possessing a distinct conformation. The results suggest that PKC is a "membrane-bound receptor" for 1,25-D3 and that it could be important in the control of non-genomic cellular responses to the hormone.

  14. Tea and herbal infusions: Their antioxidant activity and phenolic profile

    International Nuclear Information System (INIS)

    Atoui, A.; Mansouri, A.; Panagiotis Kefalas; Boskou, G.

    2005-01-01

    Tea and herbal infusions have been studied for their polyphenolic content, antioxidant activity and phenolic profile. The total phenolics recovered by ethyl acetate from the water extract, were determined by the Folin-Ciocalteu procedure and ranged from 88.1 ± 0.42 (Greek mountain tea) to 1216 ± 32.0 mg (Chinese green tea) GAE (Gallic acid equivalents)/cup. The antioxidant activity was evaluated by two methods, DPPH and chemiluminescence assays, using Trolox and quercetin as standards. The EC50 of herbal extracts ranged from 0.151 ± 0.002 mg extract/mg DPPH (0.38 quercetin equivalents and 0.57 Trolox equivalents), for Chinese green tea, to 0.77 ± 0.012 mg extract/mg DPPH (0.08 quercetin equivalents and 0.13 Trolox equivalents), for Greek mountain tea. Chemiluminescence assay results showed that the IC50 ranged from 0.17 ± 3.4 x 103 lg extract/ml of the final solution in the measuring cell (1.89 quercetin and 5.89 Trolox equivalents) for Chinese green tea, to 1.10 ± 1.86 x 102 g extract/ml of the final solution in the measuring cell (0.29 quercetin and 0.90 Trolox equivalents) for Greek mountain tea. The phenolic profile in the herbal infusions was investigated by LC-DAD-MS in the positive electrospray ionization (ESI) mode. About 60 different flavo- noids, phenolic acids and their derivatives have been identified. (author)

  15. Antimicrobial activities of some mushrooms in Turkey.

    Science.gov (United States)

    Doğan, Hasan Hüseyin; Duman, Rüstem; Özkalp, Birol; Aydin, Sema

    2013-06-01

    Terfezia boudieri Chatin (Pezizaceae), Agaricus brunnescens Peck (Agaricaceae) and Lactarius vellereus (Fr.) Fr. (Russulaceae) are well-known species in Turkey, and are used both for food and traditional medicine. The powdered fruit bodies of T. boudieri, A. brunnescens and L. vellereus were used to evaluate the antimicrobial activities. Chloroform, acetone and methanol extracts of T. boudieri, A. brunnescens and L. vellereus were tested for their antimicrobial activities against four Gram-positive bacteria, five Gram-negative bacteria and yeast using a micro-dilution method. The strongest minimum inhibitory concentration (MIC) value observed against the test microorganisms was with the chloroform extract of T. boudieri (MIC 2.4 µg/mL) against Streptococcus pyogenes. Maximum antimicrobial effects were observed with the acetone extracts of T. boudieri and L. vellereus (MIC 4.8 µg/mL) against Bacillus subtilis. The strongest antifungal activity was observed with the acetone extracts of T. boudieri (MIC 2.4 µg/mL) and A. brunnescens (MIC 19.5 µg/mL) against Candida albicans. The strongest MIC values for all fungal extracts were observed between 78 and 2.4 µg/mL. Present results demonstrated that these three mushroom species have excellent antimicrobial and antifungal activities, and thus have great potential as a source for natural health products.

  16. Histamine modulates cell growth, reactive oxygen species production and activity of antioxidant enzymes in human cell lines

    International Nuclear Information System (INIS)

    Medina, V.; Cricco, G.; Garbarino, G.; Nunez, M.; Martin, G.; Cocca, C.; Bergoc, R.M.; Rivera, E.S.

    2004-01-01

    Full text: In the present work, the capacity of Histamine (HA) to modulate cell proliferation and ROS production as well as the receptors involved in this response was investigated. Mammary normal (HBL-100) and malignant cell lines (MDA-MB-231, MCF- 7) was employed. The levels of the free radicals superoxide (O 2 - ) and hydrogen peroxide (H 2 O 2 ) and intracellular HA content were determined by flow cytometry. The activity of antioxidant enzymes, super-oxide dismutase (SOD) and catalase (CAT) were determined by kinetic spectrophotometric techniques. Cell proliferation was evaluated by the clonogenic assay. Cell lines presented intracellular levels of HA directly correlated with their malignancy. In MDA-MB-231, HA via H 2 R increased cAMP levels (EC 50 0.45 μM) producing in turn a significant inhibition on cell proliferation (p 1 R, stimulated cell growth. H 2 O 2 levels resulted inversely correlated with cell proliferation while O 2 - remained unchanged. Furthermore, HA significantly modified the activity of SOD and CAT. In normal HBL-100, HA modulates cell proliferation but in exactly the opposite range of doses. The effect on cell growth was inversely correlated with H 2 O 2 levels. The present data indicate that histamine can modulate cell proliferation via H 1 R and H 2 R. This effect is exerted in part by the modulation of antioxidant enzymes and ROS production. (author)

  17. P-Glycoprotein-Activity Measurements in Multidrug Resistant Cell Lines: Single-Cell versus Single-Well Population Fluorescence Methods

    Directory of Open Access Journals (Sweden)

    Jennifer Pasquier

    2013-01-01

    Full Text Available Background. P-gp expression has been linked to the efflux of chemotherapeutic drugs in human cancers leading to multidrug resistance. Fluorescence techniques have been widely applied to measure the P-gp activity. In this paper, there is a comparison between the advantages of two fluorescence approaches of commonly available and affordable instruments: the microplate reader (MPR and the flow cytometer to detect the P-gp efflux activity using calcein-AM. Results. The selectivity, sensibility, and reproducibility of the two methods have been defined. Our results showed that the MPR is more powerful for the detection of small inhibition, whereas the flow cytometry method is more reliable at higher concentrations of the inhibitors. We showed that to determine precisely the inhibition efficacy the flow cytometry is better; hence, to get the correct Emax and EC50 values, we cannot only rely on the MPR. Conclusion. Both techniques can potentially be used extensively in the pharmaceutical industry for high-throughput drug screening and in biology laboratories for academic research, monitoring the P-gp efflux in specific assays.

  18. ATP induces NO production in hippocampal neurons by P2X(7 receptor activation independent of glutamate signaling.

    Directory of Open Access Journals (Sweden)

    Juan Francisco Codocedo

    Full Text Available To assess the putative role of adenosine triphosphate (ATP upon nitric oxide (NO production in the hippocampus, we used as a model both rat hippocampal slices and isolated hippocampal neurons in culture, lacking glial cells. In hippocampal slices, additions of exogenous ATP or 2'(3'-O-(4-Benzoylbenzoyl ATP (Bz-ATP elicited concentration-dependent NO production, which increased linearly within the first 15 min and plateaued thereafter; agonist EC50 values were 50 and 15 µM, respectively. The NO increase evoked by ATP was antagonized in a concentration-dependent manner by Coomassie brilliant blue G (BBG or by N(ω-propyl-L-arginine, suggesting the involvement of P2X7Rs and neuronal NOS, respectively. The ATP induced NO production was independent of N-methyl-D-aspartic acid (NMDA receptor activity as effects were not alleviated by DL-2-Amino-5-phosphonopentanoic acid (APV, but antagonized by BBG. In sum, exogenous ATP elicited NO production in hippocampal neurons independently of NMDA receptor activity.

  19. Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin.

    Science.gov (United States)

    Liu, Tao; Ma, Ming; Ge, Hui-Ming; Yang, Chunying; Cleveland, John; Shen, Ben

    2015-11-01

    Leinamycin (LNM, 1) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4'-dideshydroxy-LNM (5) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1; 5 exhibits comparable activity as 1 with the EC50 values between 8.21 and 275 nM. This work reveals new insight into the structure-activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Prediction of the antiglycation activity of polysaccharides from Benincasa hispida using a response surface methodology.

    Science.gov (United States)

    Jiang, Xiang; Kuang, Fei; Kong, Fansheng; Yan, Chunyan

    2016-10-20

    Benincasa hispida is a popular vegetable in China. Our previous experiments suggested that polysaccharides isolated from B. hispida fruits (PBH) have antiglycation effect and DPPH free radical scavenging activity. Ultrasonic treatments can be used to extract polysaccharides from Benincasa hispida (PBH). The aim of this study was to investigate the correlation between the ultrasonic treatment conditions and the antiglycation activity of PBH. A mathematical model was generated with an artificial neural network (ANN) toolbox from MATLAB to analyze the effects of ultrasonic treatment conditions on antiglycation activity. The response surface plots showed relationships between ultrasonic extraction conditions and bioactivity. The R(2) value of the model was 0.9919, which suggested good fitness of the neural network. The application of genetic algorithms showed that the optimal ultrasonic extraction conditions resulted in the highest antiglycation activity for PBH. These were 150W, 46°C, and 35min. These conditions produced a predicted antiglycation activity of 41.2%; the actual activity was 40.9% under optimal conditions. This is very close to the predicted value. The experimental data indicated that the PBH possessed both antiglycation and antioxidant activities. The maximum actual value of antiglycation was 101.7% that of the positive control, and the PBH inhibited the DPPH free radicals with an EC50 value of 0.98mg/mL. This is 66.2% that of ascorbic acid. These results explained the observations that B. hispida can decrease glucose levels in diabetic patients. The experimental results also showed that the ANN could be used for optimization and prediction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Effect of chromium oxide (III) nanoparticles on the production of reactive oxygen species and photosystem II activity in the green alga Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Cristina Henning da [Department of Sanitary and Environmental Engineering, Federal University of Santa Catarina, Campus Universitário, CEP: 88040-970, Florianópolis, SC (Brazil); Perreault, François [School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85287-3005 (United States); Oukarroum, Abdallah [Department of Chemistry, University of Quebec in Montréal, 2101, Jeanne Mance Street, Station Centre-Ville, Montréal, QC H2X 2J6 (Canada); Melegari, Sílvia Pedroso [Department of Sanitary and Environmental Engineering, Federal University of Santa Catarina, Campus Universitário, CEP: 88040-970, Florianópolis, SC (Brazil); Center of Marine Studies, Federal University of Parana, Beira-mar Avenue, 83255-976, Pontal do Parana, PR (Brazil); Popovic, Radovan [Department of Chemistry, University of Quebec in Montréal, 2101, Jeanne Mance Street, Station Centre-Ville, Montréal, QC H2X 2J6 (Canada); Matias, William Gerson, E-mail: william.g.matias@ufsc.br [Department of Sanitary and Environmental Engineering, Federal University of Santa Catarina, Campus Universitário, CEP: 88040-970, Florianópolis, SC (Brazil)

    2016-09-15

    With the growth of nanotechnology and widespread use of nanomaterials, there is an increasing risk of environmental contamination by nanomaterials. However, the potential implications of such environmental contamination are hard to evaluate since the toxicity of nanomaterials if often not well characterized. The objective of this study was to evaluate the toxicity of a chromium-based nanoparticle, Cr{sub 2}O{sub 3}-NP, used in a wide diversity of industrial processes and commercial products, on the unicellular green alga Chlamydomonas reinhardtii. The deleterious impacts of Cr{sub 2}O{sub 3}-NP were characterized using cell density measurements, production of reactive oxygen species (ROS), esterase enzymes activity, and photosystem II electron transport as indicators of toxicity. Cr{sub 2}O{sub 3}-NP exposure inhibited culture growth and significantly lowered cellular Chlorophyll a content. From cell density measurements, EC50 values of 2.05 ± 0.20 and 1.35 ± 0.06 g L{sup −1} Cr{sub 2}O{sub 3}-NP were obtained after 24 and 72 h of exposure, respectively. In addition, ROS levels were increased to 160.24 ± 2.47% and 59.91 ± 0.15% of the control value after 24 and 72 h of exposition to 10 g L{sup −1} Cr{sub 2}O{sub 3}-NP. At 24 h of exposure, the esterase activity increased to 160.24% of control value, revealing a modification of the short-term metabolic response of algae to Cr{sub 2}O{sub 3}-NP exposure. In conclusion, the metabolism of C. reinhardtii was the most sensitive to Cr{sub 2}O{sub 3}-NP after 24 h of treatment. - Highlights: • Cr{sub 2}O{sub 3} nanoparticles are unstable and form large aggregates in the medium. • EC50 for growth inhibition of C. reinhardtii is 1.35 g L{sup −1} at 72 h. • Cr{sub 2}O{sub 3} nanoparticles increase ROS levels at 10 g L{sup −1}. • Cr{sub 2}O{sub 3} nanoparticles affect photosynthetic electron transport.

  2. PAM-1616, a selective peroxisome proliferator-activated receptor γ modulator with preserved anti-diabetic efficacy and reduced adverse effects.

    Science.gov (United States)

    Kim, Mi-Kyung; Chae, Yu Na; Choi, Song-hyen; Moon, Ho Sang; Son, Moon-Ho; Bae, Myung-Ho; Choi, Hyun-ho; Hur, Youn; Kim, Eunkyung; Park, Yoo Hoi; Park, Chan Sun; Kim, Jae Gyu; Lim, Joong In; Shin, Chang Yell

    2011-01-15

    Peroxisome proliferator-activated receptor (PPAR) γ is known to be a key regulator of insulin resistance. PAM-1616 is a novel, non-thiazolidinedione small molecule compound synthesized in Dong-A Research Center. In this study, we characterized the pharmacological and safety profiles of PAM-1616 as a selective PPARγ modulator. PAM-1616 selectively binds to human PPARγ (IC(50), 24.1±5.6 nM) and is a partial agonist for human PPARγ with an EC(50) of 83.6±43.7 nM and a maximal response of 24.9±7.1% relative to the full agonist, rosiglitazone. PAM-1616 was selective for human PPARγ than for human PPARα (EC(50), 2658±828 nM) without activating human PPARδ, which makes it a selective modulator of PPARγ. Treatment of high fat diet-induced obese C57BL/6J mice with PAM-1616 for 21 days improved HOMA-IR. Furthermore, PAM-1616 significantly improved hyperglycemia in db/db mice with little side effect when orally administered at a dose of 1 mg/kg/day for 28 days. Intriguingly, PAM-1616 was seen to increase the gene expression of inducible glucose transporter (GLUT4), while it partially induced that of a fatty acid carrier, aP2 in 3T3-L1 adipocytes, and it also showed partial recruitment of an adipogenic cofactor, TRAP220 as compared to rosiglitazone. PAM-1616 did not cause a significant increase in plasma volume of ICR mice when orally administered at a dose of 10 mg/kg/day for 9 days. PAM-1616 increased the expression of fluid retention-inducing genes such as serum/glucocorticoid-regulated kinase (SGK)-1 to a lesser extent as compared to rosiglitazone in human renal epithelial cells. These results suggest that PAM-1616 acts as a selective modulator of PPARγ with excellent antihyperglycemic property. The differential modulation of target gene by PAM-1616 might contribute to the improved side effect profiles. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Correlation between 96-h mortality and 24-h acetylcholinesterase inhibition in three grass shrimp larval life stages.

    Science.gov (United States)

    Key, Peter B; Fulton, Michael H

    2006-03-01

    Three life stages of larval grass shrimp were tested to determine whether acetylcholinesterase (AChE) activity expressed as 24-h sublethal effect endpoints (EC20 and EC50) could be used to predict 96-h mortality (lowest observable effect concentration (LOEC) and LC50) for shrimp exposed to three organophosphate insecticides. With regard to mortality, newly hatched larvae and 18-day-old larvae were the most sensitive in the malathion and azinphosmethyl exposures. In the chlorpyrifos exposures, newly hatched larvae and postlarvae were the most sensitive life stages. Results of the 24-h AChE inhibition tests showed that newly hatched larvae were generally more sensitive in the three organophosphate exposures. A regression analysis of the EC50's and LC50's yielded the strongest correlation with R2=0.987 (correlation coefficient=0.994 and 95% confidence intervals 0.969-0.999). The LOEC/EC20 relationship yielded R2=0.962. For these grass shrimp life stages and pesticides, sublethal effect endpoints could be used as a predictor of 96-h mortality.

  4. Azidoblebbistatin, a photoreactive myosin inhibitor

    Science.gov (United States)

    Képiró, Miklós; Várkuti, Boglárka H.; Bodor, Andrea; Hegyi, György; Drahos, László; Kovács, Mihály; Málnási-Csizmadia, András

    2012-01-01

    Photoreactive compounds are important tools in life sciences that allow precisely timed covalent crosslinking of ligands and targets. Using a unique technique we have synthesized azidoblebbistatin, which is a derivative of blebbistatin, the most widely used myosin inhibitor. Without UV irradiation azidoblebbistatin exhibits identical inhibitory properties to those of blebbistatin. Using UV irradiation, azidoblebbistatin can be covalently crosslinked to myosin, which greatly enhances its in vitro and in vivo effectiveness. Photo-crosslinking also eliminates limitations associated with the relatively low myosin affinity and water solubility of blebbistatin. The wavelength used for photo-crosslinking is not toxic for cells and tissues, which confers a great advantage in in vivo tests. Because the crosslink results in an irreversible association of the inhibitor to myosin and the irradiation eliminates the residual activity of unbound inhibitor molecules, azidoblebbistatin has a great potential to become a highly effective tool in both structural studies of actomyosin contractility and the investigation of cellular and physiological functions of myosin II. We used azidoblebbistatin to identify previously unknown low-affinity targets of the inhibitor (EC50 ≥ 50 μM) in Dictyostelium discoideum, while the strongest interactant was found to be myosin II (EC50 = 5 μM). Our results demonstrate that azidoblebbistatin, and potentially other azidated drugs, can become highly useful tools for the identification of strong- and weak-binding cellular targets and the determination of the apparent binding affinities in in vivo conditions. PMID:22647605

  5. Human sperm immobilizing activity of aminophenyl arsenic acid and its N-substituted quinazoline, pyrimidine, and purine derivatives: protective effect of glutathione.

    Science.gov (United States)

    Uckun, Fatih M; Liu, Xing Ping; D'Cruz, Osmond J

    2002-01-01

    We examined the potential toxicity of pentavalent organic arsenicals for human sperm. We used computer-assisted sperm analysis to examine the effects of three aminophenyl arsenicals and their nine N-substituted quinazoline, pyrimidine, and purine derivatives on human sperm motility and kinematics in human semen and medium. Among the arsenicals examined, (aminophenylazo)-phenyl arsonic acid and its N-substituted pyrimidine derivative PHI-370 (2-methylthio-4-[(4'-aminophenylazo)-phenylarsonic acid] pyrimidine) exhibited rapid sperm immobilizing activity in medium with EC(50) values of 77 and 82 microM, respectively, and t(1/2) of 7 Debyes). Sperm immobilizing activity of these arsenicals was completely abrogated in the presence of seminal plasma. Furthermore, coincubation of motile sperm with PHI-370 in the presence of reduced glutathione (GSH) resulted in dose-dependent protection of sperm motility and sperm motion parameters. Coincubation of the arsenical with GSH at a molar ratio of 1:20 resulted in 95% retention of sperm progressive motility. The mean values of the other sperm movement characteristics also showed > 90% protection. These observations suggest that the rapid sperm immobilizing activity of these pentavalent arsenicals may be as a result of direct binding of the arsenical with the sperm thiol components essential for sperm motility as well as induction of oxidative damage by disruption of sperm cell's antioxidant system. Sodium arsanilate and its N-substituted pyrimidine derivative, PHI-370, are useful probes to further evaluate the mechanism of pentavalent arsanilate-induced human sperm dysfunction.

  6. Antifungal Activity and Action Mode of Cuminic Acid from the Seeds of Cuminum cyminum L. against Fusarium oxysporum f. sp. Niveum (FON Causing Fusarium Wilt on Watermelon

    Directory of Open Access Journals (Sweden)

    Yang Sun

    2017-11-01

    Full Text Available In order to develop a novel biofungicide, the antifungal activity and action mode of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f. sp. niveum (FON on watermelon was determined systematically. In this study, the median effective concentration (EC50 value for cuminic acid in inhibiting mycelial growth of FON was 22.53 μg/mL. After treatment with cuminic acid, the mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid were significantly decreased. Synthesis genes of bikaverin (Bike1, Bike2 and Bike3 and fusaric acid (FUB1, FUB2, FUB3 and FUB4 both were downregulated compared with the control, as confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content were observed after in vivo cuminic acid treatment on watermelon leaves. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON.

  7. Antifungal Activity and Action Mode of Cuminic Acid from the Seeds of Cuminum cyminum L. against Fusarium oxysporum f. sp. Niveum (FON) Causing Fusarium Wilt on Watermelon.

    Science.gov (United States)

    Sun, Yang; Wang, Yong; Han, Li Rong; Zhang, Xing; Feng, Jun Tao

    2017-11-30

    In order to develop a novel biofungicide, the antifungal activity and action mode of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f. sp. niveum (FON) on watermelon was determined systematically. In this study, the median effective concentration (EC 50 ) value for cuminic acid in inhibiting mycelial growth of FON was 22.53 μg/mL. After treatment with cuminic acid, the mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid) were significantly decreased. Synthesis genes of bikaverin ( Bike1 , Bike2 and Bike3 ) and fusaric acid ( FUB1 , FUB2 , FUB3 and FUB4 ) both were downregulated compared with the control, as confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content were observed after in vivo cuminic acid treatment on watermelon leaves. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON.

  8. Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model

    Directory of Open Access Journals (Sweden)

    Jian-Hui Xiao

    2012-01-01

    Full Text Available Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC50 values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands.

  9. Measuring children's physical activity

    DEFF Research Database (Denmark)

    Schneller, Mikkel Bo; Bentsen, Peter; Nielsen, Glen

    2017-01-01

    INTRODUCTION: Accelerometer-based physical activity monitoring has become the method of choice in many large-scale physical activity (PA) studies. However, there is an ongoing debate regarding the placement of the device, the determination of device wear time, and how to solve a lack of participant...... on the thigh (n=903) and one on the lower back (n= 856), for up to ten consecutive days. Participants were instructed not to reattach an accelerometer should it fall off. Simple and multiple linear regression were used to determine associations between accelerometer wear time and age, sex, BMI percentiles......, and PA level. RESULTS: Over 65% had >7 days of uninterrupted, 24h wear time for the thigh location, and 59.5% for the lower back location. From multiple linear regressions, PA levels showed the strongest association with lower wear time (thigh: β=-.231, R=.066; lower back: β=-.454, R=.126). In addition...

  10. In vitro antioxidant, anti-inflammatory, cytotoxic activities against prostate cancer of extracts from Hibiscus sabdariffa leaves.

    Science.gov (United States)

    Worawattananutai, Patsorn; Itharat, Arunporn; Ruangnoo, Srisopa

    2014-08-01

    Hibiscus sabdariffa (HS) leaves are a vegetable, which is used as a healthy sour soup for protection against chronic diseases in Thai traditional medicine. To investigate antioxidant, anti-inflammatory and cytotoxic activities of Hibiscus sabdariffa leave extracts from diferent extraction methods. Fresh and dry Hibiscus sabdariffa leaves were extracted by various methods such as maceration with 95% and 50% ethanol, squeeze, and boiling with water or decoction. All extracts were testedfor antioxidant activity by using DPPH radical scavenging assay, anti-inflammatory activity by determination on inhibitory effect of nitric oxide production on RAW264. 7 cell. Cytotoxic activity also tested against human prostate cancer cell line (PC-3) by using sulforhodamine B (SRB) assay. Total phenolic content determined by the Folin-Ciocalteu colorimetric method. The results found that the 95% ethanolic extract of Hibiscus sabdariffa dried leaves (HSDE95) showed the highest antioxidant activity with an EC50 of 34.51±2.62 μg/ml and had the highest phenolic content (57.00±3.73 mg GAE/g). HSDE95 also showed potent cytotoxicity against prostate cancer cell line with an IC50 of 8.58±0.68 μg/ml whereas HSDE95 and all of extracts ofHibiscus sabdariffa leaves had no anti-inflammatory activity. The obtained results revealed that HSDE95 extract showedpotent cytotoxic activity against prostate cancer cells but low antioxidant and anti-inflammatory activities. This extract should be further isolated as active compounds against prostate cancer.

  11. Machine learning models identify molecules active against the Ebola virus in vitro [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2017-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  12. Machine learning models identify molecules active against the Ebola virus in vitro [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-10-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  13. Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.

    2003-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate CAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of CAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of CAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of CAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of CAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of CAMP by either epinephrine or isoproterenol.

  14. Effects of garlic and diallyl trisulfide on the growth, photosynthesis, and alkaline phosphatase activity of the toxic cyanobacterium Microcystis aeruginosa.

    Science.gov (United States)

    Wang, Shoubing; Wang, Yuanan; Ma, Xiaoxue; Xu, Ziran

    2016-03-01

    To identify a botanical algicide and elucidate the response of cyanobacteria to the extract from higher plants, the effects of garlic and garlic-derived diallyl trisulfide on Microcystis aeruginosa were studied. Effects were evaluated by changes in cell density, chlorophyll a, maximum effective quantum yield (Fv/Fm), effective quantum yield (YII), non-photochemical quenching (NPQ), and rapid light curves of M. aeruginosa. In addition, alkaline phosphatase activity (APA) was measured when M. aeruginosa was incubated with diallyl trisulfide. Results indicated that the inhibition by garlic and diallyl trisulfide was significant. The 120-h 50 % effective concentrations of garlic and diallyl trisulfide (EC50) were 0.75 g L(-1) and 2.84 mg L(-1), respectively. Moreover, the inhibitory rate increased with increasing concentration and the growth of M. aeruginosa was inhibited by 90.0 % at the highest concentrations. We also show that the response of M. aeruginosa to stress could involve both impairment of the photosynthetic center PSII and alteration of APA. For example, at high garlic concentration (2.0 g L(-1)), Fv/Fm significantly decreased from 0.501 to 0.084 (p garlic as an environmentally friendly algicide.

  15. Discovery of a New Fungicide Candidate through Lead Optimization of Pyrimidinamine Derivatives and Its Activity against Cucumber Downy Mildew.

    Science.gov (United States)

    Guan, Aiying; Wang, Mingan; Yang, Jinlong; Wang, Lizeng; Xie, Yong; Lan, Jie; Liu, Changling

    2017-12-13

    Downy mildew is one of the most highly destructive of the diseases that cause damage to fruits and vegetables. Because of the continual development of resistance, it is important to discover new fungicides with different modes of action from existing fungicides for the control of downy mildew. This study is a continuation of our previous work on the novel pyrimidinamine lead compound, 9, and includes field trials for the identification of the optimal candidate. A new compound, 1c, was obtained, which gave a lower EC 50 value (0.10 mg/L) against downy mildew than lead compound 9 (0.19 mg/L) and the commercial fungicides diflumetorim, dimethomorph, and cyazofamid (1.01-23.06 mg/L). Compound 1c displayed similar broad-spectrum fungicidal activity to compound 9 but better field efficacy than compound 9, cyazofamid, and flumorph. The present work indicates that pyrimidinamine compound 1c is a candidate for further development as a commercial fungicide for the control of downy mildew.

  16. Lersivirine, a Nonnucleoside Reverse Transcriptase Inhibitor with Activity against Drug-Resistant Human Immunodeficiency Virus Type 1▿ ‡

    Science.gov (United States)

    Corbau, Romuald; Mori, Julie; Phillips, Chris; Fishburn, Lesley; Martin, Alex; Mowbray, Charles; Panton, Wendy; Smith-Burchnell, Caroline; Thornberry, Adele; Ringrose, Heather; Knöchel, Thorsten; Irving, Steve; Westby, Mike; Wood, Anthony; Perros, Manos

    2010-01-01

    The nonnucleoside reverse transcriptase inhibitors (NNRTIs) are key components of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus type 1 (HIV-1). A major problem with the first approved NNRTIs was the emergence of mutations in the HIV-1 reverse transcriptase (RT), in particular K103N and Y181C, which led to resistance to the entire class. We adopted an iterative strategy to synthesize and test small molecule inhibitors from a chemical series of pyrazoles against wild-type (wt) RT and the most prevalent NNRTI-resistant mutants. The emerging candidate, lersivirine (UK-453,061), binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC50s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets. Altogether lersivirine is a highly potent and selective NNRTI, with excellent efficacy against NNRTI-resistant viruses. PMID:20660667

  17. Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1.

    Science.gov (United States)

    Corbau, Romuald; Mori, Julie; Phillips, Chris; Fishburn, Lesley; Martin, Alex; Mowbray, Charles; Panton, Wendy; Smith-Burchnell, Caroline; Thornberry, Adele; Ringrose, Heather; Knöchel, Thorsten; Irving, Steve; Westby, Mike; Wood, Anthony; Perros, Manos

    2010-10-01

    The nonnucleoside reverse transcriptase inhibitors (NNRTIs) are key components of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus type 1 (HIV-1). A major problem with the first approved NNRTIs was the emergence of mutations in the HIV-1 reverse transcriptase (RT), in particular K103N and Y181C, which led to resistance to the entire class. We adopted an iterative strategy to synthesize and test small molecule inhibitors from a chemical series of pyrazoles against wild-type (wt) RT and the most prevalent NNRTI-resistant mutants. The emerging candidate, lersivirine (UK-453,061), binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC(50)s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets. Altogether lersivirine is a highly potent and selective NNRTI, with excellent efficacy against NNRTI-resistant viruses.

  18. Antioxidant capacity and larvicidal activity of essential oil and extracts from Lippia grandis

    Directory of Open Access Journals (Sweden)

    Evelyn Ivana T. Damasceno

    2011-02-01

    Full Text Available The leaves and thin branches of Lippia grandis Schauer, Verbenaceae, are used for flavoring of food in the Brazilian Amazon, as substitute for oregano. In this study the constituents of the essential oil were identified and the antioxidant capacity and larvicidal activity of the oil and methanol extract and its sub-fractions were evaluated. A sensory evaluation was determined in view of absence of toxicity. The oil showed a yield of 2.1% and its main constituents were thymol (45.8%, p-cymene (14.3%, γ-terpinene (10.5%, carvacrol (9.9% and thymol methyl ether (4.8%, totalizing 85%. The DPPH radical scavenging activity showed values for the EC50 between 9.0 and 130.5 µg mL-1 and the TEAC/ABTS values varied from 131.1 to 336.0 mg TE/g, indicating significant antioxidant activity for the plant. The total phenolic content ranged from 223.0 to 761.4 mg GAE/g, contributing to the antioxidant activity observed. The crude extracts inhibited the bleaching of β-carotene and the oil showed the greatest inhibition (42.5%. The oil (LgO, 7.6±2.4 µg mL-1 showed strong larvicidal activity against the brine shrimp bioassay. The sensory evaluation was highly satisfactory in comparison to oregano. The results are very promising for the use of L. grandis in seasoning and antioxidant products.

  19. Phytochemicals Screening and Activities of Hydrophilic and Lipophilic Antioxidant of Some Fruit Peels

    International Nuclear Information System (INIS)

    Khairusy Syakirah Zulkifli; Noriham Abdullah; Aminah Abdullah; Nurain Aziman; Wan Saidatul Syida Wan Kamarudin

    2012-01-01

    This study was conducted to screen the secondary metabolites compounds including alkaloids, tannins, saponins and flavonoids as well as to determine the antioxidant activities of four types of fruit peels namely Psidium guajava (guava), Mangifera indica (Chakonan mango), Citrus sinensis (Navel orange) and Malus sylvestris (Granny Smith apple). The hydrophilic and lipophilic antioxidant activities were investigated using three different assays such as Ferric Reducing Antioxidant Power (FRAP), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and Oxygen Radical Absorbance Capacity (ORAC). Total Phenolic Content (TPC) and Total Flavonoids Content (TFC) were also conducted and the correlations between the antioxidant assays with TPC and TFC were evaluated. The TPC in the peels extract ranged between 204.90 to 517.00 mg GAE/ g extract weight while TFC ranged between 97.48 to 177.86 mg QE/ g extract weight. The FRAP, EC 50 scavenging activity and ORAC values were 18.78 to 45.36 mM TE/ 100 g extract weight, 0.146 to 0.717 mg/ ml scavenging effect and 37.54 to 60.59 μM TE/ g extract weight respectively. The extract of M. indica peels appeared to be as potent as ascorbic acid with maximum inhibition of 74 % at 200 ppm. M. indica peels showed highest value in all antioxidant assays and in TPC while the highest in TFC was found in M. sylvestris peels. There were strong correlations between all antioxidant assays with TPC but very weak correlations with TFC. This study suggested that the extracts of fruit peels are convenient to be use as functional ingredients in food product development as they are rich in antioxidant activities. (author)

  20. Enhanced antimicrobial activity of novel synthetic peptides derived from vejovine and hadrurin.

    Science.gov (United States)

    Sánchez-Vásquez, Lorenzo; Silva-Sanchez, Jesus; Jiménez-Vargas, Juana Maria; Rodríguez-Romero, Adela; Muñoz-Garay, Carlos; Rodríguez, Maria C; Gurrola, Georgina B; Possani, Lourival D

    2013-06-01

    Microbial antibiotic resistance is a challenging medical problem nowadays. Two scorpion peptides displaying antibiotic activity: hadrurin and vejovine were taken as models for the design of novel shorter peptides with similar activity. Using the standard Fmoc-based solid phase synthesis technique of Merrifield twelve peptides (18 to 29 amino acids long) were synthesized, purified and assayed against a variety of multi-drug resistant Gram-negative bacteria from clinical isolates. Hemolytic and antiparasitic activities of the peptides and their possible interactions with eukaryotic cells were verified. Release of the fluorophore calcein from liposomes treated with these peptides was measured. A peptide with sequence GILKTIKSIASKVANTVQKLKRKAKNAVA), and three analogs: Δ(Α29), Δ(K12-Q18; Ν26-Α29), and K4N Δ(K12-Q18; Ν26-Α29) were shown to inhibit the growth of Gram-negative (E. coli ATCC25922) and Gram-positive bacteria (S. aureus), as well as multi-drug resistant (MDR) clinical isolated. The antibacterial and antiparasitic activities were found with peptides at 0.78 to 25μM and 5 to 25μM concentration, respectively. These peptides have low cytotoxic and hemolytic activities at concentrations significantly exceeding their minimum inhibitory concentrations (MICs), showing values between 40 and 900μM for their EC50, compared to the parent peptides vejovine and hadrurin that at the same concentration of their MICs lysed more than 50% of human erythrocytes cells. These peptides promise to be good candidates to combat infections caused by Gram-negative bacteria from nosocomial infections. Our results confirm that well designed synthetic peptides can be an alternative for solving the lack of effective antibiotics to control bacterial infections. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization.

    Science.gov (United States)

    Liu, Zhaoqiang; Chen, Wenmin; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

    2014-11-24

    Through a structure-based molecular hybridization approach, a novel series of diarylnicotinamide derivatives (DANAs) targeting the entrance channel of HIV-1 NNRTIs binding pocket (NNIBP) were rationally designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells together with the inhibition against the reverse transcriptase (RT) in an enzymatic assay. Encouragingly, most of the new DANAs were found to be active against wild-type HIV-1 with an EC50 in the range of 0.027-4.54 μM. Among them, compound 6b11 (EC50 = 0.027 μM, SI > 12518) and 6b5 (EC50 = 0.029 μM, SI = 2471) were identified as the most potent inhibitors, which were more potent than the reference drugs nevirapine (EC50 = 0.31 μM) and delavirdine (EC50 = 0.66 μM). Some DANAs were also active at micromolar concentrations against the K103N + Y181C resistant mutant. Compound 6b11 exhibited the highest enzymatic inhibition activity (IC50 = 20 nM), which is equal to that of efavirenz (EC50 = 20 nM) and 31 times higher than that of nevirapine (EC50 = 0.62 μM). Preliminary structure-activity relationships (SARs) and molecular modeling of these new DANAs have been discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Sesquiterpene lactone containing extracts from two cultivars of forage chicory (Cichorium intybus) show distinctive chemical profiles and in vitro activity against Ostertagia ostertagi.

    Science.gov (United States)

    Peña-Espinoza, Miguel; Boas, Ulrik; Williams, Andrew R; Thamsborg, Stig M; Simonsen, Henrik T; Enemark, Heidi L

    2015-12-01

    The study investigated direct anthelmintic effects of sesquiterpene lactones (SL)-containing extracts from forage chicory against free-living and parasitic stages of Ostertagia ostertagi. Freeze-dried leaves from chicory cultivars 'Spadona' and 'Puna II' were extracted using methanol/water. Total SL were further fractionated by solid-phase extraction and resulting extracts were characterised by high-performance liquid chromatography (HPLC). O. ostertagi eggs from faeces of mono-infected calves were hatched and L1 were used in a larval feeding inhibition assay (LFIA), while cultured L3 were used in a larval exsheathment inhibition assay (LEIA). Adult worms were immediately recovered after slaughter and used for motility inhibition assays (AMIA). Electron microscopy (EM) was performed on adult O. ostertagi exposed to 1000 μg extract mL(-1) of both chicory cultivars. In all assays, decreasing concentrations of SL-containing extracts in PBS (1% DMSO) were tested in replicates with 1% DMSO in PBS as negative controls. HPLC demonstrated similar concentrations of most SL in both extracts. However, Spadona-extract contained significantly higher concentrations of 11, 13-dihydro-8-deoxylactucin (P = 0.01), while Puna II-extract had increased levels of 11, 13-dihydrolactucin (P LFIA, both extracts reduced larval feeding at increasing concentrations, but Spadona-extract showed higher potency confirmed by significantly lower EC50 (P  0.05). In the AMIA, both SL-containing extracts induced a dose-dependent effect but Spadona-extract showed greater activity and exerted faster worm paralysis than Puna II-extract with significantly lower EC50 (P < 0.0001). No cuticular damage was observed by EM in worms exposed to any of the extracts. We have demonstrated that SL-containing extracts from forage chicory can inhibit feeding of free-living larvae and exert direct effects against parasitic stages of O. ostertagi. Our results may contribute to the identification of natural

  3. Synthesis, structural characterization and antioxidant activity of some vanadium(IV), Mo(VI)/(IV) and Ru(II) complexes of pyridoxal Schiff base derivatives

    Science.gov (United States)

    Elsayed, Shadia A.; Noufal, Aya M.; El-Hendawy, Ahmed M.

    2017-09-01

    New complexes containing vanadium(IV), Mo(VI)/(IV) and Ru(II) derived from Schiff base of pyridoxal and S-benzyldithiocarbazate (H2pysb) or p-toluidine (Hpytol) have been prepared. The structures of the described compounds were elucidated by elemental analyses, spectroscopic techniques (IR, 1H NMR, UV-Vis and EPR) magnetism, molar conductivity and thermal analysis measurements. Their redox behaviors were also studied by cyclic voltammetry. The ligand H2pysb showed coordination to the metal ions in a dibasic tridenate manner through deprotonated phenolate oxygen, azomethine nitrogen and thiolate sulfur, while Hpytol behaved as monobasic bidentate through phenolate oxygen and azomethine nitrogen. The complexes were tested for their antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and the data obtained revealed that the scavenging activity of the complexes towards DPPH is high for the oxovanadium(IV) complexes with lower IC50 values which are comparable to ascorbic acid as a standard antioxidant. The EC50 concentration ratio together with other antioxidant parameters are also reported.

  4. Ultrasonic-assisted enzymatic extraction of phenolics from broccoli (Brassica oleracea L. var. italica) inflorescences and evaluation of antioxidant activity in vitro.

    Science.gov (United States)

    Wu, Hao; Zhu, Junxiang; Yang, Long; Wang, Ran; Wang, Chengrong

    2015-06-01

    An efficient ultrasonic-assisted enzymatic extraction technique was applied to extracting phenolics from broccoli inflorescences without organic solvents. The synergistic model of enzymolysis and ultrasonication simultaneously was selected, and the enzyme combination was optimized by orthogonal test: cellulase 7.5 mg/g FW (fresh weight), pectinase 10 mg/g FW, and papain 1.0 mg/g FW. The operating parameters in ultrasonic-assisted enzymatic extraction were optimized with response surface methodology using Box-Behnken design. The optimal extraction conditions were as follows: ultrasonic power, 440 W; liquid to material ratio, 7.0:1 mL/g; pH value of 6.0 at 54.5 ℃ for 10 min. Under these conditions, the extraction yield of phenolics achieved 1.816 ± 0.0187 mg gallic acid equivalents/gram FW. The free radical scavenging activity of ultrasonic-assisted enzymatic extraction extracts was determined by 1,1-diphenyl-2-picrylhydrazyl·assay with EC50 values of 0.25, and total antioxidant activity was determined by ferric reducing antioxidant power assay with ferric reducing antioxidant power value of 0.998 mmol FeSO4/g compared with the referential ascorbic acid of 1.184 mmol FeSO4/g. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.

    Science.gov (United States)

    von Bueren, A O; Schlumpf, M; Lichtensteiger, W

    2008-01-01

    Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

  6. An image-based algorithm for precise and accurate high throughput assessment of drug activity against the human parasite Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Seunghyun Moon

    Full Text Available We present a customized high content (image-based and high throughput screening algorithm for the quantification of Trypanosoma cruzi infection in host cells. Based solely on DNA staining and single-channel images, the algorithm precisely segments and identifies the nuclei and cytoplasm of mammalian host cells as well as the intracellular parasites infecting the cells. The algorithm outputs statistical parameters including the total number of cells, number of infected cells and the total number of parasites per image, the average number of parasites per infected cell, and the infection ratio (defined as the number of infected cells divided by the total number of cells. Accurate and precise estimation of these parameters allow for both quantification of compound activity against parasites, as well as the compound cytotoxicity, thus eliminating the need for an additional toxicity-assay, hereby reducing screening costs significantly. We validate the performance of the algorithm using two known drugs against T.cruzi: Benznidazole and Nifurtimox. Also, we have checked the performance of the cell detection with manual inspection of the images. Finally, from the titration of the two compounds, we confirm that the algorithm provides the expected half maximal effective concentration (EC50 of the anti-T. cruzi activity.

  7. An image-based algorithm for precise and accurate high throughput assessment of drug activity against the human parasite Trypanosoma cruzi.

    Science.gov (United States)

    Moon, Seunghyun; Siqueira-Neto, Jair L; Moraes, Carolina Borsoi; Yang, Gyongseon; Kang, Myungjoo; Freitas-Junior, Lucio H; Hansen, Michael A E

    2014-01-01

    We present a customized high content (image-based) and high throughput screening algorithm for the quantification of Trypanosoma cruzi infection in host cells. Based solely on DNA staining and single-channel images, the algorithm precisely segments and identifies the nuclei and cytoplasm of mammalian host cells as well as the intracellular parasites infecting the cells. The algorithm outputs statistical parameters including the total number of cells, number of infected cells and the total number of parasites per image, the average number of parasites per infected cell, and the infection ratio (defined as the number of infected cells divided by the total number of cells). Accurate and precise estimation of these parameters allow for both quantification of compound activity against parasites, as well as the compound cytotoxicity, thus eliminating the need for an additional toxicity-assay, hereby reducing screening costs significantly. We validate the performance of the algorithm using two known drugs against T.cruzi: Benznidazole and Nifurtimox. Also, we have checked the performance of the cell detection with manual inspection of the images. Finally, from the titration of the two compounds, we confirm that the algorithm provides the expected half maximal effective concentration (EC50) of the anti-T. cruzi activity.

  8. Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

    International Nuclear Information System (INIS)

    Mosaddeghi, M.

    1989-01-01

    The function of α 1 -adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with [ 3 H]inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 μM potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC 50 was decreased from 3.93 ± 0.42 to 1.91 ± 0.31 μM NE. Concentrations of 0.1-100 μM and 0.1-10 μM cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 μM NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 μM prazosin. Cocaine (10 μM) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 μM prazosin. [ 3 H]Prazosin saturation and NE [ 3 H]prazosin competition binding studies using crude membrane preparations showed that 10 μM cocaine did not alter binding parameters B max , K d , Hill slope, and IC 50 . Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis

  9. Phytochemical Profiles and Antioxidant Activities in Six Species of Ramie Leaves

    Science.gov (United States)

    Chen, Yongsheng; Wang, Gaoyan; Wang, Hong; Cheng, Chaohua; Zang, Gonggu; Guo, Xinbo; Liu, Rui Hai

    2014-01-01

    Increased consumption of vegetables or plant food has been associated with decreased risk of developing major chronic diseases, such as cancers, diabetes, cardiovascular diseases, and age-related functional decline. Ramie leaves are rich in phenolics and flavonoids, which have been suggested for human health benefits. Phenolic contents, flavonoid contents, phenolic compounds, and anti-cancer properties in six species of ramie leaves were analyzed by Folin-reagent method, sodium borohydride/chloranil-based assay (SBC), HPLC method and antiproliferation, cytoxicity, respectively. Antioxidant activities were measured through peroxyl radical scavenging capacity (PSC) method, oxygen radical absorbance capacity (ORAC) method, and cellular antioxidant activity (CAA). Research indicated that Boehmeria penduliflora contained the highest total phenolic content (2313.7±27.28 mg GAE/100 g FW), and flavonoid content (1682.4±27.70 mg CAE/100 g FW). Boehmeria tricuspis showed the highest PSC value (9574.8±117.63 µM vit. C equiv./100 g FW), while Boehmeria penduliflora indicated the highest ORAC value (330.44±16.88 µmol Trolox equiv./g FW). The antioxidant activities were correlated with phenolic contents and flavonoid contents. Boehmeria tricuspis had the highest antiproliferative capacity with the lowest EC50 (4.11±0.19 mg/mL). The results for the analyzed ramie for CAA were significantly different from each other (panalysis. Our research is the first report to study the phytochemical profiles and antioxidant activities in different species of ramie leaves for their health benefit. PMID:25243741

  10. Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus

    Directory of Open Access Journals (Sweden)

    Yong-Zhe Zhu

    2018-03-01

    Full Text Available The human β-site amyloid cleaving enzyme (BACE1 has been considered as an effective drug target for treatment of Alzheimer’s disease (AD. In this study, Urechis unicinctus (U. unicinctus, which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4-en-3-one, cholesta-4,6-dien-3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, 1H, and 13C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11 and published values. Hecogenin and cholest-4-en-3-one showed significant inhibitory activity against BACE1 with EC50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6-dien-3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli, Salmonella enterica (S. enterica, Pasteurella multocida (P. multocida, and Physalospora piricola (P. piricola, with minimal inhibitory concentration (MIC ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

  11. Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus.

    Science.gov (United States)

    Zhu, Yong-Zhe; Liu, Jing-Wen; Wang, Xue; Jeong, In-Hong; Ahn, Young-Joon; Zhang, Chuan-Jie

    2018-03-14

    The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer's disease (AD). In this study, Urechis unicinctus (U. unicinctus) , which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4- en -3-one, cholesta-4,6- dien -3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, ¹H, and 13 C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11) and published values. Hecogenin and cholest-4- en -3-one showed significant inhibitory activity against BACE1 with EC 50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6- dien -3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli) , Salmonella enterica (S. enterica) , Pasteurella multocida (P. multocida) , and Physalospora piricola (P. piricola) , with minimal inhibitory concentration (MIC) ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

  12. Anti-Trypanosoma cruzi activity in vitro of phases and isolated compounds from Excoecaria lucida leaves.

    Science.gov (United States)

    da Silva, Cristiane Franca; Pacheco, Ania Ochoa; Alves, Rayane Nogueira; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Arranz, Julio Cesar Escalona

    2018-01-11

    Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. This illness is found mainly in 21 Latin American countries and an estimated 8 million people are infected worldwide. The unsatisfactory chemotherapy provokes severe toxicity and resistant strains. Medicinal plants constitute a promising source of new drugs and remedies against all kinds of disorders, mainly infectious diseases arousing interest worldwide. The aim of this study has been the isolation, structural identification and evaluation of the trypanocidal activity of samples present in the Excoecaria lucida Sw. leaves. Total extract (TE) of E. lucida Sw. leaves was obtained by ethanol extract therefore fractionated sequentially with hexane, ethyl acetate and n-butanol, to obtain three phases: Hex, EA and But, respectively. Ellagic acid (EL1) was purified from both EA and But phases, while EL2; a 1:1 stigmasterol-3-O-β-D-glucopyranoside plus sitosterol-3-O-β-D-glucopyranoside mixture was obtained from the Hex phase. Activity assays was performed using bloodstream and intracellular forms of T. cruzi and cytotoxicity assays using L929 fibroblasts. The EL1 and EL2 samples were more active against bloodstream trypomastigote forms with EC50 of 53.0±3.6 and 58.2±29.0 µg/mL, respectively; at 100 µg/mL. These samples also shown 70% of inhibition of L929 cells infection. Toxicity assays demonstrated that after 96 h of treatment only the fractions Hex and EA presented detectable cytotoxicity. ellagic acid, stigmasterol-3-O-β-D-glucopyranoside and sitosterol-3-O-β-D-glucopyranoside are reported for the first time in E. lucida Sw. leaves as well as their biological activity studies supporting further investigations for Chagas disease treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Antioxidant and Antimicrobial Activities of 7-Hydroxy-calamenene-Rich Essential Oils from Croton cajucara Benth.

    Directory of Open Access Journals (Sweden)

    Celuta S. Alviano

    2013-01-01

    Full Text Available Croton cajucara is a shrub native to the Amazon region locally known as “sacaca”. Two morphotypes are known: white and red “sacaca”. The essential oils (EO obtained by hydrodistillation from leaves of the red morphotype were, in general, rich in 7-hydroxycalamenene (28.4%–37.5%. The effectiveness of these EO regarding the antimicrobial activity against pathogenic microorganisms was initially investigated by the drop test method, showing significant inhibition zones. Among the microorganisms tested, the essential oils rich in 7-hydroxycalamenene were more effective against methicillin resistant Staphylococcus aureus (MRSA, Enterococcus faecalis, Mycobacterium tuberculosis, M. smegmatis, Mucor circinelloides and Rhizopus oryzae. The minimum inhibitory concentrations (MIC of the oils were determined using the broth dilution assay. It was possible to observe that 7-hydroxycalamenene-rich oils presented high antimicrobial activity, with MIC of 4.76 × 10−3 μg/mL for MRSA, 4.88 μg/mL for M. tuberculosis, 39.06 μg/mL for M. smegmatis, and 0.152 μg/mL for R. oryzae and 3.63 × 10−8 μg/mL for M. circinelloides. The antioxidant activity of this EO suggests that 7-hydroxycalamenene provides more antioxidant activity according with EC50 less than 63.59 μg/mL. Considering the bioactive potential of EOs and 7-hydroxycalamenene could be of great interest for development of antimicrobials for therapeutic use in treatment of bacterial and fungal infections in humans and/or veterinary practice.

  14. Antioxidant, antimutagenic and antiproliferative activities in selected seaweed species from Sinaloa, Mexico.

    Science.gov (United States)

    Osuna-Ruiz, Idalia; López-Saiz, Carmen-María; Burgos-Hernández, Armando; Velázquez, Carlos; Nieves-Soto, Mario; Hurtado-Oliva, Miguel A

    2016-10-01

    Context Seaweeds from the Mexican Pacific Ocean have not been evaluated as a source of chemoprotectants. Objective The objective of this study is to evaluate chemopreventive activities of the seaweeds Phaephyceae - Padina durvillaei (Dictyotaceae) - Rodhophyceae - Spyridia filamentosa (Spyridiaceae), Gracilaria vermiculophylla (Gracilariaceae) - and Chlorophyceae - Ulva expansa (Ulvaceae), Codium isabelae (Codiaceae), Rhizoclonium riparium (Cladophoraceae) and Caulerpa sertularioides (Caulerpaceae). Materials and methods Methanol, acetone and hexane seaweed extracts were assessed at 30 and 3 mg/mL on antioxidant capacity (DPPH and ABTS assays), 0.003-3.0 mg/plate on antimutagenic activity against AFB1 using Salmonella typhimurium TA98 and TA100 tester strains in Ames test, and 12.5 to 100 μg/mL on antiproliferative activity on Murine B-cell lymphoma. Phenols, flavonoids and pigments content were also assessed as antioxidant compounds. Results Extraction yield was higher in methanol than in acetone and hexane extracts (6.4, 2.7 and 1.4% dw). Antioxidant capacity was higher in brown and green than in red seaweed species, particularly in P. durvillaei extracted in acetone (EC50  value= 16.9 and 1.56 mg/mL for DPPH and ABTS). Flavonoids and chlorophylls were identified as mainly antioxidant components; particularly in hexane extracts, which were correlated with the antioxidant capacity. Highest mutagenesis inhibition (> 40%) occurred in R. riparium at the lowest concentration assayed (0.003 mg/plate), while highest antiproliferative inhibition (37 and 72% for 12.5 and 25 μg/mL) occurred in C. sertularioides. Discussion and conclusion Flavonoids and chlorophylls explained the chemopreventive activities assessed in S. filamentosa, R. riparium and C. sertularioides. These seaweeds have a high potential as a source of novel chemoprotectants.

  15. Inhibitory effect on nitric oxide production and free radical scavenging activity of Thai medicinal plants in osteoarthritic knee treatment.

    Science.gov (United States)

    Anuthakoengkun, Areeya; Itharat, Arunporn

    2014-08-01

    Thai medicine plants used for Osteoarthritis of knee (OA) treatment consist of twelve plants such as Crinumn asiaticum, Cleome viscosa, Drypetes roxburghii, Piper longum, Piper nigrum, Plumbago indica, Alpinia galanga, Curcuma aromatica, Globba malaccensis, Zingiber montanum, Zingiber officinale andZingiberzerumbet. They showedhighfrequency in OA formula. To investigate inhibitory effect on LPS-induced nitric oxide (NO) release from RAW264. 7 cell and free radical scavenging activity usingDPPH assay of these ethanolic plant extracts. Plant materials were extracted by maceration in 95% ethanol. Anti-inflammatory activity were tested on LPS-induced NO production. Free radical scavenging activity was performed by DPPH assay. All of ethanolic extracts exhibited potent inhibitory effect on NO release. The ethanolic extract of Z. zerumbet exhibited the highest inhibitory effect followed by Z. montanum and G. malaccensis, respectively. Except A. galanga and C. viscosa, all extracts possessed more influential than indomethacin (IC50 = 20.32±3.23 μLg/ml), a positive control. The investigation on antioxidant activity suggested that the ethanolic extracts of D. roxburghii, Z. officinale, Z. montanum, C. aromatic, A. galanga, P indica, G malaccensis, P nigrum exhibited antioxidant activity. By means ofD. roxburghii had the highest electron donating activity,followed by Z. officinale. Moreover both extracts were more effective than BHT apositive control (EC50 = 14.04±1.95 μg/ml). Thai medicinal plants had anti-inflammatory activity and could inhibit destruction of articular cartilage that corresponded to the traditional medicine and supported using these medicinal plants for OA treatment.

  16. Studies on the hemolytic activity of tentacle extracts of jellyfish Rhopilema esculentum Kishinouye: application of orthogonal test.

    Science.gov (United States)

    Yu, Huahua; Xing, Ronge; Liu, Song; Li, Cuiping; Guo, Zhanyong; Li, Pengcheng

    2007-02-20

    The present work is first reporting the hemolytic activity of venom from jellyfish Rhopilema esculentum Kishinouye extracted by different phosphate buffer solutions and incubated at different temperature according to the orthogonal test L6(1) x 3(6). Of the seven controllable independent variables, incubated temperature and phenylmethylsulfonyl fluoride (PMSF) had strongest effect on the hemolytic activity.

  17. Selective Small Molecule Activators of TREK-2 Channels Stimulate Dorsal Root Ganglion c-Fiber Nociceptor Two-Pore-Domain Potassium Channel Currents and Limit Calcium Influx.

    Science.gov (United States)

    Dadi, Prasanna K; Vierra, Nicholas C; Days, Emily; Dickerson, Matthew T; Vinson, Paige N; Weaver, C David; Jacobson, David A

    2017-03-15

    The two-pore-domain potassium (K2P) channel TREK-2 serves to modulate plasma membrane potential in dorsal root ganglia c-fiber nociceptors, which tunes electrical excitability and nociception. Thus, TREK-2 channels are considered a potential therapeutic target for treating pain; however, there are currently no selective pharmacological tools for TREK-2 channels. Here we report the identification of the first TREK-2 selective activators using a high-throughput fluorescence-based thallium (Tl + ) flux screen (HTS). An initial pilot screen with a bioactive lipid library identified 11-deoxy prostaglandin F2α as a potent activator of TREK-2 channels (EC 50 ≈ 0.294 μM), which was utilized to optimize the TREK-2 Tl + flux assay (Z' = 0.752). A HTS was then performed with 76 575 structurally diverse small molecules. Many small molecules that selectively activate TREK-2 were discovered. As these molecules were able to activate single TREK-2 channels in excised membrane patches, they are likely direct TREK-2 activators. Furthermore, TREK-2 activators reduced primary dorsal root ganglion (DRG) c-fiber Ca 2+ influx. Interestingly, some of the selective TREK-2 activators such as 11-deoxy prostaglandin F2α were found to inhibit the K2P channel TREK-1. Utilizing chimeric channels containing portions of TREK-1 and TREK-2, the region of the TREK channels that allows for either small molecule activation or inhibition was identified. This region lies within the second pore domain containing extracellular loop and is predicted to play an important role in modulating TREK channel activity. Moreover, the selective TREK-2 activators identified in this HTS provide important tools for assessing human TREK-2 channel function and investigating their therapeutic potential for treating chronic pain.

  18. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  19. Polyphenolic content and antioxidant activity of an extractive fraction from Abies alba bark.

    Science.gov (United States)

    Vasincu, Al; Creţu, Elena; Geangalău, Ioana; Amalinei, Roxana Laura Mihăilescu; Miron, Anca

    2013-01-01

    The wood of mature Abies alba Mill. (silver fir) trees is used in construction and furniture industries, the bark being the main waste product. This study aimed to investigate possible therapeutic applications of Abies alba bark waste. A raw extract and four extractive fractions were obtained from silver fir bark. They were also studied regarding their polyphenolic content (Folin-Ciocalteu assay). The ethyl acetate extractive fraction was further studied regarding its ability to scavenge free radicals (DPPH, superoxide anion and hydroxyl radicals) and to chelate ferrous ions. The ethyl acetate fraction contained the highest amount of polyphenols (47.72 +/- 0.38 g gallic acid equivalents/100 g). Its DPPH scavenging and ferrous ions chelating abilities (EC50 = 7.9 +/- 0.1 and 1.56 +/- 0.05 microg/ml) were comparable to those of the positive controls, catechin (EC50 = 7.10 +/- 0.05 microg/ml) and EDTA-Na2 (EC50 = 1.27 +/- 0.01 microg/ml), respectively. It also scavenged superoxide anion and hydroxyl radicals with EC50 values of 53.30 +/- 5.91 and 63.12 +/- 1.78 microg/ml, respectively. The ability of the ethyl acetate fraction to scavenge free radicals and chelate ferrous ions justifies further studies on the possible therapeutic applications of its antioxidant potential.

  20. Antidiarrheal Activity of Aqueous Extract of the Stem Bark of Sapium ...

    African Journals Online (AJOL)

    AESE, in a concentration-dependent manner, reduced the tone and amplitude of spontaneous contractions of the ileal smooth muscle with EC50 of 33.29 and 45.43 μg/ml, respectively. None of the doses used in acute toxicity test induced any significant behavioral changes or mortality. Conclusion: These results suggest ...

  1. A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity.

    Science.gov (United States)

    Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2018-04-27

    Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impairs cognitive function, induces behavioral convulsions, and results in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427 and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at theorthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

  2. Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the chemical space of a less explored "hydrophobic channel".

    Science.gov (United States)

    Zhou, Zhongxia; Liu, Tao; Kang, Dongwei; Huo, Zhipeng; Wu, Gaochan; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong

    2018-02-07

    A new series of diarylpyrimidines (DAPYs) were designed, synthesized and evaluated as novel HIV-1 NNRTIs to further explore the chemical space surrounding the "hydrophobic channel" of the NNRTI binding pocket (NNIBP), guided by the comprehensive analysis of X-ray structural biology data of HIV-1 RT/NNRTI complexes and molecular modeling. Encouragingly, most of the synthesized DAPYs were found to be active against the HIV-1 wild-type (WT) strain with EC 50 values ranging from 3 nM to 63 nM, and displayed significantly reduced cytotoxicity compared with etravirine (ETV) and rilpivirine (RPV). Among them, two most promising compounds Z10 (EC 50 = 3 nM) and Z13 (EC 50 = 3 nM) showed equivalent potency against the HIV-1 WT strain to the reference drugs efavirenz (EFV, EC 50 = 3 nM) and ETV (EC 50 = 3 nM). Notably, Z13 also showed the most potent activity against HIV-1 mutant strains including K103N (EC 50 = 10 nM), E138K (EC 50 = 22 nM) and RES056 (EC 50 = 0.935 μM). Against mutant strains Y181C, Y188L and F227L + V106A, Z17 showed double-digit nanomolar inhibitory activity with EC 50 values 27 nM, 98 nM and 30 nM, respectively. The structure-activity relationships (SARs) and molecular docking studies provided important clues for further molecular elaboration. Collectively, this study provides useful information to guide lead optimization and drug discovery via the exploration of this seldom investigated region.

  3. Prolactin potentiates the activity of acid-sensing ion channels in female rat primary sensory neurons.

    Science.gov (United States)

    Liu, Ting-Ting; Qu, Zu-Wei; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Hu, Wang-Ping

    2016-04-01

    Prolactin (PRL) is a polypeptide hormone produced and released from the pituitary and extrapituitary tissues. It regulates activity of nociceptors and causes hyperalgesia in pain conditions, but little is known the molecular mechanism. We report here that PRL can exert a potentiating effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRL dose-dependently increased the amplitude of ASIC currents with an EC50 of (5.89 ± 0.28) × 10(-8) M. PRL potentiation of ASIC currents was also pH dependent. Second, PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRL receptor antagonist, and removed by intracellular dialysis of either protein kinase C inhibitor GF109203X, protein interacting with C-kinase 1(PICK1) inhibitor FSC-231, or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Four, PRL exacerbated nociceptive responses to injection of acetic acid in female rats. Finally, PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behavior in intact female rats than OVX female and male rats and thus modulation of PRL may be gender-dependent. These results suggest that PRL up-regulates the activity of ASICs and enhances ASIC mediated nociceptive responses in female rats, which reveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Antioxidant activity of methanolic extracts from three coriander (Coriandrum sativum L. fruit varieties

    Directory of Open Access Journals (Sweden)

    Kamel Msaada

    2017-05-01

    Full Text Available In this study, fruit methanolic extract of three coriander (Coriandrum sativum L. varieties (Tunisian, Syrian and Egyptian was assayed for their antioxidant activities. Obtained results showed that there are significant (P < 0.05 variations in total polyphenols (0.94 ± 0.05–1.09 ± 0.02 mg GAE/g DW, total flavonoids (2.03 ± 0.04–2.51 ± 0.08 mg EC/g DW and total condensed tannin (0.09 ± 0.01–0.17 ± 0.01 mg EC/g DW contents. The RP-HPLC analysis revealed the identification of phenolics in coriander fruits with chlorogenic and gallic acids as main compounds in Tunisian, Syrian and Egyptian varieties, respectively. Moreover, fruit methanolic extracts exhibited remarkable DPPH radical scavenging activity with IC50 values ranged from 27.00 ± 6.57 to 36.00 ± 3.22 μg/mL. EC50 values of reducing power activity varied significantly (P < 0.05 from 54.20 ± 6.22 to 122.01 ± 13.25 μg/mL. The IC50 values of β-carotene bleaching assay were between 160.00 ± 18.63 and 240.00 ± 26.35 μg/mL. Our results indicated that coriander fruit might constitute a rich and novel source of natural antioxidants and may be suggested as a new potential source of natural antioxidant and could be used as food additive.

  5. Phytochemical analysis and antioxidant activity of Lycium barbarum (Goji) cultivated in Greece.

    Science.gov (United States)

    Benchennouf, Amina; Grigorakis, Spyros; Loupassaki, Sofia; Kokkalou, Eugene

    2017-12-01

    The fruit of Lycium barbarum L. (Solanaceae), known as goji berry, has been exploited for a long time in traditional Chinese medicine. In recent decades, it has received much attention as one of the trendiest functional foods with a wide array of pharmacological activities in Western diets. In this study the phenolic profile and potential antioxidant capacity of Lycium barbarum cultivated in Crete (Greece) were investigated. The berries were defatted with hexane and then extracted with dichloromethane and methanol using a Soxhlet apparatus. Furthermore, the methanol extract was fractionated with ethyl acetate and butanol. All fractions/extracts were tested for their antioxidant activity (DPPH, FRAP, chemiluminescence). Folin-Ciocalteu and LC-DAD-MS analyses were utilized for the identification of the phenolic compounds. The total phenolic content ranged from 14.13 ± 0.40 (water fraction) to 109.72 ± 4.09 (ethyl acetate fraction) mg gallic acid equivalent/g dry extract. Ethyl acetate extract exhibited the highest scavenging activities determined as EC 50 (4.73 ± 0.20 mg/mL) and IC 50 (0.47 ± 0.001 mg/mL) using DPPH and chemiluminescence assays. Seventeen phenolic compounds, including cinnamoylquinic acids and derivatives, hydrocinnamic acids and flavonoid derivatives, were tentatively identified. To the best of our knowledge, quercetin 3-O-hexose coumaric ester and quercetin 3-O-hexose-O-hexose-O-rhamnose are reported for the first time in goji berry fruits. The results of this study suggest that consumption of goji berry fruits could serve as a potential source of natural antioxidant compounds and that goji berry phenolic extracts could be exploited for nutritional pharmaceutical purposes.

  6. Pharmacodynamic Evaluation of the Activities of Six Parenteral Vancomycin Products Available in the United States

    Science.gov (United States)

    Boyne, Michael T.; Patel, Vikram; Huntley, Clayton; Liu, Weiguo; Fikes, Steven; Kurhanewicz, Stephanie; Rodriquez, Jaime; Robbins, Nichole; Brown, David; Baluya, Dodge; Drusano, G. L.

    2014-01-01

    A recent report found that generic parenteral vancomycin products may not have in vivo efficacies equivalent to those of the innovator in a neutropenic murine thigh infection model despite having similar in vitro microbiological activities and murine serum pharmacokinetics. We compared the in vitro and in vivo activities of six of the parenteral vancomycin products available in the United States. The in vitro assessments for the potencies of the vancomycin products included MIC/minimal bactericidal concentration (MBC) determinations, quantifying the impact of human and murine serum on the MIC values, and time-kill studies. Also, the potencies of the vancomycin products were quantified with a biological assay, and the human and mouse serum protein binding rates for the vancomycin products were measured. The in vivo studies included dose-ranging experiments with the 6 vancomycin products for three isolates of Staphylococcus aureus in a neutropenic mouse thigh infection model. The pharmacokinetics of the vancomycin products were assessed in infected mice by population pharmacokinetic modeling. No differences were seen across the vancomycin products with regard to any in vitro evaluation. Inhibitory sigmoid maximal bacterial kill (Emax) modeling of the relationship between vancomycin dosage and the killing of the bacteria in mice in vivo yielded similar Emax and EC50 (drug exposure driving one-half Emax) values for bacterial killing. Further, there were no differences in the pharmacokinetic clearances of the 6 vancomycin products from infected mice. There were no important pharmacodynamic differences in the in vitro or in vivo activities among the six vancomycin products evaluated. PMID:25385113

  7. Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7.

    Directory of Open Access Journals (Sweden)

    Yaoqing Chen

    Full Text Available For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1. In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC(50 value of 2.76 µg/ml (1.65 µM and showed low cytotoxicity to host cells with a selective index (SI of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1.

  8. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide.

    Science.gov (United States)

    Tilmanis, Danielle; van Baalen, Carel; Oh, Ding Yuan; Rossignol, Jean-Francois; Hurt, Aeron C

    2017-11-01

    Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor-resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC 50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Analogues of morphanthridine and the tear gas dibenz[b,f][1,4]oxazepine (CR) as extremely potent activators of the human transient receptor potential ankyrin 1 (TRPA1) channel.

    Science.gov (United States)

    Gijsen, Harrie J M; Berthelot, Didier; Zaja, Mirko; Brône, Bert; Geuens, Ivo; Mercken, Marc

    2010-10-14

    The TRPA1 channel can be considered as a key biological sensor to irritant chemicals. In this paper, the discovery of 11H-dibenz[b,e]azepines (morphanthridines) and dibenz[b,f][1,4]oxazepines is described as extremely potent agonists of the TRPA1 receptor. This has led to the discovery that most of the known tear gases are potent TRPA1 activators. The synthesis and biological activity of a number of substituted morphanthridines and dibenz[b,f][1,4]oxazepines have given insight into the SAR around this class of TRPA1 agonists, with EC(50) values ranging from 1 μM to 0.1 nM. Compounds 6 and 32 can be considered as the most potent TRPA1 agonists known to date, with 6 now being used successfully as a screening tool in the discovery of TRPA1 antagonists. The use of ligands such as 6 and 32 as pharmacological tools may contribute to the basic knowledge of the TRPA1 channel and advance the development of TRPA1 antagonists as potential treatment for conditions involving TRPA1 activation, including asthma and pain.

  10. DB-02, a C-6-cyclohexylmethyl substituted pyrimidinone HIV-1 reverse transcriptase inhibitor with nanomolar activity, displays an improved sensitivity against K103N or Y181C than S-DABOs.

    Directory of Open Access Journals (Sweden)

    Xing-Jie Zhang

    Full Text Available 6-(cyclohexylmethyl-5-ethyl-2-((2-oxo-2-phenylethylthiopyrimidin-4(3H-one (DB-02 is a member of the newly reported synthetic anti-HIV-1 compounds dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines, S-DACOs. In vitro anti-HIV-1 activity and resistance profile studies have suggested that DB-02 has very low cytotoxicity (CC50>1mM to cell lines and peripheral blood mononuclear cells (PBMCs. It displays potent anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (EC50s range from 2.40 to 41.8 nM. Studies on site-directed mutagenesis, genotypic resistance profiles revealed that V106A was the major resistance contributor for the compound. Molecular docking analysis showed that DB-02 located in the hydrophobic pocket with interactions of Lys101, Val106, Leu234, His235. DB-02 also showed non-antagonistic effects to four approved antiretroviral drugs. All studies indicated that DB-02 would be a potential NNRTI with low cytotoxicity and improved activity.

  11. In Vivo Anti-inflammatory and Antinociceptive Activities of Extracts of ...

    African Journals Online (AJOL)

    It was observed that the 80% methanol extracts of both plants could significantly lower carrageenan-induced paw oedema at doses of 200 mg/kg, p.o. Among the solvent fractions, the acetone, chloroform and methanol fractions of S. nilotica exhibited anti-inflammatory activity, the strongest being that of the acetone fraction.

  12. Purification, crystallization and preliminary X-ray diffraction analysis of an acidic phospholipase A2 with vasoconstrictor activity from Agkistrodon halys pallas venom

    International Nuclear Information System (INIS)

    Zou, Zhisong; Zeng, Fuxing; Zhang, Lu; Niu, Liwen; Teng, Maikun; Li, Xu

    2012-01-01

    A vasoconstrictor PLA 2 was purified from Agkistrodon halys pallas venom and the preliminary X-ray diffraction analysis had been described. Phospholipases A 2 (PLA 2 s) are the major component of snake venoms and exert a variety of relevant toxic actions such as neurotoxicity and myotoxicity, amongst others. An acidic PLA 2 , here named AhV-aPA, was purified from Agkistrodon halys pallas venom by means of a three-step chromatographic procedure. AhV-aPA migrated as a single band on SDS–PAGE gels, with a molecular weight of about 14 kDa. Like other acidic aPLA 2 s, AhV-aPA has high enzymatic activity. Tension measurements of mouse thoracic aortic rings remarkably indicated that AhV-aPA could induce a further contractile response on the 60 mM K + -induced contraction, with an EC 50 of 369 nmol l −1 . Rod-shaped crystals were obtained by the hanging-drop vapour-diffusion method and diffracted to a resolution limit of 2.30 Å. The crystals belonged to space group P222, with unit-cell parameters a = 44.27, b = 68.39, c = 81.54 Å

  13. Chemical and ecotoxicological analyses of sediments and elutriates of contaminated rivers due to e-waste recycling activities using a diverse battery of bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Wang, F.; Leung, A.O.W.; Wu, S.C.; Yang, M.S. [Croucher Institute for Environmental Sciences, and Department of Biology, Hong Kong Baptist University, Kowloon Tong (Hong Kong); Wong, M.H., E-mail: mhwong@hkbu.edu.h [Croucher Institute for Environmental Sciences, and Department of Biology, Hong Kong Baptist University, Kowloon Tong (Hong Kong)

    2009-07-15

    A multi-trophic, multi-exposure phase assessment approach was applied to characterize the toxicity of sediments collected from two rivers in Guiyu, China, an e-waste recycling centre. Elutriate toxicity tests (bacterium Vibrio fischeri and microalga Selenastrum capricornutum) and whole sediment toxicity test (crustacean Heterocypris incongruens) showed that most sediments exhibited acute toxicity, due to elevated heavy metals and PAHs levels, and low pH caused by uncontrolled acid discharge. The survival rates of crustaceans were negatively (p < 0.05) correlated with total PAHs in sediments (411-1755 mg kg{sup -1}); EC50s of V. fischeri on the elutriates were significantly correlated with elutriate pH (p < 0.01). Significant (p < 0.05) correlations between the induction of hepatic metallothionein in tilapia (Oreochromis mossambicus) and metal concentrations (Cu, Zn, Pb) in sediments were also observed, when fish were fed with diets containing sediment. The results showed that uncontrolled e-waste recycling activities may bring adverse effects to local aquatic ecosystem. - Toxicity tests using different trophic organisms provided important information, supplementing chemical analyses.

  14. Sri Lankan black tea (Camellia sinensis L. inhibits the methylglyoxal mediated protein glycation and potentiates its reversing activity in vitro

    Directory of Open Access Journals (Sweden)

    Walimuni Kanchana Subhashini Mendis Abeysekera

    2016-02-01

    Full Text Available Objective: To evaluate inhibitory activity of methylglyoxal (MGO mediated protein glycation and ability to potentiate its reversing activity and range of antioxidant properties of Sri Lankan low grown orthodox orange pekoe grade black tea. Methods: Freeze dried black tea brew (BTB was used as the sample in this study. Antiglycation and glycation reversing activity was studied in bovine serum albumin (BSA-MGO model. Antioxidant properties were studied using total polyphenolic content, total flavonoid content, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, 1,1-diphenyl-2-picrylhydrazine and ferric reducing antioxidant power in vitro antioxidant assays. Results: The results demonstrated significant (P < 0.05 and dose dependant inhibition of BSA-MGO glycation [IC50: (164.30 ± 4.85 µg/mL], potentiating of its reversing activity [EC50: (235.39 ± 5.37 µg/mL] and marked antioxidant properties [total polyphenolic content: (119.55 ± 9.97 mg gallic acid equivalents/g BTB; total flavonoid content: (6.04 ± 1.26 mg quercetin equivalents/g BTB; 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, 1,1-diphenyl-2- picrylhydrazine and ferric reducing antioxidant power: (3.29 ± 0.06, (1.95 ± 0.15 and (1.31 ± 0.19 mmol Trolox equivalents/g BTB, respectively]. No correlations were observed between antioxidant activity and BSA-MGO glycation. Conclusions: The novel properties observed for Sri Lankan orange pekoe grade black tea indicate its usefulness as a supplementary beverage in managing MGO and advanced glycation end products related diseases and ailments.

  15. Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds.

    Science.gov (United States)

    Wiemann, Jana; Heller, Lucie; Perl, Vincent; Kluge, Ralph; Ströhl, Dieter; Csuk, René

    2015-12-01

    The betulinic acid-derived hydroxamates 5-18, the amides 19-24, and betulin-derived bis-carbamates 25-28 as well as the carbamates 31-40 and 44-48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3-O-acetyl hydroxamic acid 5 EC