Structure-activity relationships of bumetanide derivatives

DEFF Research Database (Denmark)

Pedersen, Kasper Lykke; Töllner, Kathrin; Römermann, Kerstin

2015-01-01

of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. EXPERIMENTAL APPROACH: In this study......, the effect of a series of diuretically active bumetanide derivatives was investigated on human NKCC2 variant A (hNKCC2A) expressed in Xenopus laevis oocytes. KEY RESULTS: Bumetanide blocked hNKCC2A transport with an IC50 of 4 μM. There was good correlation between the diuretic potency of bumetanide and its...... of the structural requirements that determine relative potency of loop diuretics on human NKCC2 splice variants, and may lead to the discovery of novel high-ceiling diuretics....

New uracil derivatives and their biological activity

International Nuclear Information System (INIS)

Hudecova, D.; Striganova, J.; Chovanec, P.; Uher, M.

1998-01-01

Present study is concentrated to the research of antimicrobial activity of some derivatives of the uracil and 1,3-dimethyluracyl. The antimicrobial effects of these compounds have been tested on various strains of bacteria, yeasts, and filamentous fungi. The highest antimicrobial effects were found with dithiocarbamato-derivatives, which were effective against pathogenic and non-pathogenic bacteria (IC 50 = 7-25 μg cm -3 ), yeasts (IC 50 = 9-60 μg cm -3 ) and filamentous fungi.The most sensitive fungus to dithiocarbamato-derivatives was Botritis cinerea. It seems to be apparent that the presence of the -NH-C(S)-S- group in molecules of derivatives of uracil and and 1,3-dimethyluracyl influencing the incorporation rate [ 14 ]-adenine and 14 ]-leucine into the biomolecules and also markedly inhibits oxygen consumption (IC 50 = 58 μg cm -3 ). The same derivative demonstrated no mutagenic activity. (authors)

A fully resolved active musculo-mechanical model for esophageal transport

Science.gov (United States)

Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

2015-10-01

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

Science.gov (United States)

Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

2015-01-01

The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

A fully resolved fluid-structure-muscle-activation model for esophageal transport

Science.gov (United States)

Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

2013-11-01

Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

Microwave Synthesis, Characterization, and Antimicrobial Activity of Some Novel Isatin Derivatives

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Ayman El-Faham

2015-01-01

Full Text Available Three series of isatin derivatives [3-hydrazino, 3-thiosemicarbazino, and 3-imino carboxylic acid derivatives] were synthesized employing microwave irradiation. The prepared compounds were characterized by FT-IR, NMR, elemental analysis, and X-ray crystallography for derivatives 5b. The synthesized compounds were screened for antimicrobial activity against selected bacteria and fungi. The results revealed that the N-alkyl isatin derivatives were biologically active with different spectrums activity. Most of the 3-hydrazino and 3-thiosemicarbazino isatin derivatives were biologically inactive and generally the active derivatives showed weak to moderate activity mainly against Gram-positive bacteria. The imino isatin carboxylic acid derivatives (2-[4-(1-benzyl-5-bromo-2-oxoindolin-3-ylideneamino phenyl]acetic acid, 5d showed promising activity against all tested Gram-positive bacteria and against fungal pathogens.

5-Nitroimidazole Derivatives and their Antimicrobial Activity

International Nuclear Information System (INIS)

Khan, K.M.; Salar, U.; Yousuf, S.; Naz, F.

2016-01-01

5-Nitroimidazole derivatives 2-8 were synthesized from secnidazole. The syntheses were accomplished in two steps which start from the oxidation of secnidazole to the secnidazolone 1. Secnidazolone 1 was converted into its hydrazone derivative 2-8 by treating with different substituted acid hydrazide. Compounds 2-8 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, compounds 3 and 4 showed the significant activity against Staphylococcus epidermidis, however, compound 2 showed good inhibitions against Corynebacterium diphtheria when compared with the standard. Compound 3 showed good inhibitory potential against tested Gram-negative bacterial strains i.e. Enterobacter aerogene, Escherichia coli, Salmonella typhi, Salmonella paratyphi A, Shigella flexeneri and Vibrio choleriae. All synthetic derivatives were also tested against eight fungal stains, however, they were weekly active against Aspergillus flavus and Candida albican. The synthesized compounds were characterized by different spectroscopy techniques. (author)

Anticancer activities of bovine and human lactoferricin-derived peptides.

Science.gov (United States)

Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

2017-02-01

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

Mexico; Financial Sector Assessment Program Update: Technical Note: Derivatives Market: Overview and Potential Vulnerabilities

OpenAIRE

International Monetary Fund

2007-01-01

This technical note provides an overview of Mexico’s derivatives markets, and describes concisely the derivatives regulatory framework and risk management practices in financial institutions active in these markets. The most important derivatives market in Mexico is the over-the-counter (OTC) derivatives market, which is fully integrated with the global derivatives market. The origin of the OTC derivatives market can be traced back to the 1994 Mexican crisis that forced Mexico to abandon its ...

The effect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling

Science.gov (United States)

Sulistyo, Bambang

2016-11-01

The research was aimed at studying the efect of choosing three different C factor formulae derived from NDVI on a fully raster-based erosion modelling of The USLE using remote sensing data and GIS technique. Methods applied was by analysing all factors affecting erosion such that all data were in the form of raster. Those data were R, K, LS, C and P factors. Monthly R factor was evaluated based on formula developed by Abdurachman. K factor was determined using modified formula used by Ministry of Forestry based on soil samples taken in the field. LS factor was derived from Digital Elevation Model. Three C factors used were all derived from NDVI and developed by Suriyaprasit (non-linear) and by Sulistyo (linear and non-linear). P factor was derived from the combination between slope data and landcover classification interpreted from Landsat 7 ETM+. Another analysis was the creation of map of Bulk Density used to convert erosion unit. To know the model accuracy, model validation was done by applying statistical analysis and by comparing Emodel with Eactual. A threshold value of ≥ 0.80 or ≥ 80% was chosen to justify. The research result showed that all Emodel using three formulae of C factors have coeeficient of correlation value of > 0.8. The results of analysis of variance showed that there was significantly difference between Emodel and Eactual when using C factor formula developed by Suriyaprasit and Sulistyo (non-linear). Among the three formulae, only Emodel using C factor formula developed by Sulistyo (linear) reached the accuracy of 81.13% while the other only 56.02% as developed by Sulistyo (nonlinear) and 4.70% as developed by Suriyaprasit, respectively.

New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

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Branka Zorc

2012-01-01

Full Text Available Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1, 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethylphenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1. Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

FPGA-based fully digital fast power switch fault detection and compensation for three-phase shunt active filters

Energy Technology Data Exchange (ETDEWEB)

Karimi, S.; Saadate, S. [Groupe de Recherche en Electrotechnique et Electronique de Nancy, GREEN-UHP, CNRS UMR 7037 (France); Poure, P. [Laboratoire d' Instrumentation Electronique de Nancy, LIEN, EA 3440, France Nancy Universite - Universite Henri Poincare de Nancy I, BP 239, 54506 Vandoeuvre les Nancy cedex (France)

2008-11-15

This paper discusses the design, implementation, experimental validation and performances of a fully digital fast power switch fault detection and compensation for three-phase shunt active power filters. The approach introduced in this paper minimizes the time interval between the fault occurrence and its diagnosis. This paper demonstrates the possibility to detect a faulty switch of the active filter in less than 10 {mu}s by using simultaneously a ''time criterion'' and a ''voltage criterion''. In order to attain this fast detection time a FPGA (Field Programmable Gate Array) is used. The other feature introduced in this approach is that the control scheme used to compensate the current load harmonics and fault tolerant scheme are both programmed in only one FPGA. ''FPGA in the loop'' prototyping results and fully experimental results based on a real active power filter verify satisfactory performances of the proposed method. (author)

Anticancer activities of bovine and human lactoferricin-derived peptides

NARCIS (Netherlands)

Arias, M.; Hilchie, A.L.; Haney, E.F.; Bolscher, J.G.M.; Hyndman, M.E.; Hancock, R.E.W.; Vogel, H.J.

2017-01-01

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits

Engineering Escherichia coli Nicotinic Acid Mononucleotide Adenylyltransferase for Fully Active Amidated NAD Biosynthesis.

Science.gov (United States)

Wang, Xueying; Zhou, Yongjin J; Wang, Lei; Liu, Wujun; Liu, Yuxue; Peng, Chang; Zhao, Zongbao K

2017-07-01

NAD and its reduced form NADH function as essential redox cofactors and have major roles in determining cellular metabolic features. NAD can be synthesized through the deamidated and amidated pathways, for which the key reaction involves adenylylation of nicotinic acid mononucleotide (NaMN) and nicotinamide mononucleotide (NMN), respectively. In Escherichia coli , NAD de novo biosynthesis depends on the protein NadD-catalyzed adenylylation of NaMN to nicotinic acid adenine dinucleotide (NaAD), followed by NAD synthase-catalyzed amidation. In this study, we engineered NadD to favor NMN for improved amidated pathway activity. We designed NadD mutant libraries, screened by a malic enzyme-coupled colorimetric assay, and identified two variants, 11B4 (Y84V/Y118D) and 16D8 (A86W/Y118N), with a high preference for NMN. Whereas in the presence of NMN both variants were capable of enabling the viability of cells of E. coli BW25113-derived NAD-auxotrophic strain YJE003, for which the last step of the deamidated pathway is blocked, the 16D8 expression strain could grow without exogenous NMN and accumulated a higher cellular NAD(H) level than BW25113 in the stationary phase. These mutants established fully active amidated NAD biosynthesis and offered a new opportunity to manipulate NAD metabolism for biocatalysis and metabolic engineering. IMPORTANCE Adenylylation of nicotinic acid mononucleotide (NaMN) and adenylylation of nicotinamide mononucleotide (NMN), respectively, are the key steps in the deamidated and amidated pathways for NAD biosynthesis. In most organisms, canonical NAD biosynthesis follows the deamidated pathway. Here we engineered Escherichia coli NaMN adenylyltransferase to favor NMN and expressed the mutant enzyme in an NAD-auxotrophic E. coli strain that has the last step of the deamidated pathway blocked. The engineered strain survived in M9 medium, which indicated the implementation of a functional amidated pathway for NAD biosynthesis. These results enrich

INVESTIGATION OF ANTIFUNGAL ACTIVITY OF QUINOLINIUM DERIVATIVES

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G. A. Alexandrova

2013-01-01

Full Text Available Abstract. Antifungal activity (Candida albicans, Candida krusei of some substituted quinolinium derivatives has been investigated. It was established that the most perspective compound for detail investigation of antifungal activity by labeled biomarkers method was N-phenylbenzoquinaldinium tetrafluoroborate.

Design, Synthesis and Insecticidal Activity of Novel Phenylurea Derivatives

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Jialong Sun

2015-03-01

Full Text Available A series of novel phenylurea derivatives were designed and synthesized according to the method of active groups linkage and the principle of aromatic groups bioisosterism in this study. The structures of the novel phenylurea derivatives were confirmed based on ESI-MS, IR and 1H-NMR spectral data. All of the compounds were evaluated for the insecticidal activity against the third instars larvae of Spodoptera exigua Hiibner, Plutella xyllostella Linnaeus, Helicoverpa armigera Hubner and Pieris rapae Linne respectively, at the concentration of 10 mg/L. The results showed that all of the derivatives displayed strong insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, chlorbenzuron and metaflumizone. Among the synthesized compounds, 3b, 3d, 3f, 4b and 4g displayed broad spectrum insecticidal activity.

Comparison tests, in a pilot plant, of the performance of a coal-derived granular activated carbon: a comparison with coconut husk derived activated carbon

Energy Technology Data Exchange (ETDEWEB)

Hirata, S.; Kasahara, A.; Tsuruzono, Y.; Gotoh, M.

1986-01-01

A 160 m/sup 3//d pilot plant has been used in a series of comparison tests of the performance of coal-derived and coconut husk derived activated carbons. Activated carbons are used to remove trihalomethane precursors and malodorous substances from city water. A higher mean removal of coloration and COD/sub M//sub n/ was achieved with the coal-derived carbon (by factors of 1.5 and 1.8, respectively). The two activated carbons gave similar performances as regards turbidity, alkalinity, total iron and total manganese. 4 figures, 5 tables.

Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

Science.gov (United States)

Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

2003-01-01

An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma-derived

Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling.

Science.gov (United States)

Mori, Yoshikazu; Hirokawa, Takatsugu; Aoki, Katsuyuki; Satomi, Hisanori; Takeda, Shuichi; Aburada, Masaki; Miyamoto, Ken-ichi

2008-05-01

We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFbeta R-ligand interactions, is urgently needed. Here we present models of the PDGFbeta R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by alpha-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFbeta R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors.

The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

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Marina Azevedo Souza

2013-05-01

Full Text Available Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively. In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.

Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives

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Yunpeng Yi

2017-06-01

Full Text Available A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR, Infrared Spectroscopy (IR, and High Resolution Mass Spectrometer (HRMS. Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA, methicillin-resistant Staphylococcus epidermidis (MRSE, and vancomycin-resistant Enterococcus (VRE in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, 3a, 3b, and 3f, displayed modest antibacterial activities. Compound 3a, the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of tiamulin fumarate. Moreover, molecular docking studies of 3a and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives.

Natural Cinnamic Acids, Synthetic Derivatives and Hybrids with Antimicrobial Activity

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Juan David Guzman

2014-11-01

Full Text Available Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

Synthesis and Fungicidal Activity of β-Carboline Alkaloids and Their Derivatives

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Zhibin Li

2015-07-01

Full Text Available A series of β-Carboline derivatives were designed, synthesized, and evaluated for their fungicidal activities in this study. Several derivatives electively exhibited fungicidal activities against some fungi. Especially, compound F5 exhibited higher fungicidal activity against Rhizoctonia solani (53.35% than commercial antiviral agent validamycin (36.4%; compound F16 exhibited high fungicidal activity against Oospora citriaurantii ex Persoon (43.28%. Some of the alkaloids and their derivatives (compounds F4 and F25 exhibited broad-spectrum fungicidal activity. Specifically, compound F4 exhibited excellent high broad-spectrum fungicidal activity in vitro, and the curative and protection activities against P. litchi in vivo reached 92.59% and 59.26%, respectively. The new derivative, F4, with optimized physicochemical properties, obviously exhibited higher activities both in vitro and in vivo; therefore, F4 may be used as a new lead structure for the development of fungicidal drugs.

Mechanism of salt-induced activity enhancement of a marine-derived laccase, Lac15.

Science.gov (United States)

Li, Jie; Xie, Yanan; Wang, Rui; Fang, Zemin; Fang, Wei; Zhang, Xuecheng; Xiao, Yazhong

2018-04-01

Laccase (benzenediol: oxygen oxidoreductases, EC1.10.3.2) is a multi-copper oxidase capable of oxidizing a variety of phenolic and other aromatic organic compounds. The catalytic power of laccase makes it an attractive candidate for potential applications in many areas of industry including biodegradation of organic pollutants and synthesis of novel drugs. Most laccases are vulnerable to high salt and have limited applications. However, some laccases are not only tolerant to but also activated by certain concentrations of salt and thus have great application potential. The mechanisms of salt-induced activity enhancement of laccases are unclear as yet. In this study, we used dynamic light scattering, size exclusion chromatography, analytical ultracentrifugation, intrinsic fluorescence emission, circular dichroism, ultraviolet-visible light absorption, and an enzymatic assay to investigate the potential correlation between the structure and activity of the marine-derived laccase, Lac15, whose activity is promoted by low concentrations of NaCl. The results showed that low concentrations of NaCl exert little influence on the protein structure, which was partially folded in the absence of the salt; moreover, the partially folded rather than the fully folded state seemed to be favorable for enzyme activity, and this partially folded state was distinctive from the so-called 'molten globule' occasionally observed in active enzymes. More data indicated that salt might promote laccase activity through mechanisms involving perturbation of specific local sites rather than a change in global structure. Potential binding sites for chloride ions and their roles in enzyme activity promotion are proposed.

Platelet-derived growth factor inhibits platelet activation in heparinized whole blood.

Science.gov (United States)

Selheim, F; Holmsen, H; Vassbotn, F S

1999-08-15

We previously have demonstrated that human platelets have functionally active platelet-derived growth factor alpha-receptors. Studies with gel-filtered platelets showed that an autocrine inhibition pathway is transduced through this tyrosine kinase receptor during platelet activation. The physiological significance of this inhibitory effect of platelet-derived growth factor on gel-filtered platelets activation is, however, not known. In the present study, we investigated whether platelet-derived growth factor inhibits platelet activation under more physiological conditions in heparinized whole blood, which represents a more physiological condition than gel-filtered platelets. Using flow cytometric assays, we demonstrate here that platelet-derived growth factor inhibits thrombin-, thrombin receptor agonist peptide SFLLRN-, and collagen-induced platelet aggregation and shedding of platelet-derived microparticles from the platelet plasma membrane during platelet aggregation in stirred heparinized whole blood. The inhibitory effect of platelet-derived growth factor was dose dependent. However, under nonaggregating conditions (no stirring), we could not demonstrate any significant effect of platelet-derived growth factor on thrombin- and thrombin receptor agonist peptide-induced platelet surface expression of P-selectin. Our results demonstrate that platelet-derived growth factor appears to be a true antithrombotic agent only under aggregating conditions in heparinized whole blood.

Insecticidal and Nematicidal Activities of Novel Mimosine Derivatives

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Binh Cao Quan Nguyen

2015-09-01

Full Text Available Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal and nematicidal activities of novel mimosine derivatives. Interestingly, mimosinol and deuterated mimosinol (D-mimosinol from mimosine had strong insecticidal activity which could be a result of tyrosinase inhibition (IC50 = 31.4 and 46.1 μM, respectively. Of synthesized phosphoramidothionate derivatives from two these amino alcohols, two compounds (1a and 1b showed high insecticidal activity (LD50 = 0.5 and 0.7 μg/insect, respectively with 50%–60% mortality at 50 μg/mL which may be attributed to acetylcholinesterase inhibition. Compounds 1a and 1b also had strong nematicidal activity with IC50 = 31.8 and 50.2 μM, respectively. Our results suggest that the length of the alkyl chain and the functional group at the C5-position of phosphoramidothionates derived from mimosinol and d-mimosinol are essential for the insecticidal and nematicidal activities. These results reveal an unexplored scaffold as new insecticide and nematicide.

Synthesis and Insecticidal Activities of New Ester-Derivatives of Celangulin-V

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Wenjun Wu

2011-12-01

Full Text Available In order to develop new biorational pesticides, ten new 6-substituted ester derivatives of Celangulin-V were designed and synthesized. The structures of the new derivatives were confirmed by IR, 1H-NMR, 13C-NMR and ESI-MS spectral analysis. Insecticidal activities of these compounds were tested against the third-instar larvae of Mythimna separata. Two derivatives (1.1, 1.2 showed higher insecticidal activities than Celangulin-V, with mortality of 75.0% and 83.3%, respectively. While four compounds (1.3, 1.4, 1.7, 1.8 denoted lower insecticidal activities, the others (1.5, 1.6, 1.9, 1.10 revealed no activities at a concentration of 10 mg.mL−1. The results suggest that C-6 substitutions of Celangulin-V are very important in determining the insecticidal activities of its ester-derivatives. That the acetyl (1.1 and propionyl (1.2 derivatives possessed much higher insecticidal activities than Celangulin-V itself supported the view that Celangulin-V has the potential to be a lead structure of semi-synthetic green insecticides.

Exploiting Natural Products to Build Metalla-Assemblies: The Anticancer Activity of Embelin-Derived Rh(III and Ir(III Metalla-Rectangles

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Gajendra Gupta

2014-05-01

Full Text Available Six new pentamethylcyclopentadienyl Rh(III and Ir(III metalla-rectangles ([3](CF3SO34–[8](CF3SO34 have been prepared by a self-assembly strategy using the embelin-derived metalla-clips (η5-C5Me52M2(μ4-C6HRO4-κOCl2 (M = Rh, 1; M = Ir, 2; R = (CH210CH3 and the linear ditopic ligands, pyrazine, 4,4'-bipyridine and 1,2-bis (4-pyridylethylene. These new metalla-rectangles have been obtained in high yield and isolated as their triflate salts. The complexes have been fully characterized by standard spectroscopic techniques and the antiproliferative activity of these tetranuclear complexes was evaluated in vitro on cancerous (DU-145, A-549, HeLa and noncancerous (HEK-293 cell lines. The biological study has showed a better activity for the rhodium derivatives over the iridium analogs and for all complexes a very good selectivity for cancerous over noncancerous cells. The presence of lipophilic side chains coupled with the positive charge of the tetranuclear complexes suggested a cytotoxic activity involving the mitochondrial machinery, as demonstrated by multiple biological experiments.

Antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate

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Yoshimi eMatsumoto

2012-02-01

Full Text Available (--Epigallocatechin-3-O-gallate (EGCG has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori, S. et al. (Bioorg Med Chem Lett 18:4249-4252, 2008 found that addition of long acyl chains (C16–18 to EGCG enhanced its anti-influenza virus activity up to 44-fold. The chemical stability of EGCG against oxidative degradation was also enhanced by acylation. We further evaluated the in vitro activity spectrum of the EGCG derivatives against a wide range of bacteria and fungi. A series of EGCG O-acyl derivatives were synthesized by lipase-catalyzed transesterification. These derivatives exhibited several-fold higher activities than EGCG, particularly against Gram-positive organisms. Antifungal activities of the derivatives were also 2 to 4-fold superior to those of EGCG. The activities of the EGCG derivatives against Gram-negative bacteria were not distinguishable from those of EGCG. Among the derivatives evaluated, MICs of dioctanoate, palmitate (C16, palmitoleate, and linolenate for 17 Staphylococcus aureus strains were 4–32 μg/ml, although MIC of EGCG for these 17 strains was >128 μg/ml. C16 demonstrated rapid bactericidal activity against MRSA at 25 μg/ml. The enhanced activity of C16 against S. aureus was supported by its increased membrane permeabilizing activity determined by increased SYTOX Green uptake. The EGCG derivatives were exported by the efflux pump AcrAB-TolC of Escherichia coli. The tolC deletion mutant exhibited higher sensitivity to C16 than to EGCG. Addition of long alkyl chains to EGCG significantly enhanced its activities against various bacteria and fungi, particularly against S. aureus including MRSA. C16 would be an alternative to antibiotics and disinfectants.

Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol

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Emerson Silva Lima

2012-12-01

Full Text Available 4-nerolidylcatechol (4-NC is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast, however 4-NC was more cytotoxic (IC50 = 31.4 µM and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at −20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at −20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds.

A Simple Fully Passive Safety Option for SMART SBLOCA

International Nuclear Information System (INIS)

Lee, Won Jae

2012-01-01

SMART reactor, an integral pressurized water reactor (iPWR), is developed by KAERI and now under standard design licensing review. Integral reactor design of the SMART has small diameter penetrations below 2 inches at upper parts of reactor pressure vessel (RPV) and the core is located at very lower part. Amount of reactor coolant inventory is around 0.55tons/MWth during normal operations, which is seven times more than that of conventional PWRs. Such intrinsic safety features of the SMART can provide prolonged core cooling during a small-break loss-of-coolant accident (SBLOCA). As an engineered safety feature for SBLOCA, electrically two-train and mechanically four-train active safety injection (SI) systems are provided to refill the RPV, whose safety been proven through safety analysis and experiments. In addition, four-train passive residual heat removal systems (PRHRSs) are provided to remove core decay heat by natural circulation in the secondary side of steam generators during transient and accident conditions. After Fukushima disaster, a passive safety of nuclear power plants has become more emphasized than conventional active safety, even though there are still debates whether it can really insure the realistic safety. Passive safety is defined such that the core safety is ensured for 72 hours after accidents without any active safety systems and operator actions. In light of this, a simple fully passive safety option for SBLOCA is proposed: low-pressure safety injection tanks (SITs) and heat pipes submerged in the PRHRS emergency coolant tanks (ECTs). Post-LOCA long-term cooling after 72 hours is provided by sump recirculation using shutdown cooling system. Realistic analysis method using MARS3.1 is used to derive fully passive safety option, and then to screen design and operating parameters and to demonstrate the safety performance of SITs. SI line break is selected as a reference SBLOCA scenario

Allicin and derivates are cysteine protease inhibitors with antiparasitic activity.

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Waag, Thilo; Gelhaus, Christoph; Rath, Jennifer; Stich, August; Leippe, Matthias; Schirmeister, Tanja

2010-09-15

Allicin and derivatives thereof inhibit the CAC1 cysteine proteases falcipain 2, rhodesain, cathepsin B and L in the low micromolar range. The structure-activity relationship revealed that only derivatives with primary carbon atom in vicinity to the thiosulfinate sulfur atom attacked by the active-site Cys residue are active against the target enzymes. Some compounds also show potent antiparasitic activity against Plasmodium falciparum and Trypanosoma brucei brucei. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The antibacterial activity of honey derived from Australian flora.

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Julie Irish

Full Text Available Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57% of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla, jarrah (Eucalyptus marginata and jellybush (Leptospermum polygalifolium. In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8% samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4 °C than at 25 °C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25 °C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted.

Benzoxazole derivatives suppress lipopolysaccharide-induced mast cell activation.

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Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Choo, Hea-Young Park; Lee, Kyung Ho

2018-05-01

Mast cells are central regulators of allergic inflammation that function by releasing various proallergic inflammatory mediators, including histamine, eicosanoids and proinflammatory cytokines. Occasionally, bacterial infections may initiate or worsen allergic inflammation. A number of studies have indicated that activation of lipoxygenase in mast cells positive regulates allergic inflammatory responses by generating leukotrienes and proinflammatory cytokines. In the present study, the effects of benzoxazole derivatives on the lipopolysaccharide (LPS)‑induced expression of proinflammatory cytokines, production of histamine and surface expression of co‑stimulatory molecules on bone marrow-derived mast cells (BMMCs) were studied. The benzoxazole derivatives significantly reduced the expression of interleukin (IL)‑1β, IL‑6, IL‑13, tumor necrosis factor‑α, perilipin (PLIN) 2, and PLIN3 in BMMCs treated with LPS. Furthermore, histamine production was suppressed in BMMCs treated with LPS, or treated with phorbol-12-myristate-13-acetate/ionomycin. Benzoxazole derivatives marginally affected the surface expression of cluster of differentiation (CD)80 and CD86 on BMMCs in the presence of LPS, although LPS alone did not increase the expression of those proteins. Therefore, benzoxazole derivatives inhibited the secretion of proinflammatory cytokines in mast cells and may be potential candidate anti‑allergic agents to suppress mast cell activation.

Synthesis and anticandidal activity of some imidazopyridine derivatives.

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Kaplancikli, Zafer Asim; Turan-Zitouni, Gülhan; Ozdemir, Ahmet; Revial, Gilbert

2008-12-01

New hydrazide derivatives of imidazo[1,2-a]pyridine have been synthesized and evaluated for anticandidal activity. The reaction of imidazo[1,2-a]pyridine-2-carboxylic acid hydrazides with various benzaldehydes gave N-(benzylidene)imidazo[ 1,2-a]pyridine-2-carboxylic acid hydrazide derivatives. Their anticandidal activities against Candida albicans and Candida glabrata (isolates obtained from Osmangazi University, Faculty of Medicine, Eskisehir, Turkey), Candida albicans (ATCC 90028), Candida utilis (NRLL Y-900), Candida tropicalis (NRLL Y-12968), Candida krusei (NRLL Y-7179), Candida zeylanoides (NRLL Y-1774), and Candida parapsilosis (NRLL Y-12696) were investigated.

Factors influencing the antifolate activity of synthetic tea-derived catechins.

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Sáez-Ayala, Magalí; Fernández-Pérez, María Piedad; Chazarra, Soledad; Mchedlishvili, Nani; Tárraga-Tomás, Alberto; Rodríguez-López, José Neptuno

2013-07-16

Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

Antimutagenic activity of dextran gammaphos derivatives

International Nuclear Information System (INIS)

Bakhitova, L.M.; Pashin, O.V.; Drobchenko, S.N.; Bondarev, G.I.

1991-01-01

In experiments with V-79 Chinese hamster cell culture the influence of dextran gammaphos derivatives on the mutagenic effects of γ-radiation was studied by the number of cells with micronuclei and fragmented nuclei. Products of interaction between gammaphos and dialdehyde dextran were shown to a higher antimutagenic activity than gammaphos

Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

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Sumiya, Yu; Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

2015-08-01

Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Central muscle relaxant activities of 2-methyl-3-aminopropiophenone derivatives].

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Kontani, H; Mano, A; Koshiura, R; Yamazaki, M; Shimada, Y; Oshita, M; Morikawa, K; Kato, H; Ito, Y

1987-02-01

In this experiment, we synthetized new 2-methyl-3-aminopropiophenone (MP) derivatives, whose structure is known to have central muscle relaxant activities, and quinolizidine and indan . tetralin derivatives derived from MP by cyclization, and we investigated the central muscle relaxant activity. Among the quinolizidine derivatives, there was a very strong central depressant agent, trans (3H, 9aH)-3-(p-chloro) benzoyl-quinolizidine (HSR-740), and among the indan . tetralin derivatives, there was an excitant agents, trans (1H, 2H)-5-methoxy-3, 3-dimethyl-2-piperidinomethyl indan-1-ol (HSR-719). From the results, these derivatives were not considered to be adequate for central muscle relaxant. Among the MP derivatives, (4'-chloro-2'-methoxy-3-piperidino) propiophenone HCl (HSR-733) and (4'-ethyl-2-methyl-3-pyrrolidino) propiophenone HCl (HSR-770) strongly inhibited the cooperative movement in the rotating rod method using mice, and it exerted almost the same depressant activity on the cross extensor reflex using alpha-chloralose anesthetized rats. However, the inhibitory effects of HSR-733 on the anemic decerebrate rigidity and the rigidity induced by intracollicular decerebration in rats were weaker than those of HSR-770 and eperisone. In spinal cats, at a low dose (5 mg/kg, i.v.), HSR-733 depressed monosynaptic and dorsal root reflex potentials as compared with polysynaptic reflex potentials, and inhibitory effects of HSR-733 on these three reflex potentials were more potent than those of eperisone and HSR-770. Although HSR-770 acts on the spinal cord and supraspinal level on which eperisone has been reported to act, HSR-733 may mainly act on the spinal cord. These results indicate that the MP derivative with a 2-methyl group may be suitable as a central muscle relaxant. HSR-770, which has equipotent muscle relaxant activity to eperisone, exerted strong inhibitory effects on oxotremorine-induced tremor and weak inhibitory effects on spontaneous motor activity in the

Anthrarobin and its derivatives: evaluation of antibacterial and lipoxygenase inhibition activities

International Nuclear Information System (INIS)

Lateef, M.; Iqbal, S.

2013-01-01

The antibacterial activity of anthrarobin and its synthesized derivatives 1, 10-dihydoxyanthracen-2-0-acetate (1) and anthracen-1, 2-10-tri-O-acetate (2) is determined against two Gram-negative bacteria (Escherichia coli, Pseudomonas aerogenosa) and two Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) along with the lipoxygenase inhibition activity. Gentamycin (0.3 %) was used as standard antibiotic for antibacterial assay. The minimum inhibitory concentration (MIC) was determined by agar well diffusion method. Anthrarobin showed highest antibacterial activity against all the tested bacteria while anthracen-1, 2-10-tri-0-acetate (2) exhibited 97 % activity against Gram-positive bacteria, Staphylococcus aureus, and; 36 % activity against Gram-negative bacteria Escherichia coli. On the other hand, 1, 10-dihydoxyanthracen-2-0-acetate (1) remained non-significant against all the bacteria tested. When anthrarobin and its derivatives were analyzed for lipoxygenase inhibition studies, only anthrarobin showed weak inhibition activity with IC 5 0 value of 65.2 μM. It is concluded that anthrarobin has significant potential for antibacterial activity as compared to its synthesized derivatives. Structure-activity relationship suggests that numbers of hydroxyl group in anthrarobin may be responsible for antimicrobial activity and the activity decreases with the substitution of acyl groups in synthesized derivatives. (author)

Analysis of 3D stacked fully functional CMOS Active Pixel Sensor detectors

International Nuclear Information System (INIS)

Passeri, D; Servoli, L; Meroli, S

2009-01-01

The IC technology trend is to move from 3D flexible configurations (package on package, stacked dies) to real 3D ICs. This is mainly due to i) the increased electrical performances and ii) the cost of 3D integration which may be cheaper than to keep shrinking 2D circuits. Perspective advantages for particle tracking and vertex detectors applications in High Energy Physics can be envisaged: in this work, we will focus on the capabilities of the state-of-the-art vertical scale integration technologies, allowing for the fabrication of very compact, fully functional, multiple layers CMOS Active Pixel Sensor (APS) detectors. The main idea is to exploit the features of the 3D technologies for the fabrication of a ''stack'' of very thin and precisely aligned CMOS APS layers, leading to a single, integrated, multi-layers pixel sensor. The adoption of multiple-layers single detectors can dramatically reduce the mass of conventional, separated detectors (thus reducing multiple scattering issues), at the same time allowing for very precise measurements of particle trajectory and momentum. As a proof of concept, an extensive device and circuit simulation activity has been carried out, aiming at evaluate the suitability of such a kind of CMOS active pixel layers for particle tracking purposes.

Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

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Sara P. Y. Che

2017-11-01

Full Text Available Tissue factor (TF-expressing tumor-derived extracellular vesicles (EVs can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231 and pancreatic (BxPC3 and Capan-1 tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8 in human umbilical vein endothelial cells after exposure to EV and various immunologic and chemical inhibitors of TF, FXa, PAR-1, and PAR-2. After 6 h of exposure to tumor-derived EV (pretreated with factor VIIa and FX in vitro, endothelial cells upregulated E-selectin expression and secreted IL-8. These changes were decreased with an anti-TF antibody, FXa inhibitors (FPRCK and EGRCK, and PAR-1 antagonist (E5555, demonstrating that FXa generated by TF-expressing tumor-derived EV was signaling through endothelial PAR-1. Due to weak constitutive PAR-2 expression, these endothelial responses were not induced by a PAR-2 agonist peptide (SLIGKV and were not inhibited by a PAR-2 antagonist (FSLLRY after exposure to tumor-derived EV. In conclusion, we found that TF-expressing cancer-derived EVs activate quiescent endothelial cells, upregulating E-selectin and inducing IL-8 secretion through generation of FXa and cleavage of PAR-1. Conversion of resting endothelial cells to an activated phenotype by TF-expressing cancer-derived EV could promote cancer metastases.

Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity.

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Taira, Norihisa; Katsuyama, Yushi; Yoshioka, Masato; Muraoka, Osamu; Morikawa, Toshio

2018-04-10

l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C-alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives ( 1 - 28 ) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure-function relationships. Although not the most potent inhibitors, 3- O -(2,3-dihydroxypropyl)-2- O -hexyl-l-ascorbic acid ( 6 , IC 50 = 81.4 µM) and 2- O -(2,3-dihydroxypropyl)-3- O -hexyl-l-ascorbic acid ( 20 , IC 50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3- O -alkyl-derivatives ( 2 - 14 ) exhibit stronger inhibitory activity than the corresponding 2- O -alkyl-derivatives ( 16 - 28 ); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1.

Quality of poultry litter-derived granular activated carbon.

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Qiu, Guannan; Guo, Mingxin

2010-01-01

Utilization of poultry litter as a source material for generating activated carbon is a value-added and environmentally beneficial approach to recycling organic waste. In this study, the overall quality of poultry litter-derived granular activated carbon was systematically evaluated based on its various physical and chemical properties. Granular activated carbon generated from pelletized poultry litter following a typical steam-activation procedure possessed numerous micropores in the matrix. The product exhibited a mean particle diameter of 2.59 mm, an apparent density of 0.45 g cm(-3), a ball-pan hardness of 91.0, an iodine number of 454 mg g(-1), and a BET surface area of 403 m(2) g(-1). It contained high ash, nitrogen, phosphorus contents and the trace elements Cu, Zn, and As. Most of the nutrients and toxic elements were solidified and solution-unextractable. In general, poultry litter-based activated carbon demonstrated overall quality comparable to that of low-grade commercial activated carbon derived from coconut shell and bituminous coal. It is promising to use poultry litter as a feedstock to manufacture activated carbon for wastewater treatment.

Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins

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José Neptuno Rodríguez-López

2013-07-01

Full Text Available Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR, has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

Synthesis and evaluation of antimalarial activity of curcumin derivatives

International Nuclear Information System (INIS)

Gomes, Patricia Ramos; Miguel, Fabio Balbino; Almeida, Mauro Vieira de; Couri, Mara Rubia Costa; Oliveira, Michael Eder de; Ferreira, Vanessa Viana; Guimaraes, Daniel Silqueira Martins; Lima, Aline Brito de; Barbosa, Camila de Souza; Oliveira, Mariana Amorim de; Almeida, Mauro Vieira de; Viana, Gustavo Henrique Ribeiro; Varotti, Fernando de Pilla

2014-01-01

ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC 50 values ranging from 1.7 to 15.2 μg mL -1 ), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

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Mireille Fouillaud

2016-03-01

Full Text Available Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances.

Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities.

Science.gov (United States)

Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

2016-03-25

Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi's productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances.

Design, Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives

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Anwei Ding

2013-08-01

Full Text Available A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole. Compounds M28, M33, and M35 showed higher inhibitory activity against influenza virus H3N2 with their TC50 values being 96.4, 71.0 and 75.4 μM, respectively. Preliminary biological activity evaluation indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through the introduction of halogen into the structure of schizonepetin.

Evaluation of antituberculosis activity and DFT study on dipyrromethane-derived hydrazone derivatives

Science.gov (United States)

Rawat, Poonam; Singh, R. N.; Niranjan, Priydarshni; Ranjan, Alok; Holguín, Norma Rosario Flores

2017-12-01

This paper evaluates the anti-tubercular activity of dipyrromethane-derived hydrazones derivatives (3a-d) against strain of Mycobacterium tuberculosis H37Rv. The newly synthesized compounds have been obtained in good yield based on the condensation of aromatic aldehyde derivatives with pyrrole hydrazone in presence of catalyst and well characterized with spectroscopic methods (1H, 13C NMR, Mass spectrometry) and elemental analysis. The singlet observed in the experimental 1H and 13C NMR spectra in the range of 5.3-5.7 ppm and 30-33.86 ppm, respectively, indicating that two pyrrole units are joined at meso position. The electronic transitions observed in the experimental spectra are n→π* and π →π* in nature. Experimental and theoretical findings corroborate well with each other. The substitution of acceptor group (-NO2) at ortho- and meta-positions of benzene ring, present at meso-position of dipyrromethane is responsible for variation in β0 values. The calculated NLO of (3a-d) are much greater than those of p-nitroaniline (PNA). The solvent induced effects on the non-linear optical properties were studied and found to enhance NLO properties of the molecules as dielectric constants of the solvents increases. On the basis of results it is anticipated that these dipyrromethanes will be useful for both antimicrobial and non-linear optical (NLO) applications. With the help of Microplate Alamar Blue assay (MABA) method all (3a-d) compounds were screened for their anti-tubercular activity and found that 3b and 3d have higher inhibitory activity against strain of M. tuberculosis H37Rv.

Temporally coordinated spiking activity of human induced pluripotent stem cell-derived neurons co-cultured with astrocytes.

Science.gov (United States)

Kayama, Tasuku; Suzuki, Ikuro; Odawara, Aoi; Sasaki, Takuya; Ikegaya, Yuji

2018-01-01

In culture conditions, human induced-pluripotent stem cells (hiPSC)-derived neurons form synaptic connections with other cells and establish neuronal networks, which are expected to be an in vitro model system for drug discovery screening and toxicity testing. While early studies demonstrated effects of co-culture of hiPSC-derived neurons with astroglial cells on survival and maturation of hiPSC-derived neurons, the population spiking patterns of such hiPSC-derived neurons have not been fully characterized. In this study, we analyzed temporal spiking patterns of hiPSC-derived neurons recorded by a multi-electrode array system. We discovered that specific sets of hiPSC-derived neurons co-cultured with astrocytes showed more frequent and highly coherent non-random synchronized spike trains and more dynamic changes in overall spike patterns over time. These temporally coordinated spiking patterns are physiological signs of organized circuits of hiPSC-derived neurons and suggest benefits of co-culture of hiPSC-derived neurons with astrocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis, Characterization and Antimicrobial Activity of New Thiadiazole Derivatives

Energy Technology Data Exchange (ETDEWEB)

Mullick, Pooja; Khan, Suroor A.; Verma, Surajpal; Alam, Ozair [Hamdard University, New Delhi (India)

2010-08-15

A series of thiadiazole derivatives were synthesized with differently substituted benzoic acids which were cyclized to give differently substituted thiazolidin-4-one. Elemental analysis, IR, {sup 1}H NMR, {sup 13}C NMR and mass spectral data confirmed the structure of the newly synthesized compounds. The derivatives of these moieties were evaluated for antimicrobial activity. Most of the synthesized compounds showed good antimicrobial activity at 200 and 100 μg/mL. Compounds showed most significant antibacterial activity against gram negative test organism Escherichia coli and most significant antifungal activity against test organisms Aspergillus niger and Candida albicans. It was observed that compounds with OCH{sub 3} at 3, 4 position of phenyl ring [5(a-l)] were more potent against microbes as compared to compounds having unsubstituted phenyl ring [4(a-l)].

Antioxidant Activity of Novel Fused Heterocyclic Compounds Derived from Tetrahydropyrimidine Derivative.

Science.gov (United States)

Salem, Marwa Sayed; Farhat, Mahmoud; Errayes, Asma Omar; Madkour, Hassan Mohamed Fawzy

2015-01-01

6-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile has been utilized for synthesis of the fused heterocyclic compounds namely thiazolopyrimidines, tetrazolopyrimidine, pyrimidoquinazoline, pyrimidothiazolopyrimidine, pyrimidothiazolotriazine and pyrrolothiazolopyrimidine derivatives. The newly synthesized compounds were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. Antioxidant activities of all synthesized compounds were investigated.

Biochemical activity of fullerenes and related derivatives

International Nuclear Information System (INIS)

Huczko, A.; Lange, H.; Calko, E.

1999-01-01

An astonishing scientific interest, embodied in over 15000 research articles so far, has been encountered since 1985 when fullerenes were discovered. From new superconductors to a rich electrochemistry and reaction chemistry, fullerene nanostructures continue to excite the scientific world, and new findings continue at record pace. This review presents many examples of the biochemical activities of fullerenes and derivatives, e. g. cytotoxic activity, selective DNA cleavage and antiviral activity against HIV. We also present some results of our testing which show that, despite its chemical and biochemical activity, fullerene matter does not present any health hazard directly related to skin irritation and allergic risks. (author)

Renormalization-group improved fully differential cross sections for top pair production

International Nuclear Information System (INIS)

Broggio, A.; Papanastasiou, A.S.; Signer, A.; Zuerich Univ.

2014-07-01

We extend approximate next-to-next-to-leading order results for top-pair production to include the semi-leptonic decays of top quarks in the narrow-width approximation. The new hard-scattering kernels are implemented in a fully differential parton-level Monte Carlo that allows for the study of any IR-safe observable constructed from the momenta of the decay products of the top. Our best predictions are given by approximate NNLO corrections in the production matched to a fixed order calculation with NLO corrections in both the production and decay subprocesses. Being fully differential enables us to make comparisons between approximate results derived via different (PIM and 1PI) kinematics for arbitrary distributions. These comparisons reveal that the renormalization-group framework, from which the approximate results are derived, is rather robust in the sense that applying a realistic error estimate allows us to obtain a reliable prediction with a reduced theoretical error for generic observables and analysis cuts.

Behaviour of Viscoelastic - Viscoplastic Spheres and Cylinders - Fully Plastic Vessel Walls

DEFF Research Database (Denmark)

Ottosen, N. Saabye

1985-01-01

The material model consists of a viscoelastic Burgers element and an additional viscoplastic Bingham element when the effective stress exceeds the yield stress. For fully plastic vessel walls, exact closed-form expressions arc derived for the stress and strain state in pressurised or relaxation...... loaded thick-walled cylinders in plane strain and spheres. For the spherical problem, the material compressibility is accounted for. The influence of the different material parameters on the behaviour of the vessels is evaluated. It is shown that the magnitude of the Maxwell viscosity is of major...... importance for the long-term behaviour of thick-walled fully plastic vessels....

Detection of Transketolase in Bone Marrow—Derived Insulin-Producing Cells: Benfotiamine Enhances Insulin Synthesis and Glucose Metabolism

OpenAIRE

Oh, Seh-Hoon; Witek, Rafal P.; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E.

2009-01-01

Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the prolife...

Allobetulin and Its Derivatives: Synthesis and Biological Activity

Directory of Open Access Journals (Sweden)

Talgat S. Seitembetov

2011-03-01

Full Text Available This review covers the chemistry of allobetulin analogs, including their formation by rearrangement from betulin derivatives, their further derivatisation, their fusion with heterocyclic rings, and any further rearrangements of allobetulin compounds including ring opening, ring contraction and ring expansion reactions. In the last part, the most important biological activities of allobetulin derivatives are listed. One hundred and fifteen references are cited and the relevant literature is covered, starting in 1922 up to the end of 2010.

Synthesis and Antimicrobial Activities of Some Novel Quinoxalinone Derivatives

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Y. A. Ammar

2000-06-01

Full Text Available Condensation of 4-benzoyl-1,2-phenylenediamine with sodium pyruvate in acetic acid furnished two products which were identified as 6-benzoyl and 7-benzoyl-3-methyl-2(1Hquinoxalinones (1a,b. Fusion of 1a with aromatic aldehydes furnished the styryl derivatives 2a-c. Alkylation of 1a,b with dimethyl sulphate or ethyl chloroacetate produced the N-alkyl derivatives 3a,b and 4a,b. Hydrazinolysis of the ester derivative 4a with hydrazine hydrate afforded the hydrazide derivative 5 which underwent condensation with aldehydes to give the corresponding hydrazone derivatives 6a,b. In addition, chlorination of 1a with thionyl chloride afforded the 2-chloro derivative 7 which was subjected to reaction with sodium azide and n-butylamine to yield the corresponding tetrazolo (8 and n-butylamino (9 derivatives, respectively. The structures of the compounds prepared were confirmed by analytical and spectral data. Also, some of the synthesized compounds were screened for antimicrobial activity.

Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks

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Heikki Kiiski

2013-05-01

The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC-derived neural cells could be cultured in human cerebrospinal fluid (CSF in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

Facile Chemical Access to Biologically Active Norcantharidin Derivatives from Biomass

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Konstantin I. Galkin

2017-12-01

Full Text Available Reductive amination of 2,5-diformylfuran (DFF was used to implement the transition from bio-derived 5-hydroxymethylfurfural (HMF to pharmaceuticals. The synthesized bis(aminomethylfurans were utilized as building blocks for the construction of new derivatives with structural cores of naturally occurring biologically active compounds. Using the one-pot procedure, which included the Diels–Alder reaction followed by hydrogenation of the double bond, bio-derived analogues of the anticancer drug norcantharidin were obtained. The cyclization process was diastereoselective, and resulted in the formation of tricyclic products with the endo configuration. Analysis of cytotoxycity for the resulting tricyclic amine-containing compounds showed an increase of anticancer activity as compared with the unsubstituted norcantharimide.

Determination of phosphorus using derivative neutron activation

International Nuclear Information System (INIS)

Scindia, Y.M.; Nair, A.G.C.; Reddy, A.V.R.; Manohar, S.B.

2002-01-01

For the determination of phosphorus in different matrices, the derivative neutron activation analysis is especially applicable to aqueous samples, since the conventional neutron activation analysis is not useful for the determination of phosphorus. Phosphorus when reacted with ammonium molybdate 4 hydrate and ammonium metavanadate forms molybdo vanado phosphoric acid. This complex is preconcentrated by extracting into methyl isobutyl ketone. The organic phase containing the molybdo vanado phosphoric acid is neutron activated and the phosphorus is determined through the activation product of 52 V. Preparation of this complex, its stoichiometry, application to trace level determination of phosphorus and improved detection limit are discussed. This method was applied for the analysis of industrial effluent samples. (author)

EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

Science.gov (United States)

Iacob, Andreea-Teodora; Drăgan, Maria; Constantin, Sandra; Lupaşcu, Florentina; Confederat, Luminiţa; Buron, F; Routier, S; Profire, Lenuţa

2016-01-01

L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

Studies on Synthesis of Some Novel Heterocyclic Azlactone Derivatives and Imidazolinone Derivatives and their Antimicrobial Activity

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Rakesh N. Mistry

2005-01-01

Full Text Available p - Methyl benzoic acid on reaction with phosphorus pentachloride gives p - methyl benzoyl chloride derivative which on condensation with glycine gives p - methyl benzoyl glycine derivative. Now, this p - methyl benzoyl glycine derivative on condensation with various substituted aldehydes gives corresponding substituted 4 - [aryl methylidine] - 2 - [p - methyl phenyl] - oxazole - 5 - one derivatives [1(a-j]. Further, these derivatives [1(a-j] on condensation with 4 , 4’ - diamino diphenyl sulphone gives corresponding substituted imidazolinone - dibenzsulphone derivatives [2(a-j], on condensation with 4 , 4’ - diamino diphenyl methane gives corresponding substituted imidazolinone - dibenzmethane derivatives [3(a-j], on condensation with 4,4’- diamino benzanilide gives corresponding substituted imidazolinone - benzanilide derivatives [4(a-j] and on condensation with 2 - amino pyridine gives corresponding substituted imidazolinone - pyridine derivatives [5(a-j] respectively. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene-2-propylpentane hydrazide-hydrazones Derivatives

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Ayman El-Faham

2015-08-01

Full Text Available Eight novel N′-(2-oxoindolin-3-ylidene-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR (1H-NMR and 13C-NMR, elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2 and leukaemia (Jurkat, as well as in normal cell lines derived from human embryonic kidney (HEK293 using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32–50 μM. Among the tested compounds, 4a showed specificity against leukaemia (Jurkat cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells.

Science.gov (United States)

Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Takikawa, Tetsuya; Nabeshima, Tatsuhide; Shimosegawa, Tooru

2018-01-01

Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential Biosignificant Interest and Surface Activity of Efficient Heterocyclic Derivatives.

Science.gov (United States)

El-Sayed, Refat; Althagafi, Ismail

2016-01-01

Some functionalized pyridine and fused system derivatives were synthesized using enaminonitrile derivative 5 as a starting material for the reaction, with various reagents under different conditions. Propoxylation of these compounds using different moles of propylene oxide (3, 5 and 7 moles) leads to a novel group of surface active agents. The antimicrobial and surface activities of the synthesized compounds were investigated. Most of the evaluated compounds proved to be active as antibacterial and antifungal agents and showed good surface activity, which makes them suitable for diverse applications such as the manufacturing of emulsifiers, cosmetics, drugs, pesticides, etc. Additionally, biodegradation testing exhibits significant breakdown within six to seven days, and hence, lowers the toxicity to human beings and becomes environmentally friendly.

Calculation of Quantitative Structure-Activity Relationship Descriptors of Artemisinin Derivatives

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Jambalsuren Bayarmaa

2008-06-01

Full Text Available Quantitative structure-activity relationships are based on the construction of predictive models using a set of known molecules and associated activity value. This accurate methodology, developed with adequate mathematical and computational tools, leads to a faster, cheaper and more comprehensive design of new products, reducing the experimental synthesis and testing on animals. Preparation of the QSAR models of artemisinin derivatives was carried out by the genetic function algorithm (GFA method for 91 molecules. The results show some relationships to the observed antimalarial activities of the artemisinin derivatives. The most statistically signi fi cant regression equation obtained from the fi nal GFA relates to two molecular descriptors.

Human induced pluripotent stem cell (hiPSC)-derived neurons respond to convulsant drugs when co-cultured with hiPSC-derived astrocytes.

Science.gov (United States)

Ishii, Misawa Niki; Yamamoto, Koji; Shoji, Masanobu; Asami, Asano; Kawamata, Yuji

2017-08-15

Accurate risk assessment for drug-induced seizure is expected to be performed before entering clinical studies because of its severity and fatal damage to drug development. Induced pluripotent stem cell (iPSC) technology has allowed the use of human neurons and glial cells in toxicology studies. Recently, several studies showed the advantage of co-culture system of human iPSC (hiPSC)-derived neurons with rodent/human primary astrocytes regarding neuronal functions. However, the application of hiPSC-derived neurons for seizure risk assessment has not yet been fully addressed, and not at all when co-cultured with hiPSC-derived astrocytes. Here, we characterized hiPSC-derived neurons co-cultured with hiPSC-derived astrocytes to discuss how hiPSC-derived neurons are useful to assess seizure risk of drugs. First, we detected the frequency of spikes and synchronized bursts hiPSC-derived neurons when co-cultured with hiPSC-derived astrocytes for 8 weeks. This synchronized burst was suppressed by the treatment with 6-cyano-7-nitroquinoxaline-2,3-dione, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, and D-(-)-2-amino-5-phosphonopentanoic acid, an N-Methyl-d-aspartate (NMDA) receptor antagonist. These data suggested that co-cultured hiPSC-derived neurons formed synaptic connections mediated by AMPA and NMDA receptors. We also demonstrated that co-cultured hiPSC-derived neurons showed epileptiform activity upon treatment with gabazine or kaliotoxin. Finally, we performed single-cell transcriptome analysis in hiPSC-derived neurons and found that hiPSC-derived astrocytes activated the pathways involved in the activities of AMPA and NMDA receptor functions, neuronal polarity, and axon guidance in hiPSC-derived neurons. These data suggested that hiPSC-derived astrocytes promoted the development of action potential, synaptic functions, and neuronal networks in hiPSC-derived neurons, and then these functional alterations result in the epileptiform

Exact stationary state for an asymmetric exclusion process with fully parallel dynamics

NARCIS (Netherlands)

Gier, J.C.|info:eu-repo/dai/nl/170218430; Nienhuis, B.

The exact stationary state of an asymmetric exclusion process with fully parallel dynamics is obtained using the matrix product ansatz. We give a simple derivation for the deterministic case by a physical interpretation of the dimension of the matrices. We prove the stationarity via a cancellation

A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity.

Science.gov (United States)

Sadashiva, Maralinganadoddi P; Gowda, Raghavendra; Wu, Xianzhu; Inamdar, Gajanan S; Kuzu, Omer F; Rangappa, Kanchugarakoppal S; Robertson, Gavin P; Gowda, D Channe

2015-08-01

Malaria caused by the Plasmodium parasites continues to be an enormous global health problem owing to wide spread drug resistance of parasites to many of the available antimalarial drugs. Therefore, development of new classes of antimalarial agents is essential to effectively treat malaria. In this study, the efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic acid, and their synthetic derivatives was assessed for antimalarial activity. Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N-benzyl derivatives showed excellent activity against P. falciparum parasites with IC50 values of 0.36 to 2.6 µM. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100 µM) to mammalian cells; thus, this compound can be an important antimalarial drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50 value of ~82 µM. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of ~8.2 to ~13.3 µM. These results suggest that a detailed understanding of the structure-activity relationship of abietane diterpenoids might provide strategies to exploit this class of compounds for malaria treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

Energy Technology Data Exchange (ETDEWEB)

Liu, X.-F. [Huazhong Univ. of Science and Technology, Dept. of Chemistry, Wuhan (China); Hubei Univ., Ministry of Education Key Lab. for the Synthesis and Application of Organic Functional Molecules, Wuhan (China); Guan, W.-C. [Huazhong Univ. of Science and Technology, Dept. of Chemistry, Wuhan (China)], E-mail: wcguan04@yahoo.com.cn; Ke, W.-S. [Hubei Univ., College of Life Science, Wuhan (China)

2007-03-15

A C{sub 60}-based ebselen derivative 4 was synthesized through the cycloaddition of C{sub 60} with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C{sub 60}). Its structure was characterized by {sup 1}H NMR, {sup 13}C NMR, IR, UV, and FAB-MS. To verify that the C{sub 60}-based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C{sub 60} derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C{sub 60}-based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 {mu}mol/L), the results showed that the antioxidative and protective potencies of the C{sub 60}-based ebselen derivative 4 (MTT (OD) 0.340 {+-} 0.035, LDH release (UL{sup -1}) 4.80 {+-} 0.16) against H{sub 2}O{sub 2}-mediated neuronal injury have an advantage over those of C{sub 60} derivative 5 (MTT (OD) 0.297 {+-} 0.036, LDH release (UL{sup -1}) 5.37 {+-} 0.31) and ebselen derivative 6 (MTT (OD) 0.267 {+-} 0.027, LDH release (UL{sup -1}) 5.85 {+-} 0.26). Correspondingly, the GPX activity of 4 (1.62 U/{mu}mol) was higher than that of 5 (0.77 U/{mu}mol) and 6 (1.24 U/{mu}mol). These findings demonstrate that the incorporation of two components with similar biological activity (C{sub 60} component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C{sub 60}-based compound. (author)

Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives

International Nuclear Information System (INIS)

Liu, X.-F.; Guan, W.-C.; Ke, W.-S.

2007-01-01

A C 60 -based ebselen derivative 4 was synthesized through the cycloaddition of C 60 with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C 60 ). Its structure was characterized by 1 H NMR, 13 C NMR, IR, UV, and FAB-MS. To verify that the C 60 -based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C 60 derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C 60 -based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 μmol/L), the results showed that the antioxidative and protective potencies of the C 60 -based ebselen derivative 4 (MTT (OD) 0.340 ± 0.035, LDH release (UL -1 ) 4.80 ± 0.16) against H 2 O 2 -mediated neuronal injury have an advantage over those of C 60 derivative 5 (MTT (OD) 0.297 ± 0.036, LDH release (UL -1 ) 5.37 ± 0.31) and ebselen derivative 6 (MTT (OD) 0.267 ± 0.027, LDH release (UL -1 ) 5.85 ± 0.26). Correspondingly, the GPX activity of 4 (1.62 U/μmol) was higher than that of 5 (0.77 U/μmol) and 6 (1.24 U/μmol). These findings demonstrate that the incorporation of two components with similar biological activity (C 60 component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C 60 -based compound. (author)

Chitosan derivatives with antimicrobial, antitumour and antioxidant activities--a review.

Science.gov (United States)

Jarmila, Vinsová; Vavríková, Eva

2011-01-01

Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film that protects cells against nutrient transport through the microbial cell membrane. Low molecular weight chitosan derivatives are water soluble and can better incorporate the active molecule into the cell. Gram-negative bacteria, often represented by Escherichia coli, have an anionic bacterial surface on which cationic chitosan derivatives interact electrostatically. Thus, many chitosan conjugates have cationic components such as ammonium, pyridinium or piperazinium substituents introduced into their molecules to increase their positive charge. Gram-positive bacteria like Staphylococcus aureus are inhibited by the binding of lower molecular weight chitosan derivatives to DNA or RNA. Chitosan nanoparticles exhibit an increase in loading capacity and efficacy. Antitumour active compounds such as doxorubicin, paclitaxel, docetaxel and norcantharidin are used as drug carriers. It is evident that chitosan, with its low molecular weight, is a useful carrier for molecular drugs requiring targeted delivery. The antioxidant scavenging activity of chitosan has been established by the strong hydrogen-donating ability of chitosan. The low molecular weight and greater degree of quarternization have a positive influence on the antioxidant activity

Design, Synthesis, and Insecticidal Activity of Some Novel Diacylhydrazine and Acylhydrazone Derivatives

Directory of Open Access Journals (Sweden)

Jialong Sun

2015-03-01

Full Text Available In this study a series of diacylhydrazine and acylhydrazone derivatives were designed and synthesized according to the method of active group combination and the principles of aromatic group bioisosterism. The structures of the novel derivatives were determined on the basis on 1H-NMR, IR and ESI-MS spectral data. All of the compounds were evaluated for their in vivo insecticidal activity against the third instar larvae of Spodoptera exigua Hiibner, Helicoverpa armigera Hubner, Plutella xyllostella Linnaeus and Pieris rapae Linne, respectively, at a concentration of 10 mg/L. The results showed that all of the derivatives displayed high insecticidal activity. Most of the compounds presented higher insecticidal activity against S. exigua than the reference compounds tebufenozide, metaflumizone and tolfenpyrad, and approximately identical insecticidal activity against H. armigera, P. xyllostella and P. rapae as the references metaflumizone and tolfenpyrad.

Plant derived substances with anti-cancer activity: from folklore to practice

Directory of Open Access Journals (Sweden)

Marcelo eFridlender

2015-10-01

Full Text Available Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.

Isocorydine Derivatives and Their Anticancer Activities

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Mei Zhong

2014-08-01

Full Text Available In order to improve the anticancer activity of isocorydine (ICD, ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8 and 6a,7-dihydrogen-isocorydione (10 could inhibit the growth of human lung (A549, gastric (SGC7901 and liver (HepG2 cancer cell lines in vitro. Isocorydione (2 could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11, a pro-drug of 8-amino-isocorydine (8, which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.

An overview on benzylisoquinoline derivatives with dopaminergic and serotonergic activities.

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Cabedo, N; Berenguer, I; Figadère, B; Cortes, D

2009-01-01

Dopamine and serotonin are important neurotransmitters in the mammalian central nervous system (CNS) involved in numerous physiological and behavioural disorders such as schizophrenia, major depression, anxiety, Parkinson's and Huntington's diseases, and attention deficit hyperactivity disorder. Several natural and synthetic benzylisoquinoline derivatives have displayed affinity for dopamine and serotonin receptors in nanomolar or micromolar ranges. This review covers the last three decades of dopaminergic and serotonergic activities, and especially focuses on structure-activity relationships of natural and synthetic benzylisoquinoline derivatives. We have included aporphines, 1-benzyltetrahydroisoquinolines, bis-benzylisoquinolines, protoberberines, cularines and other structural analogues. Further molecular modelling calculations have been considered as important tools to not only obtain structural information of both neurotransmitter receptors, but to also identify their pharmacophore features. The development of selective potential ligands like benzylisoquinoline derivatives may help in the therapy of diseases related to CNS dysfunction.

Microwave Assisted Synthesis of Some New Heterocyclic Spiro-Derivatives with Potential Antimicrobial and Antioxidant Activity

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Mohamed Mohamed Youssef

2010-12-01

Full Text Available Homophthalic anhydride reacts with different aromatic amines to produce N-substituted homophthalimides. Bromination of the latter produces 4,4-dibromo-homophthalimide derivatives that can be used as precursors for spiro-derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiro-isoquinoline derivatives. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro-derivatives. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, 1H-NMR and 13C-NMR. The newly synthesized compounds were tested for their antimicrobial and antioxidant activities, showing weak or no antimicrobial activity. On the other hand select compounds showed promising antioxidant activities.

Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

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Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

2013-07-01

A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chitosan derivatives targeting lipid bilayers: Synthesis, biological activity and interaction with model membranes.

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Martins, Danubia Batista; Nasário, Fábio Domingues; Silva-Gonçalves, Laiz Costa; de Oliveira Tiera, Vera Aparecida; Arcisio-Miranda, Manoel; Tiera, Marcio José; Dos Santos Cabrera, Marcia Perez

2018-02-01

The antimicrobial activity of chitosan and derivatives to human and plant pathogens represents a high-valued prospective market. Presently, two low molecular weight derivatives, endowed with hydrophobic and cationic character at different ratios were synthesized and characterized. They exhibit antimicrobial activity and increased performance in relation to the intermediate and starting compounds. However, just the derivative with higher cationic character showed cytotoxicity towards human cervical carcinoma cells. Considering cell membranes as targets, the mode of action was investigated through the interaction with model lipid vesicles mimicking bacterial, tumoral and erythrocyte membranes. Intense lytic activity and binding are demonstrated for both derivatives in anionic bilayers. The less charged compound exhibits slightly improved selectivity towards bacterial model membranes, suggesting that balancing its hydrophobic/hydrophilic character may improve efficiency. Observing the aggregation of vesicles, we hypothesize that the "charge cluster mechanism", ascribed to some antimicrobial peptides, could be applied to these chitosan derivatives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fully-developed heat transfer in annuli with viscous dissipation

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Coelho, P.M. [Universidade do Porto, Porto (Portugal). Centro de Estudos de Fenomenos de Transporte, DEMEGI, Faculdade de Engenharia; Pinho, F.T. [Universidade do Porto, Porto (Portugal). Centro de Estudos de Fenomenos de Transporte, Faculdade de Engenharia

2006-09-15

For Newtonian concentric annular flows analytical solutions are obtained under imposed asymmetric constant wall heat fluxes as well as under imposed asymmetric constant wall temperatures, taking into account viscous dissipation and for fluid dynamic and thermally fully-developed conditions. Results for the special case of the heat flux ratio for identical wall temperatures and the critical Brinkman numbers marking changes of sign in wall heat fluxes are also derived. Equations are presented for the Nusselt numbers at the inner and outer walls, bulk temperature and normalised temperature distribution as a function of all relevant non-dimensional numbers. Given the complexity of the derived equations, simpler exact expressions are presented for the Nusselt numbers for ease of use, with their coefficients given in tables as a function of the radius ratio. (author)

Preparation and physiological activities of carboxymethylated derivative purified from corn bran

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Zhu, Linghui; Fang, Miaoli; Ma, Jianjun; Mo, Qing

2017-06-01

Two water-soluble polysaccharides extracted from corn bran were chemically modified to obtain their carboxymethylated derivatives (C-CBP1, C-CBP2). Theresults of degree of substitution and FT-IR analysis showed the carboxymethylation of polysaccharides were successful. The average molecular weight (Mw) of C-CBP1 and C-CBP2 were 368 and 263kDa, respectively. The degree of substitution (DS) of C-CBP1 and C-CBP2 were determined to be 0.44 and 0.46. The results showed that derivatives were effective in antioxidant and bile acidbinding activityin a dose dependent way. And C-CBP2 had the higher activity for hydroxyl radical, superoxide anion scavenging activities and bile acid capacity, as lower molecular weight plays a critical role in antioxidant activities and bile acid capacity. The results suggest that the carboxymethylated derivatives are potential natural antioxidant and blood fat reduce agent that can be used as drugs or functional food ingredients.

Antimicrobial and immunomodulatory activities of PR-39 derived peptides.

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Edwin J A Veldhuizen

Full Text Available The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics.

Antimicrobial and Immunomodulatory Activities of PR-39 Derived Peptides

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Veldhuizen, Edwin J. A.; Schneider, Viktoria A. F.; Agustiandari, Herfita; van Dijk, Albert; Tjeerdsma-van Bokhoven, Johanna L. M.; Bikker, Floris J.; Haagsman, Henk P.

2014-01-01

The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics. PMID:24755622

Antibacterial Characteristics and Activity of Water-Soluble Chitosan Derivatives Prepared by the Maillard Reaction

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Ying-Chien Chung

2011-10-01

Full Text Available The antibacterial activity of water-soluble chitosan derivatives prepared by Maillard reactions against Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Escherichia coli, Shigella dysenteriae, and Salmonella typhimurium was examined. Relatively high antibacterial activity against various microorganisms was noted for the chitosan-glucosamine derivative as compared to the acid-soluble chitosan. In addition, it was found that the susceptibility of the test organisms to the water-soluble chitosan derivative was higher in deionized water than in saline solution. Metal ions were also found to reduce the antibacterial activity of the water-soluble chitosan derivative on S. aureus. The marked increase in glucose level, protein content and lactate dehydrogenase (LDH activity was observed in the cell supernatant of S. aureus exposed to the water-soluble chitosan derivative in deionized water. The results suggest that the water-soluble chitosan produced by Maillard reaction may be a promising commercial substitute for acid-soluble chitosan.

Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

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Oee-Sook Park

2009-11-01

Full Text Available The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

synthesis and characterization of some poly functionalized heterocyclic derivatives of expected biological activity

International Nuclear Information System (INIS)

El-sayed, M.S.

2001-01-01

The present work was aimed and designed to fulfil The following objectives : 1- Continuation of the effort done by our research group in the field of chemistry of pyridinethione derivatives and their biological activities. 2- Synthesis of several new heterocyclic derivatives containing N and/or S using the laboratory available reagents. 3- Establishment of the structures of the newly synthesized heterocyclic compounds by the data of IR, 1 H-NMR, mass spectra in addition to the elemental analysis. 4- Synthesis of some of these heterocyclic derivatives via alternative routs and this used as a tool to confirm the structures of the newly synthesized heterocyclic derivatives. 5- study of the most probable mechanisms leading to the formation of the new heterocyclic derivatives. 6- The antimicrobial activity of some of the newly synthesized heterocyclic derivatives was tested against several types of organisms

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.

Synthesis and Antimicrobial Activity of Some New Formazan Derivatives

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S. I. Marjadi

2009-01-01

Full Text Available A series of new substituted formazan derivatives has been synthesized from corresponding aryl diazonium chloride and Schiff base in pyridine. The synthesized compounds were identified by spectral studies and screened for their antimicrobial activities.

Synthesis and anticonvulsant activity of some 2-pyrazolines derived from chalcones

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Nagihan Beyhan

2017-05-01

All compounds were tested for their anticonvulsant activity using pentylenetetrazole induced seizure (PTZ and maximal electroshock seizure (MES tests in mice at a dose level of 50 mg/kg. Among the 2-pyrazoline-1-carbothioamide derivatives, 5-(2,6-dichlorophenyl-3-(thiophen-2-yl-4,5-dihydro-1H-pyrazole-1-carbothioamide (2e reduced grade-5 seizure activity and also increased survival rate in PTZ test. In MES test, 5-(4-methoxyphenyl-3-[4-(methylsulphonylphenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide(2g has not only decreased seizure severity, but also increased survival rate. Among the 2-pyrazoline-1-carboxamide derivatives, 3-(5-bromothiophen-2-yl-N-(4-chlorophenyl-5-(2,6-dichlorophenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (3d having 5-bromothiophen and 2,6-dichlorophenyl moieties and N-(4-chlorophenyl-5-(2,6-dichlorophenyl-3-(5-chlorothiophen-2-yl-4,5-dihydro-1H-pyrazole-1-carboxamide (3e having 5-chlorothiophen and 2,6-dichlorophenyl moieties showed remarkable activities in PTZ test. Among all tested derivatives, compound 3d was found to be the most active one and reduced grade-5 seizure severity and also increased survival rate.

A new learning algorithm for a fully connected neuro-fuzzy inference system.

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Chen, C L Philip; Wang, Jing; Wang, Chi-Hsu; Chen, Long

2014-10-01

A traditional neuro-fuzzy system is transformed into an equivalent fully connected three layer neural network (NN), namely, the fully connected neuro-fuzzy inference systems (F-CONFIS). The F-CONFIS differs from traditional NNs by its dependent and repeated weights between input and hidden layers and can be considered as the variation of a kind of multilayer NN. Therefore, an efficient learning algorithm for the F-CONFIS to cope these repeated weights is derived. Furthermore, a dynamic learning rate is proposed for neuro-fuzzy systems via F-CONFIS where both premise (hidden) and consequent portions are considered. Several simulation results indicate that the proposed approach achieves much better accuracy and fast convergence.

Synthesis and antibacterial activity of novel enolphosphate derivatives.

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Grison, Claude; Barthes, Nicolas; Finance, Chantal; Duval, Raphael E

2010-10-01

A new class of enolphosphates derivatives, the 1-alkenyldiphosphates, was designed and a rapid and efficient synthesis for these compounds was developed. These new molecules showed interesting in vitro antibacterial activities (MIC) against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative pathogens including Pseudomonas aeruginosa and Escherichia coli. 2010 Elsevier Inc. All rights reserved.

Synthesis and antimicrobial activities of novel 1,4-benzothiazine derivatives

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Vijay V. Dabholkar

2016-09-01

Full Text Available A series of 2H,4H-2-[3,5-dimethyl-4-(substituted phenyl azo pyrazol-1-yl] carbonyl methyl-3-oxo-1,4-benzothiazine derivatives have been synthesized by the reaction of 2H,4H-2-hydrazino carbonyl methyl-3-oxo-1,4-benzothiazine with acetyl acetone derivatives using ultrasound in lesser time with higher yields. All the synthesized compounds were investigated for their antibacterial activities. The result indicated that the compounds show convincing activities against Gram-positive bacteria (Bacillus subtilis and Streptococcus lactis when compared with standard drug (ampicillin trihydrate. These compounds were also synthesized by conventional method and their structures have been elucidated on the basis of spectral analyses and chemical reactions.

Derivation of criteria for primary circuit activity in an HTGR

International Nuclear Information System (INIS)

Su, S.D.; Barsell, A.W.

1980-11-01

This paper derives specific criteria for the circulating and plateout activity in the primary circuit for a 2170-MW(t) high temperature gas-cooled reactor-gas turbine (HTGR-GT) plant. Results show that for a design basis, (1) the circulating activity should be limited to 14,000 Ci Kr-88 (a principal nuclide) to meet both offsite dose and containment access constraint during normal operation and depressurization accidents, and (2) the plateout inventories for those important nuclides affecting shutdown maintenance should not exceed 10,000 Ci Ag-110m, 45,000 Ci Cs-134 and 130,000 Ci Cs-137. This paper presents bases and methodology for deriving such criteria and compares them with light water reactors. 5 tables

Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives

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Yang Li

2016-02-01

Full Text Available A total of forty novel glycyrrhetinic acid (GA derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231 in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 µM for MCF-7 and MDA-MB-231, respectively and merits further exploration as a new anticancer agent.

Thrombin-specific inactivation of endothelial cell derived plasminogen activator

International Nuclear Information System (INIS)

Highsmith, R.F.; Gallaher, M.J.

1986-01-01

Although thrombin (T) has diverse functions in the overall hemostatic mechanism, relatively little is known about its direct effect on components of the fibrinolytic enzyme system. The authors have investigated the interaction of T with plasminogen activators (PA) derived from bovine aortic endothelial cells (EC) in culture (2-5th passage, preconfluent monolayers). Varying concentrations of purified bovine or human thrombin were added to EC-conditioned media (CM). CM + T mixtures were assayed at various times for PA activity using purified plasminogen and a sensitive 125 I-fibrinogenolytic or caseinolytic assay. T (5 nM), but not plasmin or trypsin at equivalent concentrations, resulted in a time-dependent inhibition of the PA activity in CM. T had no effect on the PA activity of urokinase, streptokinase or preformed plasmin. The ability of T to inactivate the EC-derived PA was abolished by prior treatment of T with active site-directed reagents. SDS-PAGE and zymography with copolymerized fibrinogen and plasminogen revealed further specificity in that only one of the multiple-molecular weight forms of PA present in EC-CM was inactivated by T. The authors conclude that in a highly specific fashion, T inactivates the predominant PA present in EC-CM by limited proteolysis. Thus, another potentially important function of T is suggested which may have particular significance in the temporal regulation of coagulation and fibrinolysis at the blood-endothelium interface

Adsorption Properties of Lignin-derived Activated Carbon Fibers (LACF)

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Contescu, Cristian I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gallego, Nidia C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thibaud-Erkey, Catherine [United Technologies Research Center (UTRC), East Hartford, CT (United States); Karra, Reddy [United Technologies Research Center (UTRC), East Hartford, CT (United States)

2016-04-01

The object of this CRADA project between Oak Ridge National Laboratory (ORNL) and United Technologies Research Center (UTRC) is the characterization of lignin-derived activated carbon fibers (LACF) and determination of their adsorption properties for volatile organic compounds (VOC). Carbon fibers from lignin raw materials were manufactured at Oak Ridge National Laboratory (ORNL) using the technology previously developed at ORNL. These fibers were physically activated at ORNL using various activation conditions, and their surface area and pore-size distribution were characterized by gas adsorption. Based on these properties, ORNL did down-select five differently activated LACF materials that were delivered to UTRC for measurement of VOC adsorption properties. UTRC used standard techniques based on breakthrough curves to measure and determine the adsorption properties of indoor air pollutants (IAP) - namely formaldehyde and carbon dioxide - and to verify the extent of saturated fiber regenerability by thermal treatments. The results are summarized as follows: (1) ORNL demonstrated that physical activation of lignin-derived carbon fibers can be tailored to obtain LACF with surface areas and pore size distributions matching the properties of activated carbon fibers obtained from more expensive, fossil-fuel precursors; (2) UTRC investigated the LACF potential for use in air cleaning applications currently pursued by UTRC, such as building ventilation, and demonstrated their regenerability for CO2 and formaldehyde, (3) Both partners agree that LACF have potential for possible use in air cleaning applications.

Mechanics of active surfaces

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Salbreux, Guillaume; Jülicher, Frank

2017-09-01

We derive a fully covariant theory of the mechanics of active surfaces. This theory provides a framework for the study of active biological or chemical processes at surfaces, such as the cell cortex, the mechanics of epithelial tissues, or reconstituted active systems on surfaces. We introduce forces and torques acting on a surface, and derive the associated force balance conditions. We show that surfaces with in-plane rotational symmetry can have broken up-down, chiral, or planar-chiral symmetry. We discuss the rate of entropy production in the surface and write linear constitutive relations that satisfy the Onsager relations. We show that the bending modulus, the spontaneous curvature, and the surface tension of a passive surface are renormalized by active terms. Finally, we identify active terms which are not found in a passive theory and discuss examples of shape instabilities that are related to active processes in the surface.

Summary of diamino pyrazoles derived and study their biological activities

International Nuclear Information System (INIS)

Hagui, Marwa

2016-01-01

The work involves the synthesis of new heterocyclic structures diamino pyrazoles derivatives that are present in many natural products and products of pharmacological and therapeutic interests and study their biological activities. In order to develop a radiotracer interest and use in diagnostic nuclear medicine, we are interested to synthesis a pyrazole derivative with the precursor [Re(CO)5Br] and studying the antibacterial and antifungal activity of 3.5-diamino pyrazole and even thioamide complex rhenium. The objectives of our workout: 1/ Synthesis of molecules 3,5-diamino pyrazole and thioamide. 2/ Synthesis of 3,5-diamino pyrazole-rhenium complex. 3/ The in vitro study: Bacteriological Tests (Study of antibacterial and antifungal activity of 3,5-diamino pyrazole and thioamide). The first part of this work concerns the chemical synthesis of molecules such as: thioamide, Amp z1 Ampz2 and then we had synthesized the complex 3,5-diamino pyrazole-rhenium. Similarly we determined the physicochemical characteristics of the compounds synthesized by CLHP, CCM and RMN ( 1 H, 13 C). The second part is devoted to the study in vitro of biological activities of the synthesized molecules and complex 3,5 diaminopyrazole-rhenium with concentration 1 mg/mL and 2 mg/mL. The results allow us to say that the thioamide and Ampz2 have antibacterial activity against S. enterica and Ampz2 has low activity against S. aureus and P. aeruginossa. Other pyrazole derivatives have no significant antibacterial and antifungal activity. The results also show that the synthesized compounds of concentration 2 mg/mL in relation to the inhibition zones of amoxicillin and DMSO: 1/ Escherichia coli, there is antibacterial activity for thioamide, and the Amp z1-Re Ampz2 compound. 2/ Staphylococcus aureus, the complex Ampz 1-Re and the thioamide have significant antibacterial activity. 3/ Salmonella, we observe that the thioamide molecules, Ampz2 and Amp z1-Re have significant antibacterial activity

2-propen-1-amine derivatives and their synthetic intermediates: activity against pathogenic trypanosomatids.

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de Souza, A O; Hemerly, F P; Gomes-Cardoso, L; Santa-Rita, R M; Leon, L L; de Castro, S L; Durán, N

2004-12-01

The potential activity of three new derivatives of 3-(4'-Y-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (2-PAMs) was assayed against Trypanosoma cruzi and Leishmania amazonensis. They showed higher activity against trypomastigotes and epimastigotes of T. cruzi than the standard drugs, crystal violet and nifurtimox. Besides these derivatives, a series of eleven 2-PAMs derivatives and the corresponding intermediates, biphenyl methanones (BPMs) were assayed against promastigotes of L. amazonensis, showing that the 2-PAMs were remarkably more active than the BPMs. The PAMs 2c, 2e and 2j were about 2-fold more active that pentamidine isothionate and between 27.2- and 46.4-fold less toxic to V79 mammalian cells. The present results encourage further studies, especially against intracellular parasites and in experimental animals.

Synthesis and evaluation of the antiplasmodial activity of tryptanthrin derivatives

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Liliane Abodo Onambele

2015-08-01

Full Text Available Malaria remains one of the most deadly diseases threatening humankind and is still affecting a significant proportion of the world population, especially in Africa. Chemotherapy is a vital component of the fight against the disease and new antimalarial agents are urgently needed to curb the spread of malaria parasites that are resistant to existing drugs. The natural product tryptanthrin is known for its wide range of activities, including antiplasmodial activity, but its poor solubility has undermined its development as potent antimicrobial and antiprotozoan agent. The aim of this work was to synthesize analogues of tryptanthrin and to evaluate their antiplasmodial activity against the asexual and sexual blood stages of Plasmodium falciparum. Our results suggest that most tryptanthrin analogues retained their antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30–100 nM. The antiplasmodial activity of the most active compound NT1 (IC50: 30 nM; SI: 155.9 was similar in both strains and close to that of chloroquine (IC50: 20 nM on the sensitive strain. The antiplasmodial activity was improved with derivatization, thus pointing out the necessity to explore tryptanthrin using medicinal chemistry approaches. Ten (10 of the tested derivatives met the criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 < 100 nM. In addition to their activity on the asexual stages, tryptanthrin and two selected derivatives (NT1 and T8 prevented the maturation of gametocytes at their IC90 concentrations, indicating a transmission-blocking potential. Moreover, NT1 was able to impair gametogenesis by reducing the exflagellation of microgametes by 20% at IC90, while tryptanthrin and T8 had no influence on exflagellation. The results of this study confirm that tryptanthrin and its derivatives are potential antimalarial candidates with abilities to kill the

Synthesis of inulin derivatives with quaternary phosphonium salts and their antifungal activity.

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Chen, Yuan; Tan, Wenqiang; Li, Qing; Dong, Fang; Gu, Guodong; Guo, Zhanyong

2018-03-13

Inulin is a kind of renewable and biodegradable carbohydrate with good water solubility and numerous physiological functions. For further utilization of inulin, chemical modification can be applied to improve its bioactivities. In this paper, five novel inulin derivatives were synthesized via chemical modification with quaternary phosphonium salt. Their antifungal activity against three kinds of plant pathogens including Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum was assessed with radial growth assay in vitro. Results revealed that all the inulin derivatives exhibited improved antifungal activity compared with inulin. Particularly, inulin modified with triphenylphosphine (TPhPAIL) exhibited the best antifungal activity with inhibitory indices of 80.0%, 78.8%, and 87.4% against Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum at 1.0mg/mL respectively. The results clearly showed that chemical modification of inulin with quaternary phosphonium salt could efficiently improve derivatives' antifungal activity. Further analysis of results indicated that the antifungal activity was influenced by alkyl chain length or electron-withdrawing ability of the grafted quaternary phosphonium salts. Longer alkyl chain lengths or the stronger electron-withdrawing groups would lead to enhanced antifungal efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

QSAR study of benzimidazole derivatives inhibition on escherichia coli methionine Aminopeptidase

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Zahra Garkani-Nejad

2010-06-01

Full Text Available The paper describes a quantitative structure-activity relationship (QSAR study of IC50 values of benzimidazole derivatives on escherichia coli methionine aminopeptidase. The activity of the 32 inhibitors has been estimated by means of multiple linear regression (MLR and artificial neural network (ANN techniques. The results obtained using the MLR method indicate that the activity of derivatives of benzimidazoles on CoII-loaded escherichia coli methionine aminopeptidase depend on different parameters containing topological descriptors, Burden eigen values, 3D MoRSE descriptors and 2D autocorrelation descriptors. The best artificial neural network model is a fully-connected, feed forward back propagation network with a 5-4-1 architecture. Standard error for the training set using this network was 0.193 with correlation coefficient 0.996 and for the prediction set standard error was 1.41 with correlation coefficient 0.802. Comparison of the quality of the ANN with different MLR models showed that ANN has a better predictive power.

Chemical Synthesis and Biological Activities of Novel Pleuromutilin Derivatives with Substituted Amino Moiety

Science.gov (United States)

Shang, Ruofeng; Wang, Shengyu; Xu, Ximing; Yi, Yunpeng; Guo, Wenzhu; YuLiu; Liang, Jianping

2013-01-01

Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA. PMID:24376551

Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety.

Directory of Open Access Journals (Sweden)

Ruofeng Shang

Full Text Available Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC of 23S rRNA.

The substituent and solvent effects on the antioxidant activity of the ferulic acid derivations

International Nuclear Information System (INIS)

Najafi, M.; Bukhari, S.A.

2014-01-01

The antioxidant activity of ortho and meta substituted ferulic acid derivatives have been investigated in the gas phase and water. The reaction enthalpies of antioxidant activity of studied derivatives have been calculated and compared with corresponding values of ferulic acid. Results show that EWG substituents increase the BDE, IP, while EDG ones cause a rise in the PA. The ferulic acid derivatives with lowest BDE, IP and PA values were identified as the compounds with high antioxidant activity. Results show that the substituents at ortho position have high potential for synthesis of novel ferulic acid derivatives. Results show that ferulic acid derivatives can process their protective role via HAT and SPLET mechanism in gas phase and solvent, respectively. The calculated reaction enthalpies of the substituted ferulic acids have linear dependences with Hammett constants and EHOMO that can be utilized in the selection of suitable substituents for the synthesis of novel antioxidants based on ferulic acid. (author)

Stimulation of Orobanche ramosa seed germination by fusicoccin derivatives: a structure-activity relationship study.

Science.gov (United States)

Evidente, Antonio; Andolfi, Anna; Fiore, Michele; Boari, Angela; Vurro, Maurizio

2006-01-01

A structure-activity relationship study was conducted assaying 25 natural analogues and derivatives of fusicoccin (FC), and cotylenol, the aglycone of cotylenins, for their ability to stimulate the seed germination of the parasitic species Orobanche ramosa. Some of the compounds tested proved to be highly active, being 8,9-isopropylidene of the corresponding FC aglycone and the dideacetyl derivative the most active FC derivatives. In both groups of glucosides and aglycones (including cotylenol), the most important structural feature to impart activity appears to be the presence of the primary hydroxy group at C-19. Furthermore, the functionalities and the conformation of the carbotricyclic ring proved to play a significant role. The dideacetyl derivative of FC, being easily and rapidly obtainable in high yield starting by FC, could be of interest for its practical application as a stimulant of Orobanche ramosa seed germination, inducing the "suicidal germination", an interesting approach for parasitic plant management.

Synthesis, characterization and antibacterial activity of new fluorescent chitosan derivatives

Czech Academy of Sciences Publication Activity Database

Přichystalová, H.; Almonasy, N.; Abdel-Mohsen, A. M.; Abdel-Rahman, R. M.; Fouda, M. M. G.; Vojtova, L.; Kobera, Libor; Spotz, Z.; Burgert, L.; Jancar, J.

2014-01-01

Roč. 65, April (2014), s. 234-240 ISSN 0141-8130 Institutional support: RVO:61389013 Keywords : chitosan derivatives * fluorescence * antibacterial activity Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.858, year: 2014

Antileishmanial Activity of the Hydroalcoholic Extract of Miconia langsdorffii, Isolated Compounds, and Semi-Synthetic Derivatives

Directory of Open Access Journals (Sweden)

Wilson R. Cunha

2011-02-01

Full Text Available The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

Synthesis and pharmacological activity evaluation of arctigenin monoester derivatives.

Science.gov (United States)

Chen, Qiulian; Yang, Limin; Han, Mei; Cai, Enbo; Zhao, Yan

2016-12-01

Arctigenin (ARG), a nature medicine with many pharmacological activities, was poorly soluble in water and placed restriction on practical usage. Six novel arctigenin monoester derivatives were obtained from the reflux reaction with arctigenin, carboxylic acids (crotonic acid, furoic acid, 2-naphthalene acid and indol-3-acetic acid), EDCI and DMAP in dichloromethane at 60°C for 4-6h and their properties on nitrite scavenging assay were investigated in vitro. Based on the results, the one of the most effective derivatives, arctigenin β-indolylacetate (ARG6), was selected to study anti-tumor activity in vivo at doses of 20 and 40mg/kg. The results showed that comparison with ARG group, ARG6 exhibited more anti-tumor activity in H22 tumor-bearing mice. Furthermore, ARG6 exhibited less damage to the liver, kidney, spleen and thymus when compared with those in positive group. Biochemical parameters of ALT, AST, BUN and Cre showed ARG6 had little toxicity to mice as well. ARG6 significantly improved serum cytokine levels of IL-2, IL-6, IFN-γ and TNF-α, and decreased VEGF compared with ARG. Moreover, H & E staining, TUNEL assay and immunohistochemical of tumor issues also indicated that ARG6 exhibited anti-tumor activity in vivo. In brief, the present study provide a method to improve ARG anti-tumor activity and provide a reference for new anti-tumor agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Thrombin-specific inactivation of endothelial cell derived plasminogen activator

Energy Technology Data Exchange (ETDEWEB)

Highsmith, R.F.; Gallaher, M.J.

1986-03-05

Although thrombin (T) has diverse functions in the overall hemostatic mechanism, relatively little is known about its direct effect on components of the fibrinolytic enzyme system. The authors have investigated the interaction of T with plasminogen activators (PA) derived from bovine aortic endothelial cells (EC) in culture (2-5th passage, preconfluent monolayers). Varying concentrations of purified bovine or human thrombin were added to EC-conditioned media (CM). CM + T mixtures were assayed at various times for PA activity using purified plasminogen and a sensitive /sup 125/I-fibrinogenolytic or caseinolytic assay. T (5 nM), but not plasmin or trypsin at equivalent concentrations, resulted in a time-dependent inhibition of the PA activity in CM. T had no effect on the PA activity of urokinase, streptokinase or preformed plasmin. The ability of T to inactivate the EC-derived PA was abolished by prior treatment of T with active site-directed reagents. SDS-PAGE and zymography with copolymerized fibrinogen and plasminogen revealed further specificity in that only one of the multiple-molecular weight forms of PA present in EC-CM was inactivated by T. The authors conclude that in a highly specific fashion, T inactivates the predominant PA present in EC-CM by limited proteolysis. Thus, another potentially important function of T is suggested which may have particular significance in the temporal regulation of coagulation and fibrinolysis at the blood-endothelium interface.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

2010-01-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil

2010-09-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Intrinsically active and pacemaker neurons in pluripotent stem cell-derived neuronal populations.

Science.gov (United States)

Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sébastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

2014-03-11

Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks.

Antimicrobial activity of chemically modified dextran derivatives.

Science.gov (United States)

Tuchilus, Cristina G; Nichifor, Marieta; Mocanu, Georgeta; Stanciu, Magdalena C

2017-04-01

Cationic amphiphilic dextran derivatives with a long alkyl group attached to the reductive end of the polysaccharide chain and quaternary ammonium groups attached as pendent groups to the main dextran backbone were synthesized and tested for their antimicrobial properties against several bacteria and fungi strains. Dependence of antimicrobial activity on both polymer chemical composition (dextran molar mass, length of end alkyl group and chemical structure of ammonium groups) and type of microbes was highlighted by disc-diffusion method (diameter of inhibition zone) and broth microdilution method (minimum inhibitory concentrations). Polymers had antimicrobial activity for all strains studied, except for Pseudomonas aeruginosa ATCC 27853. The best activity against Staphylococcus aureus (Minimun Inhibitory Concentration 60μg/mL) was provided by polymers obtained from dextran with lower molecular mass (Mn=4500), C 12 H 25 or C 18 H 37 end groups, and N,N-dimethyl-N-benzylammonium pendent groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

The road to the first, fully active and more stable human insulin variant with an additional disulfide bond

DEFF Research Database (Denmark)

Vinther, Tine N.; Kjeldsen, Thomas B.; Jensen, Knud Jørgen

2015-01-01

Insulin, a small peptide hormone, is crucial in maintaining blood glucose homeostasis. The stability and activity of the protein is directed by an intricate system involving disulfide bonds to stabilize the active monomeric species and by their non-covalent oligomerization. All known insulin...... variants in vertebrates consist of two peptide chains and have six cysteine residues, which form three disulfide bonds, two of them link the two chains and a third is an intra-chain bond in the A-chain. This classical insulin fold appears to have been conserved over half a billion years of evolution. We...... addressed the question whether a human insulin variant with four disulfide bonds could exist and be fully functional. In this review, we give an overview of the road to engineering four-disulfide bonded insulin analogs. During our journey, we discovered several active four disulfide bonded insulin analogs...

Larvicidal Activity of Essential Oil Derived from Illicium henryi Diels ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research January 2015; 14 (1): 111-116 ... Purpose: To determine larvicidal activity of the essential oil derived from .... males were fed with 10 % glucose solution ... mortality using Abbott's formula [19].

The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

Science.gov (United States)

El-Sayed, Wael M; Hussin, Warda A; Al-Faiyz, Yasair S; Ismail, Mohamed A

2013-09-05

The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models. © 2013 Elsevier B.V. All rights reserved.

Synthesis, antimicrobial and antioxidative activity of some new isatin derivatives

Directory of Open Access Journals (Sweden)

Šekularac Gavrilo M.

2014-01-01

Full Text Available The isatin derivatives, Schiff bases, were synthesized by the reaction of isatin and various substituted primary amines and characterized by several spectroscopic methods. Investigation of the antimicrobial activity of the synthesized compounds was performed by the agar dilution method, against different strains of bacteria and one fungi. The antioxidative activity of the synthesized compounds was also determined. Some of the compounds have shown the significant activity against the selected strains of microorganisms and the antioxidative activity. [Projekat Ministarstva nauke Republike Srbije, br. 172013 i III 46010

A transition from using multi-step procedures to a fully integrated system for performing extracorporeal photopheresis: A comparison of costs and efficiencies.

Science.gov (United States)

Azar, Nabih; Leblond, Veronique; Ouzegdouh, Maya; Button, Paul

2017-12-01

The Pitié Salpêtrière Hospital Hemobiotherapy Department, Paris, France, has been providing extracorporeal photopheresis (ECP) since November 2011, and started using the Therakos ® CELLEX ® fully integrated system in 2012. This report summarizes our single-center experience of transitioning from the use of multi-step ECP procedures to the fully integrated ECP system, considering the capacity and cost implications. The total number of ECP procedures performed 2011-2015 was derived from department records. The time taken to complete a single ECP treatment using a multi-step technique and the fully integrated system at our department was assessed. Resource costs (2014€) were obtained for materials and calculated for personnel time required. Time-driven activity-based costing methods were applied to provide a cost comparison. The number of ECP treatments per year increased from 225 (2012) to 727 (2015). The single multi-step procedure took 270 min compared to 120 min for the fully integrated system. The total calculated per-session cost of performing ECP using the multi-step procedure was greater than with the CELLEX ® system (€1,429.37 and €1,264.70 per treatment, respectively). For hospitals considering a transition from multi-step procedures to fully integrated methods for ECP where cost may be a barrier, time-driven activity-based costing should be utilized to gain a more comprehensive understanding the full benefit that such a transition offers. The example from our department confirmed that there were not just cost and time savings, but that the time efficiencies gained with CELLEX ® allow for more patient treatments per year. © 2017 The Authors Journal of Clinical Apheresis Published by Wiley Periodicals, Inc.

Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives.

Science.gov (United States)

Huang, Mei-Yan; Lin, Jing; Lu, Kuo; Xu, Hong-Gui; Geng, Zhi-Zhong; Sun, Ping-Hua; Chen, Wei-Min

2016-04-13

Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti-inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-α and IL-6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARγ mRNA and protein induced by LPS stimulation. Our results identified the promising anti-inflammatory effects of CSA and its derivatives, which may serve as valuable anti-inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-κB and MAPK pathways, relying partly on resisting the LPS-induced decrease of PPARγ through improving its expression.

Fully unsteady subsonic and supersonic potential aerodynamics for complex aircraft configurations for flutter applications

Science.gov (United States)

Tseng, K.; Morino, L.

1975-01-01

A general theory for study, oscillatory or fully unsteady potential compressible aerodynamics around complex configurations is presented. Using the finite-element method to discretize the space problem, one obtains a set of differential-delay equations in time relating the potential to its normal derivative which is expressed in terms of the generalized coordinates of the structure. For oscillatory flow, the motion consists of sinusoidal oscillations around a steady, subsonic or supersonic flow. For fully unsteady flow, the motion is assumed to consist of constant subsonic or supersonic speed for time t or = 0 and of small perturbations around the steady state for time t 0.

A brief review on activated carbon derived from agriculture by-product

Science.gov (United States)

Yahya, Mohd Adib; Mansor, Muhammad Humaidi; Zolkarnaini, Wan Amani Auji Wan; Rusli, Nurul Shahnim; Aminuddin, Anisah; Mohamad, Khalidah; Sabhan, Fatin Aina Mohamad; Atik, Arif Abdallah Aboubaker; Ozair, Lailatun Nazirah

2018-06-01

A brief review focusing on preparation of the activated carbon derived from agriculture by-products is presented. The physical and chemical activation of activated carbon were also reviewed. The effects of various parameters including types of activating agents, temperature, impregnation ratio, were also discussed. The applications of activated carbon from agricultural by products were briefly reviewed. It is provenly evident in this review, the relatively inexpensive and renewable resources of the agricultural waste were found to be effectively being converted into wealth materials.

Fully convergent chemical synthesis of ester insulin: determination of the high resolution X-ray structure by racemic protein crystallography.

Science.gov (United States)

Avital-Shmilovici, Michal; Mandal, Kalyaneswar; Gates, Zachary P; Phillips, Nelson B; Weiss, Michael A; Kent, Stephen B H

2013-02-27

Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described "ester insulin"--a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond--as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e., [Asp(B10), Lys(B28), Pro(B29)]ester insulin) were prepared by total chemical synthesis. The atomic structure of the synthetic ester insulin molecule was determined by racemic protein X-ray crystallography to a resolution of 1.6 Å. Diffraction quality crystals were readily obtained from the racemic mixture of {D-DKP ester insulin + L-DKP ester insulin}, whereas crystals were not obtained from the L-ester insulin alone even after extensive trials. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin were assayed for receptor binding and in diabetic rats, before and after conversion by saponification to the corresponding DKP insulin enantiomers. L-DKP ester insulin bound weakly to the insulin receptor, while synthetic L-DKP insulin derived from the L-DKP ester insulin intermediate was fully active in binding to the insulin receptor. The D- and L-DKP ester insulins and D-DKP insulin were inactive in lowering blood glucose in diabetic rats, while synthetic L-DKP insulin was fully active in this biological assay. The structural basis of the lack of biological activity of ester insulin is discussed.

Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process.

Science.gov (United States)

George, Meena; Farooq, Masiha; Dang, Thi; Cortes, Bernadette; Liu, Jonathan; Maranga, Luis

2010-08-15

The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production.

Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines

Directory of Open Access Journals (Sweden)

Conor M. Henry

2016-02-01

Full Text Available Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ∼500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis.

SYNTHESIS AND CYTOTOXIC ACTIVITY OF CHALCONE DERIVATIVES ON HUMAN BREAST CANCER CELL LINES

Directory of Open Access Journals (Sweden)

Nuraini Harmastuti

2012-12-01

Full Text Available Chalcone, an α,β-unsaturated ketone, has been shown have many biological activities such as anticancer and antifungi. This research was conducted to synthesize the chalcone derivatives and to obtain their cytotoxic activity on human cervix cancer cell lines. Synthesis of chalcone and its derivatives, 4II-methylchalcone, 4II-methoxychalcone, and 3II,4II-dichlorochalcone was carried out using starting materials of benzaldehide and acetofenon, p-methylacetophenone, p-methoxyacetophenone, as well as m,p-dichloroacetophenone through Claisen Schmidt condensation catalized by NaOH in ethanol at 15 °C. The purity of synthesized compounds were analyzed by thin layer chromatography, melting range, and gas chromatography. Structure elucidations were conducted by UV spectrophotometer, IR spectrometer, 1H-NMR spectrometer, as well as mass spectrometer. Cytotoxic activities were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT microculture tetrazolium viability assay. The results showed that chalcone and derivatives compounds have been able to be synthesized and purified and had the same structure as a predicted structure. Chalcone had highest cytotoxic activity compared to that of its derivatives, with the IC50 values of chalcone, 4II-methylchalcone, 4II-methoxychalcone, and 3II,4II-dichlorochalcone were 9.49, 14.79, 11.48, and 24.26 µg/mL respectively. It was concluded that methyl, methoxy as well as chlorine substitution at 3 II and 4II position decrease the cytotoxic activity of chalcone.

Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

Science.gov (United States)

Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

2016-09-01

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

Phosphorus Determination by Derivative Activation Analysis: A Multifaceted Radiochemical Application.

Science.gov (United States)

Kleppinger, E. W.; And Others

1984-01-01

Although determination of phosphorus is important in biology, physiology, and environmental science, traditional gravimetric and colorimetric methods are cumbersome and lack the requisite sensitivity. Therefore, a derivative activation analysis method is suggested. Background information, procedures, and results are provided. (JN)

Identification of a Recently Active Mammalian SINE Derived from Ribosomal RNA

Science.gov (United States)

Longo, Mark S.; Brown, Judy D.; Zhang, Chu; O’Neill, Michael J.; O’Neill, Rachel J.

2015-01-01

Complex eukaryotic genomes are riddled with repeated sequences whose derivation does not coincide with phylogenetic history and thus is often unknown. Among such sequences, the capacity for transcriptional activity coupled with the adaptive use of reverse transcription can lead to a diverse group of genomic elements across taxa, otherwise known as selfish elements or mobile elements. Short interspersed nuclear elements (SINEs) are nonautonomous mobile elements found in eukaryotic genomes, typically derived from cellular RNAs such as tRNAs, 7SL or 5S rRNA. Here, we identify and characterize a previously unknown SINE derived from the 3′-end of the large ribosomal subunit (LSU or 28S rDNA) and transcribed via RNA polymerase III. This new element, SINE28, is represented in low-copy numbers in the human reference genome assembly, wherein we have identified 27 discrete loci. Phylogenetic analysis indicates these elements have been transpositionally active within primate lineages as recently as 6 MYA while modern humans still carry transcriptionally active copies. Moreover, we have identified SINE28s in all currently available assembled mammalian genome sequences. Phylogenetic comparisons indicate that these elements are frequently rederived from the highly conserved LSU rRNA sequences in a lineage-specific manner. We propose that this element has not been previously recognized as a SINE given its high identity to the canonical LSU, and that SINE28 likely represents one of possibly many unidentified, active transposable elements within mammalian genomes. PMID:25637222

Synthesis and testing of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives for antifungal activity against selected Candida Species

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Cledualdo S. de; Lira, Bruno F.; Athayde-Filho, Petronio F. de, E-mail: athayde-filho@quimica.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Quimica; Barbosa-Filho, Jose M.; Lorenzo, Jorge G.F.; Menezes, Camilla P. de; Santos, Jessyca M.C.G. dos; Lima, Edeltrudes de O. [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Farmaceuticas

2013-01-15

A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones with acetic anhydride and evaluated for their in vitro antifungal activity against six Candida strains: Candida albicans (ATCC 90028 and LM V-42), C. krusei (ATCC 6258 and LM 12 C) and C. tropicalis (ATCC 13803 and LM 14). The Candida strains were found to be sensitive to some of the compounds, which inhibited the growth by 50-90%, with minimum inhibitory concentration (MIC) in the range of 64-512 {mu}g mL{sup -1}. The compounds' structures were fully confirmed and characterized by Fourier transform infrared spectroscopy (FTIR), {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) and mass spectrometry (MS). (author)

Novel haemoglobin-derived antimicrobial peptides from chicken (Gallus gallus) blood: purification, structural aspects and biological activity.

Science.gov (United States)

Vasilchenko, A S; Rogozhin, E A; Vasilchenko, A V; Kartashova, O L; Sycheva, M V

2016-12-01

To purify and characterize antimicrobial peptides derived from the acid extract of Gallus gallus blood cells. Two polypeptides (i.e. CHb-1 and CHb-2) with antibacterial activity were detected in the acidic extract of blood cells from chicken (G. gallus). The isolated peptides that possessed a potent antibacterial activity were purified using a two-step chromatography procedure that involved solid-phase extraction of a total protein/peptide extract followed by thin fractionation by reversed-phase high performance liquid chromatography (RP-HPLC). The molecular masses of the purified peptides were similar and were 4824·4 and 4825·2 Da, which have been measured by matrix-assisted laser desorption/ionization mass spectrometry (MALDI TOF MS). Their amino acid sequences were determined by Edman degradation and showed that the peptides were fully identical to the two fragments of G. gallus α-haemoglobin localized into different subunits (A and D respectively). The peptides were active in micromolar concentrations against Gram-negative Escherichia coli K12 TG1. Using the 1-N-phenylnaphthylamine, the FITC-dextran labelled probes and the live/dead staining allowed to show the hemocidin mode of action and estimate the pore size. In this study, for the first time, α-haemoglobin from chicken (G. gallus) has been investigated as a donor of the two high homologous native peptide fragments that possess potent antibacterial activity in vitro. These are membrane-active peptides and their mechanism of action against E. coli involves a toroidal pore formation. The obtained results expand the perception of the role of haemoglobin in a living system, describing it as a source of multifunction substances. Additionally, the data presented in this paper may contribute to the development of new, cost-effective, antimicrobial agents. © 2016 The Society for Applied Microbiology.

Activation of the aryl hydrocarbon receptor affects activation and function of human monocyte-derived dendritic cells.

Science.gov (United States)

Wang, C; Ye, Z; Kijlstra, A; Zhou, Y; Yang, P

2014-08-01

Aryl hydrocarbon receptor (AhR) is well known for mediating the toxic effects of dioxin-containing pollutants, but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behçet's disease (BD) patients. In this study, we showed that AhR activation by FICZ and ITE down-regulated the expression of co-stimulatory molecules including human leucocyte antigen D-related (HLA-DR), CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. Lipopolysaccharide (LPS)-treated dendritic cells (DCs) from active BD patients showed a higher level of interleukin (IL)-1β, IL-6, IL-23 and tumour necrosis factor (TNF)-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the T helper type 17 (Th17) and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases. © 2014 British Society for Immunology.

Utilization of chemical derivatives in activation analysis

International Nuclear Information System (INIS)

Ehmann, W.D.

1990-01-01

Derivative activation analysis (DAA) is a method to enhance the sensitivity of nuclear activation analysis for the more elusive elements. It may also allow a degree of chemical speciation for the element of interest. DAA uses a preirradiation chemical reaction on the sample to initiate the formation of, or an exchange with, a chemical complex which contains a surrogate element, M. As a result, the amount of the element or the chemical species to be determined, X, is now represented by measurement of the amount of the surrogate element, M, that is made part of, or released by the complex species. The surrogate element is selected for its superior properties for nuclear activation analysis and the absence of interference reaction in its final determination by instrumental neutron activation analysis (INAA) after some preconcentration or separation chemistry. Published DAA studies have been limited to neutron activation analysis. DAA can offer the analyst some important advantages. It can determine elements, functional groups, or chemical species which cannot be determined directly by INAA, fast neutron activation analysis (FNAA), prompt gamma neutron activation analysis (PGNAA), or charged particle activation analysis (CPAA) procedures. When compared with conventional RNAA, there are fewer precautions with respect to handling of intensely radioactive samples, since the chemistry is done before the irradiation. The preirradiation chemistry may also eliminate many interferences that might occur in INAA and, through use of an appropriate surrogate element, can place the analytical gamma-ray line in an interference-free region of the gamma-ray spectrum

Tetherless near-infrared control of brain activity in behaving animals using fully implantable upconversion microdevices.

Science.gov (United States)

Wang, Ying; Lin, Xudong; Chen, Xi; Chen, Xian; Xu, Zhen; Zhang, Wenchong; Liao, Qinghai; Duan, Xin; Wang, Xin; Liu, Ming; Wang, Feng; He, Jufang; Shi, Peng

2017-10-01

Many nanomaterials can be used as sensors or transducers in biomedical research and they form the essential components of transformative novel biotechnologies. In this study, we present an all-optical method for tetherless remote control of neural activity using fully implantable micro-devices based on upconversion technology. Upconversion nanoparticles (UCNPs) were used as transducers to convert near-infrared (NIR) energy to visible light in order to stimulate neurons expressing different opsin proteins. In our setup, UCNPs were packaged in a glass micro-optrode to form an implantable device with superb long-term biocompatibility. We showed that remotely applied NIR illumination is able to reliably trigger spiking activity in rat brains. In combination with a robotic laser projection system, the upconversion-based tetherless neural stimulation technique was implemented to modulate brain activity in various regions, including the striatum, ventral tegmental area, and visual cortex. Using this system, we were able to achieve behavioral conditioning in freely moving animals. Notably, our microscale device was at least one order of magnitude smaller in size (∼100 μm in diameter) and two orders of magnitude lighter in weight (less than 1 mg) than existing wireless optogenetic devices based on light-emitting diodes. This feature allows simultaneous implantation of multiple UCNP-optrodes to achieve modulation of brain function to control complex animal behavior. We believe that this technology not only represents a novel practical application of upconversion nanomaterials, but also opens up new possibilities for remote control of neural activity in the brains of behaving animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

THE STUDY OF HYPOGLYCEMIC ACTIVITY OF 3-BENZYL-8-METHYLXANTHINE DERIVATIVES

Directory of Open Access Journals (Sweden)

I. М. Bilay

2015-04-01

Full Text Available Diabetes mellitus is a chronic endocrine disease. It etiology is the impact of both endogenous (genetic and exogenous factors that cause absolute or relative shortage of insulin or not effective use of it, which in turn leads to disruption of all kinds of substances exchange. The study of this problem is actual due to the high prevalence of diabetes, chronic disease, the tendency to increase the number of patients, their high morbidity and mortality. Diabetes is characterized by high blood glucose levels, which eventually leads to various complications associated with many human systems damage. Hormones (insulin and its analogues and synthetic drugs (sulfonylureas, biguanides etc. are used For the treatment of diabetes, but their high toxicity, cumulativeness, various side effects (autoimmunization, cutaneous allergic reactions, disturbance of the micro flora of the digestive tract, and the formation of insulin resistance restrict the use of these drugs in clinical practice. On this aspect the attention of researchers is attracted to xanthine derivatives, which are known as substances with wide range of biological activities including hypoglycemic. Based on the above, the search and development of new drugs among new 3-R-substituted xanthine, which would have hypoglycemic effect and would be deprived of most side effects is an acute problem of modern medical and pharmaceutical sciences. The aim of this study was to investigate the hypoglycemic activity of newly synthesized derivatives of 3-benzyl-8-methylxanthine and establish certain patterns "structure-activity" relationship. Materials and methods As objects of study for hypoglycemic activity we used derivatives of 3-benzyl-8-methylxanthine synthesized at the Department of Biochemistry and LaboratoryDiagnostics ofZaporizhzhyaStateMedicalUniversity. Hypoglycemic action of xanthine derivatives evaluated by intraperitoneal glucose tolerance test, which was reproduced by injection to animals

Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.

Science.gov (United States)

Ye, Yong-Hao; Ma, Liang; Dai, Zhi-Cheng; Xiao, Yu; Zhang, Ying-Ying; Li, Dong-Dong; Wang, Jian-Xin; Zhu, Hai-Liang

2014-05-07

Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.

Derivation of a regional active-optical reflectance sensor corn algorithm

Science.gov (United States)

Active-optical reflectance sensor (AORS) algorithms developed for in-season corn (Zea mays L.) N management have traditionally been derived using sub-regional scale information. However, studies have shown these previously developed AORS algorithms are not consistently accurate when used on a region...

1,3-Oxazin-6-one Derivatives and Bohemamine-Type Pyrrolizidine Alkaloids from a Marine-Derived Streptomyces spinoverrucosus.

Science.gov (United States)

Fu, Peng; La, Scott; MacMillan, John B

2016-03-25

Two new 1,3-oxazin-6-one derivatives (1 and 2) and six new bohemamine-type pyrrolizidine alkaloids (3-8) were isolated from the marine-derived Streptomyces spinoverrucosus strain SNB-048. Their structures including the absolute configurations were fully elucidated on the basis of spectroscopic analysis, ECD spectra, quantum chemical calculations, and chemical methods. Compounds 1 and 2 possess a γ-lactam moiety and a 1,3-oxazin-6-one system.

Quantitative Structure-Activity Relationship of Insecticidal Activity of Benzyl Ether Diamidine Derivatives

Science.gov (United States)

Zhai, Mengting; Chen, Yan; Li, Jing; Zhou, Jun

2017-12-01

The molecular electrongativity distance vector (MEDV-13) was used to describe the molecular structure of benzyl ether diamidine derivatives in this paper, Based on MEDV-13, The three-parameter (M 3, M 15, M 47) QSAR model of insecticidal activity (pIC 50) for 60 benzyl ether diamidine derivatives was constructed by leaps-and-bounds regression (LBR) . The traditional correlation coefficient (R) and the cross-validation correlation coefficient (R CV ) were 0.975 and 0.971, respectively. The robustness of the regression model was validated by Jackknife method, the correlation coefficient R were between 0.971 and 0.983. Meanwhile, the independent variables in the model were tested to be no autocorrelation. The regression results indicate that the model has good robust and predictive capabilities. The research would provide theoretical guidance for the development of new generation of anti African trypanosomiasis drugs with efficiency and low toxicity.

Non-Linear Back-propagation: Doing Back-Propagation withoutDerivatives of the Activation Function

DEFF Research Database (Denmark)

Hertz, John; Krogh, Anders Stærmose; Lautrup, Benny

1997-01-01

The conventional linear back-propagation algorithm is replaced by a non-linear version, which avoids the necessity for calculating the derivative of the activation function. This may be exploited in hardware realizations of neural processors. In this paper we derive the non-linear back...

Sulfonamide and carbamate derivatives of 6-chloropurine: synthesis, characterization and antimicrobial activity evaluation

Directory of Open Access Journals (Sweden)

K. Venkata Narayana

2016-07-01

Full Text Available A series of new sulfonamide derivatives, 9-(substitutedbenzenesulfonyl-6-chloro-9H-purines 7(a-e and carbamate derivatives, 6-chloro-purine-9-carboxylic acid substituted alkyl/arylester 9(a-d, have been synthesized through an intermediate, sodium salt of 6-chloro-9(H-purine (6 which was prepared by the treatment of 6-chloro-9(H-purine (4 with sodium hydride. Structures of the newly synthesized compounds were elucidated by IR, NMR ( 1H and 13C, mass spectra and elemental analysis. Antimicrobial activity against three bacterial strains and three fungal strains at two different concentrations, 100 and 200 µg/mL including MIC values was investigated. Bio-screening data disclosed that most of the sulfonamide derivatives, 7a, 7c and 7d, and one carbamate derivative 9a showed promising antimicrobial activity having MIC values in the range of 18.0-25.0 µg/mL.

Haemolytic activity of uranium compounds haemolysis by thermochemical derivatives of ammonium uranate

International Nuclear Information System (INIS)

Stuart, W.I.; Tucker, A.D.; Adams, R.B.

1975-01-01

A study has been made of the haemolytic action on human erythrocytes by ammonium uranate (AU) and various thermochemical products of AU. These products were obtained by heating AU in hydrogen at 5 0 C min -1 to various temperatures. Haemolysis has been interpreted in terms of a diffusion model which for each product yields a single parameter Ksub(N), the haemolytic activity factor. The magnitude of Ksub(N) is a convenient measure of the ability of a powder to damage erythrocytes. The haemolytic activity of certain thermochemical derivatives indicates an exceptionally high potential for damage to erythrocytes. Infrared and thermoanalytical measurements have shown that the high activity of these products derives principally from a self-reduction reaction, induced by heating AU to 400-420 0 C in hydrogen. (author)

Propagation of electromagnetic waves in a weak collisional and fully ionized dusty plasma

Energy Technology Data Exchange (ETDEWEB)

Jia, Jieshu; Yuan, Chengxun, E-mail: yuancx@hit.edu.cn; Gao, Ruilin; Wang, Ying; Zhou, Zhong-Xiang [Department of Physics, Harbin Institute of Technology, Harbin 150001 (China); Liu, Sha; Yue, Feng [Shanghai Institute of Spaceflight Control Technology, Shanghai 200233 (China); Wu, Jian [China Research Institute of Radio wave Propagation, Beijing 102206 (China); Li, Hui [Department of Physics, Harbin Institute of Technology, Harbin 150001 (China); China Research Institute of Radio wave Propagation, Beijing 102206 (China)

2016-04-15

The propagation properties of electromagnetic (EM) waves in fully ionized dusty plasmas is the subject of this study. The dielectric relationships for EM waves propagating in a fully ionized dusty plasma was derived from the Boltzmann distribution law, taking into consideration the collision and charging effects of the dust grains. The propagation properties of the EM waves in a dusty plasma were numerically calculated and studied. The study results indicated that the dusty grains with an increased radius and charge were more likely to impede the penetration of EM waves. Dust grains with large radii and high charge cause the attenuation of the EM wave in the dusty plasma. The different density of the dust in the plasma appeared to have no obvious effect on the transmission of the EM waves. The propagation of the EM waves in a weakly ionized dusty plasma varies from that in a fully ionized dusty plasma. The results are helpful to analyze the effects of dust in dusty plasmas and also provide a theoretical basis for future studies.

Propagation of electromagnetic waves in a weak collisional and fully ionized dusty plasma

International Nuclear Information System (INIS)

Jia, Jieshu; Yuan, Chengxun; Gao, Ruilin; Wang, Ying; Zhou, Zhong-Xiang; Liu, Sha; Yue, Feng; Wu, Jian; Li, Hui

2016-01-01

The propagation properties of electromagnetic (EM) waves in fully ionized dusty plasmas is the subject of this study. The dielectric relationships for EM waves propagating in a fully ionized dusty plasma was derived from the Boltzmann distribution law, taking into consideration the collision and charging effects of the dust grains. The propagation properties of the EM waves in a dusty plasma were numerically calculated and studied. The study results indicated that the dusty grains with an increased radius and charge were more likely to impede the penetration of EM waves. Dust grains with large radii and high charge cause the attenuation of the EM wave in the dusty plasma. The different density of the dust in the plasma appeared to have no obvious effect on the transmission of the EM waves. The propagation of the EM waves in a weakly ionized dusty plasma varies from that in a fully ionized dusty plasma. The results are helpful to analyze the effects of dust in dusty plasmas and also provide a theoretical basis for future studies.

Synthesis and proapoptotic activity of oleanolic acid derived amides.

Science.gov (United States)

Heller, Lucie; Knorrscheidt, Anja; Flemming, Franziska; Wiemann, Jana; Sommerwerk, Sven; Pavel, Ioana Z; Al-Harrasi, Ahmed; Csuk, René

2016-10-01

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14-16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines.

Science.gov (United States)

Henry, Conor M; Sullivan, Graeme P; Clancy, Danielle M; Afonina, Inna S; Kulms, Dagmar; Martin, Seamus J

2016-02-02

Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ~500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The production of fully deacetylated chitosan by compression method

Directory of Open Access Journals (Sweden)

Xiaofei He

2016-03-01

Full Text Available Chitosan’s activities are significantly affected by degree of deacetylation (DDA, while fully deacetylated chitosan is difficult to produce in a large scale. Therefore, this paper introduces a compression method for preparing 100% deacetylated chitosan with less environmental pollution. The product is characterized by XRD, FT-IR, UV and HPLC. The 100% fully deacetylated chitosan is produced in low-concentration alkali and high-pressure conditions, which only requires 15% alkali solution and 1:10 chitosan powder to NaOH solution ratio under 0.11–0.12 MPa for 120 min. When the alkali concentration varied from 5% to 15%, the chitosan with ultra-high DDA value (up to 95% is produced.

Mast cells enhance T cell activation: Importance of mast cell-derived TNF

Science.gov (United States)

Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

2005-05-01

Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response

Synthesis and Analgesic Activity Evaluation of Some Agmatine Derivatives

Directory of Open Access Journals (Sweden)

Song Li

2006-06-01

Full Text Available A series of N,N’-disubstituted-2-nitroethene-1,1-diamine and N,N’-disubstituted- N’’-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these compounds might be developed for treatment of opioid tolerance and dependence.

Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

Energy Technology Data Exchange (ETDEWEB)

Silva, M.S.S.; Lima, S.G. de; Lopes, J.A.D.; Chaves, M.H.; Cito, A.M.G.L. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Quimica]. E-mail: gracito@ufpi.br; Oliveira, E.H. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Microbiologia e Parasitologia; Reis, F.A.M. [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Inst. de Quimica

2008-07-01

Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by {sup 1}H and {sup 13}C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), mono ene anacardic acid (3), alpha-amirine (4), beta-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp. (author)

Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

International Nuclear Information System (INIS)

Silva, M.S.S.; Lima, S.G. de; Lopes, J.A.D.; Chaves, M.H.; Cito, A.M.G.L.; Oliveira, E.H.; Reis, F.A.M.

2008-01-01

Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by 1 H and 13 C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), mono ene anacardic acid (3), alpha-amirine (4), beta-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp. (author)

Cobalt-embedded carbon nanofiber derived from a coordination polymer as a highly efficient heterogeneous catalyst for activating oxone in water.

Science.gov (United States)

Lin, Kun-Yi Andrew; Tong, Wai-Chi; Du, Yunchen

2018-03-01

Carbon fiber (CF) supported cobalt nanoparticles (NPs) are promising catalysts for activating Oxone because carbon is non-metal and earth-abundant, and CF-based catalysts exhibit a high aspect ratio, which affords more accessible and dense catalytic sites. Nevertheless, most of CF-supported catalysts are fabricated by post-synthetic methods, which involve complicated preparations. More importantly, metallic NPs are attached to the outer surface of CF rather than embedded within CF. However, there is still a great demand for developing Co-bearing carbon fibers for Oxone activation via simple and effective methods. Thus, this study proposes to develop a cobalt NP-embedded carbon nanofiber (CCNF) by a simple hydrothermal reaction of Co and nitrilotriacetic acid (NA), followed by one-step carbonization. Owing to the coordinative structure of CoNA, the derivative CCNF exhibits a fibrous carbon matrix embedded with evenly distributed and densely packed Co 3 O 4 and magnetic Co 0 nanoparticles. The fibrous structure, magnetism and embedded Co NPs enable CCNF to be a promising catalyst for Oxone activation. As degradation of Rhodamine B (RhB) is selected as a model reaction, CCNF not only rapidly activates Oxone to fully degrade RhB but also shows a much higher catalytic activity than the most common Oxone activator, Co 3 O 4 . CCNF also exhibits the lowest activation energy than any reported catalysts for Oxone activation to degrade RhB. In addition, CCNF could be re-used to activate Oxone for RhB degradation. These results indicate that CCNF is a conveniently prepared and highly effective fibrous Co/C hybrid material for activating Oxone to oxidize contaminants in water. Copyright © 2017. Published by Elsevier Ltd.

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

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Nafiz Öncü Can

2018-03-01

Full Text Available Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR, 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR, 13C Nuclear Magnetic Resonance Spectroscopy (13C-NMR and Electronspray Ionisation Mass Spectroscopy (ESI-MS spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST and modified forced swimming (MFST methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

Syntehsis and antiproliferative activities of chloropyridazine derivatives retain alkylsulfonyl moiety

Energy Technology Data Exchange (ETDEWEB)

Kim, Chae Won; Park, Myung Sook [College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of)

2016-11-15

Some chloropyridazine derivatives have shown interesting pharmacodynamics properties in terms of antioxidant and anti-human rotavirus (HRV) activities (Figure 1). To date, however, no study has evaluated the antiproliferative effects of chloropyridazines in other types of human cancer cells. In conclusion, we designed and synthesized a total of five groups of alkoxy-(or alkylthio-, alkylselenyl-, alkylsufinyl alkylsulfonyl-)chloropyridazines, and their antiproliferative activity was evaluated in the human cancer cell lines. IC{sub 50} values showed that the alkylsulfonylchloropyridazine compounds exhibited more active than the other four groups having alkoxy, alkylthio, alkylselenyl, alkylsulfinyl moieties against MCF-7 and Hep2B Cells.

Syntehsis and antiproliferative activities of chloropyridazine derivatives retain alkylsulfonyl moiety

International Nuclear Information System (INIS)

Kim, Chae Won; Park, Myung Sook

2016-01-01

Some chloropyridazine derivatives have shown interesting pharmacodynamics properties in terms of antioxidant and anti-human rotavirus (HRV) activities (Figure 1). To date, however, no study has evaluated the antiproliferative effects of chloropyridazines in other types of human cancer cells. In conclusion, we designed and synthesized a total of five groups of alkoxy-(or alkylthio-, alkylselenyl-, alkylsufinyl alkylsulfonyl-)chloropyridazines, and their antiproliferative activity was evaluated in the human cancer cell lines. IC_5_0 values showed that the alkylsulfonylchloropyridazine compounds exhibited more active than the other four groups having alkoxy, alkylthio, alkylselenyl, alkylsulfinyl moieties against MCF-7 and Hep2B Cells

Synthesis and fungicidal activity of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline.

Science.gov (United States)

Lei, Peng; Zhang, Xuebo; Xu, Yan; Xu, Gaofei; Liu, Xili; Yang, Xinling; Zhang, Xiaohe; Ling, Yun

2016-01-01

Take-all of wheat, caused by the soil-borne fungus Gaeumannomyces graminis var. tritici, is one of the most important and widespread root diseases. Given that take-all is still hard to control, it is necessary to develop new effective agrochemicals. Pyrazole derivatives have been often reported for their favorable bioactivities. In order to discover compounds with high fungicidal activity and simple structures, 1,2,3,4-tetrahydroquinoline, a biologically active group of natural products, was introduced to pyrazole structure. A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized, and their fungicidal activities were evaluated. The bioassay results demonstrated that the title compounds displayed obvious fungicidal activities at a concentration of 50 μg/mL, especially against V. mali, S. sclerotiorum and G. graminis var. tritici. The inhibition rates of compounds 10d, 10e, 10h, 10i and 10j against G. graminis var. tritici were all above 90 %. Even at a lower concentration of 16.7 μg/mL, compounds 10d and 10e exhibited satisfied activities of 100 % and 94.0 %, respectively. It is comparable to that of the positive control pyraclostrobin with 100 % inhibition rate. A series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were synthesized and their structures were confirmed by (1)H NMR, (13)C NMR, IR spectrum and HRMS or elemental analysis. The crystal structure of compound 10g was confirmed by X-ray diffraction. Bioassay results indicated that all title compounds exhibited obvious fungicidal activities. In particular, compounds 10d and 10e showed comparable activities against G. graminis var. tritici with the commercial fungicide pyraclostrobin at the concentration of 16.7 μg/mL.Graphical abstractA series of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline were designed and synthesized. Bioassay results indicated that all these compounds exhibited obvious fungicidal activities.

Synthesis, characterization and biological activity of C6-Schiff bases derivatives of chitosan.

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Xu, Ruibo; Aotegen, Bayaer; Zhong, Zhimei

2017-12-01

C 6 -Schiff bases derivatives of chitosan were synthesized for the first time. C 2 -amino groups and C 3 -hydroxy groups were firstly protected by CuSO 4 ·5H 2 O, and the C 6 -hydroxy was then transformed into aldehyde, which then reacted with anilines through nucleophilic addition to introduce the CN group at C 6 -position in chitosan chain. Finally, C 6 -Schiff bases derivatives of chitosan were got by the deprotection of C 2 -NH 2 with cation exchange resin. The structures and properties of the new synthesized products were characterized by Fourier transform infrared spectroscopy, 13 C NMR, SEM image, and elemental analysis. The antibacterial activities of derivatives were tested in the experiment, and the results showed that the prepared chitosan derivatives had significantly improved antibacterial activity toward Staphylococcus aureus and Escherichia coli. The Cytotoxicity test showed that the prepared chitosan derivatives had low Cytotoxicity, compared with chitosan and C 2 -benzaldehyde Schiff bases of chitosan. This paper allowed a new method for the synthesis of Schiff bases of chitosan, which was enlightening. Copyright © 2017 Elsevier B.V. All rights reserved.

Aloe vera Derived Activated High-Surface-Area Carbon for Flexible and High-Energy Supercapacitors.

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Karnan, M; Subramani, K; Sudhan, N; Ilayaraja, N; Sathish, M

2016-12-28

Materials which possess high specific capacitance in device configuration with low cost are essential for viable application in supercapacitors. Herein, a flexible high-energy supercapacitor device was fabricated using porous activated high-surface-area carbon derived from aloe leaf (Aloe vera) as a precursor. The A. vera derived activated carbon showed mesoporous nature with high specific surface area of ∼1890 m 2 /g. A high specific capacitance of 410 and 306 F/g was achieved in three-electrode and symmetric two-electrode system configurations in aqueous electrolyte, respectively. The fabricated all-solid-state device showed a high specific capacitance of 244 F/g with an energy density of 8.6 Wh/kg. In an ionic liquid electrolyte, the fabricated device showed a high specific capacitance of 126 F/g and a wide potential window up to 3 V, which results in a high energy density of 40 Wh/kg. Furthermore, it was observed that the activation temperature has significant role in the electrochemical performance, as the activated sample at 700 °C showed best activity than the samples activated at 600 and 800 °C. The electron microscopic images (FE-SEM and HR-TEM) confirmed the formation of pores by the chemical activation. A fabricated supercapacitor device in ionic liquid with 3 V could power up a red LED for 30 min upon charging for 20s. Also, it is shown that the operation voltage and capacitance of flexible all-solid-state symmetric supercapacitors fabricated using aloe-derived activated carbon could be easily tuned by series and parallel combinations. The performance of fabricated supercapacitor devices using A. vera derived activated carbon in all-solid-state and ionic liquid indicates their viable applications in flexible devices and energy storage.

Structural analysis and antimicrobial activity of 2[1H]-pyrimidinethione/selenone derivatives

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Żesławska, Ewa; Korona-Głowniak, Izabela; Szczesio, Małgorzata; Olczak, Andrzej; Żylewska, Alicja; Tejchman, Waldemar; Malm, Anna

2017-08-01

Four new crystal structures of sulfur and selenium analogues of 2[1H]-pyrimidinone derivatives were determined with the use of X-ray diffraction method. The molecular geometry and intermolecular interactions of the investigated molecules were analyzed in order to find the structural features and geometrical parameters, which can be responsible for antimicrobial activities. The influence of chalcogen substituents (sulfur and selenium) on the crystal packing was also studied. The main differences in the molecular structures exist in mutual arrangement of two aromatic rings. The intermolecular interactions in all investigated compounds are similar. Furthermore, the in vitro antibacterial and antifungal activities for these compounds were evaluated. Preliminary investigations have identified two highly potent antibacterial compounds containing selenium atom, which display selectivity towards staphylococci and micrococci. This selectivity was not observed for a control compound used as a drug, namely vancomycin. These compounds possess also good antifungal activity. This is the first report of biological activities of 2[1H]-pyrimidineselenone derivatives.

A multiscale finite element method for modeling fully coupled thermomechanical problems in solids

KAUST Repository

Sengupta, Arkaprabha; Papadopoulos, Panayiotis; Taylor, Robert L.

2012-01-01

This article proposes a two-scale formulation of fully coupled continuum thermomechanics using the finite element method at both scales. A monolithic approach is adopted in the solution of the momentum and energy equations. An efficient implementation of the resulting algorithm is derived that is suitable for multicore processing. The proposed method is applied with success to a strongly coupled problem involving shape-memory alloys. © 2012 John Wiley & Sons, Ltd.

A multiscale finite element method for modeling fully coupled thermomechanical problems in solids

KAUST Repository

Sengupta, Arkaprabha

2012-05-18

This article proposes a two-scale formulation of fully coupled continuum thermomechanics using the finite element method at both scales. A monolithic approach is adopted in the solution of the momentum and energy equations. An efficient implementation of the resulting algorithm is derived that is suitable for multicore processing. The proposed method is applied with success to a strongly coupled problem involving shape-memory alloys. © 2012 John Wiley & Sons, Ltd.

Antibacterial activity of cobalt(II complexes with some benzimidazole derivatives

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S. O. PODUNAVAC-KUZMANOVIC

2008-12-01

Full Text Available The antibacterial activities of cobalt(II complexes with two series of benzimidazoles were evaluated in vitro against three Gram-positive bacterial strains (Bacillus cereus, Staphylococcus aureus, and Sarcina lutea and one Gram-negative isolate (Pseudomonas aeruginosa. The minimum inhibitory concentration was determined for all the complexes. The majority of the investtigated complexes displayed in vitro inhibitory activity against very persistent bacteria. They were found to be more active against Gram-positive than Gram-negative bacteria. It may be concluded that the antibacterial activity of the compounds is related to the cell wall structure of the tested bacteria. Comparing the inhibitory activities of the tested complexes, it was found that the 1-substituted-2-aminobenzimidazole derivatives were more active than complexes of 1-substituted-2-amino-5,6-dimethylbenzimidazoles. The effect of chemical structure on the antibacterial activity is discussed.

Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

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Siebler Mario

2009-08-01

Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

76 FR 36176 - Fully Developed Claim (Fully Developed Claims-Applications for Compensation, Pension, DIC, Death...

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2011-06-21

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-0747] Fully Developed Claim (Fully Developed Claims--Applications for Compensation, Pension, DIC, Death Pension, and/or Accrued Benefits); Correction AGENCY: Veterans Benefits Administration, Department of Veterans Affairs. ACTION: Notice; correction...

Disubstituted thiourea derivatives and their activity on CNS: synthesis and biological evaluation.

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Stefanska, Joanna; Szulczyk, Daniel; Koziol, Anna E; Miroslaw, Barbara; Kedzierska, Ewa; Fidecka, Sylwia; Busonera, Bernardetta; Sanna, Giuseppina; Giliberti, Gabriele; La Colla, Paolo; Struga, Marta

2012-09-01

A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The (1)H NMR, (13)C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against gram-positive cocci, gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1-13) were examined for cytotoxicity, antitumor, and anti-HIV activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Antibacterial activity of 3-methylbenzo[d]thiazol-methylquinolinium derivatives and study of their action mechanism.

Science.gov (United States)

Sun, Ning; Du, Ruo-Lan; Zheng, Yuan-Yuan; Guo, Qi; Cai, Sen-Yuan; Liu, Zhi-Hua; Fang, Zhi-Yuan; Yuan, Wen-Chang; Liu, Ting; Li, Xiao-Mei; Lu, Yu-Jing; Wong, Kwok-Yin

2018-12-01

The increasing incidence of multidrug resistant bacterial infection renders an urgent need for the development of new antibiotics. To develop small molecules disturbing FtsZ activity has been recognized as promising approach to search for antibacterial of high potency systematically. Herein, a series of novel quinolinium derivatives were synthesized and their antibacterial activities were investigated. The compounds show strong antibacterial activities against different bacteria strains including MRSA, VRE and NDM-1 Escherichia coli. Among these derivatives, a compound bearing a 4-fluorophenyl group (A2) exhibited a superior antibacterial activity and its MICs to the drug-resistant strains are found lower than those of methicillin and vancomycin. The biological results suggest that these quinolinium derivatives can disrupt the GTPase activity and dynamic assembly of FtsZ, and thus inhibit bacterial cell division and then cause bacterial cell death. These compounds deserve further evaluation for the development of new antibacterial agents targeting FtsZ.

Synthesis and Analgesic Activity of Novel Derivatives of 1,2-Substituted Benzimidazoles

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Shobhit Srivastava

2013-01-01

Full Text Available A series of novel 2-phenylhydrazinomethyl and 2-(2-hydroxyphenyl-benzimidazole derivatives substituted at the N1-position of benzimidazole nucleus were synthesized as well as screened for analgesic activity. Some of these compounds showed promising analgesic activity when compared with the standard drug diclofenac sodium. The incorporation of a phenylhydrazinomethyl nucleus at 2-position of benzimidazole compound gave a biologically active pharmacophore.

Antifungal activity of topical microemulsion containing a thiophene derivative

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Geovani Pereira Guimarães

2014-06-01

Full Text Available Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05 embedded in a microemulsion (ME. The minimum inhibitory concentration (MIC was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05 showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 µg.mL-1 and good activity against C. neoformans (MIC = 17 µg.mL-1. Candida species were susceptible to ME-5CN05 (70-140 µg.mL-1, but C. neoformans was much more, presenting a MIC value of 2.2 µg.mL-1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.

Pharmacological Activities and Synthesis of Esculetin and Its Derivatives: A Mini-Review

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Chengyuan Liang

2017-03-01

Full Text Available Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine Cortex Fraxini. The twig skin or trunk bark of Cortex Fraxini are used by herb doctors as a mild, bitter liver and gallbladder meridians’ nontoxic drug as well as dietary supplement. Recently, with a variety of novel esculetin derivatives being reported, the molecular mechanism research as well as clinical application of Cortex Fraxini and esculetin are becoming more attractive. This mini-review will consolidate what is known about the biological activities, the mechanism of esculetin and its synthetic derivatives over the past decade in addition to providing a brief synopsis of the properties of esculetin.

The effect of lipophilicity on the antibacterial activity of some 1-benzylbenzimidazole derivatives

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D. J. BARNA

2008-10-01

Full Text Available In the present paper, the antibacterial activity of some 1-benzylbenzimidazole derivatives were evaluated against the Gram-negative bacteria Escherichia coli. The minimum inhibitory concentration was determined for all the compounds. Quantitative structure–activity relationship (QSAR was employed to study the effect of the lipophilicity parameters (log P on the inhibitory activity. Log P values for the target compounds were experimentally determined by the “shake-flask” method and calculated by using eight different software products. Multiple linear regression was used to correlate the log P values and antibacterial activity of the studied benzimidazole derivatives. The results are discussed based on statistical data. The most acceptable QSAR models for the prediction of the antibacterial activity of the investigated series of benzimidazoles were developed. High agreement between the experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on the antibacterial activity of this class of compounds, which simplifies the design of new biologically active molecules.

Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic Activity of Cell-Derived Microparticles.

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Briens, Aurélien; Gauberti, Maxime; Parcq, Jérôme; Montaner, Joan; Vivien, Denis; Martinez de Lizarrondo, Sara

2016-01-01

Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu. They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells. Although detection and characterization of cell-derived MPs may be of high diagnostic and prognostic values in a number of human diseases, reliable measurement of their size, number and biological activity still remains challenging using currently available methods. In the present study, we developed a protocol to directly image and functionally characterize MPs using high-resolution laser-scanning confocal microscopy. Once trapped on annexin-V coated micro-wells, we developed several assays using fluorescent reporters to measure their size, detect membrane antigens and evaluate proteolytic activity (nano-zymography). In particular, we demonstrated the applicability and specificity of this method to detect antigens and proteolytic activities of tissue-type plasminogen activator (tPA), urokinase and plasmin at the surface of engineered MPs from transfected cell-lines. Furthermore, we were able to identify a subset of tPA-bearing fibrinolytic MPs using plasma samples from a cohort of ischemic stroke patients who received thrombolytic therapy and in an experimental model of thrombin-induced ischemic stroke in mice. Overall, this method is promising for functional characterization of cell-derived MPs.

Formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations - A review.

Science.gov (United States)

Zhao, Cindy J; Schieber, Andreas; Gänzle, Michael G

2016-11-01

Fermented foods are valued for their rich and complex odour and taste. The metabolic activity of food-fermenting microorganisms determines food quality and generates odour and taste compounds. This communication reviews the formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations. Pathways of the generation of taste compounds are presented for soy sauce, cheese, fermented meats, and bread. Proteolysis or autolysis during food fermentations generates taste-active amino acids and peptides; peptides derived from proteolysis particularly impart umami taste (e.g. α-glutamyl peptides) or bitter taste (e.g. hydrophobic peptides containing proline). Taste active peptide derivatives include pyroglutamyl peptides, γ-glutamyl peptides, and succinyl- or lactoyl amino acids. The influence of fermentation microbiota on proteolysis, and peptide hydrolysis, and the metabolism of glutamate and arginine is well understood, however, the understanding of microbial metabolic activities related to the formation of taste-active peptide derivatives is incomplete. Improved knowledge of the interactions between taste-active compounds will enable the development of novel fermentation strategies to develop tastier, less bitter, and low-salt food products, and may provide novel and "clean label" ingredients to improve the taste of other food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

International Nuclear Information System (INIS)

Borgati, Thiago F.; Alves, Rosemeire B.

2013-01-01

Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10 -4 mol L -1 . Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

Synthesis and antiproliferative activity of novel polynuclear heterocyclic compounds derived from 2,3-diaminophenazine.

Science.gov (United States)

Mahran, Asma M; Ragab, Sherif Sh; Hashem, Ahmed I; Ali, Mamdouh M; Nada, Afaf A

2015-01-27

2,3-Diaminophenazine 1 was used as a precursor for the preparation of some novel phenazine derivatives such as imidazo[4,5-b]phenazine-2-thione 2, its methylthio 3, ethyl 1-aryl-3H-[1,2,4]triazolo[2,3-a]imidazo[4,5-b]phenazines 8a-c, ethyl (2Z)-[3-aminophenazin-2-yl)amino](phenylhydrazono)ethanoate 9, pyrazino[2,3-b]phenazine derivatives 10, 12, 15-17, [1,4]diazepino[2,3-b]phenazine derivatives 13, 14, 2,3-dibenzoylaminophenazine 18, 1H-Imidazo[4,5-b]phenazine derivatives 20, 23a-c, 24, 25 and 4-[(E)-(3-amino phenazin-2-yl)diazenyl] derivatives 27-29. All compounds were tested as inhibitors of the proliferation of human lung carcinoma and colorectal cancer cell lines through inhibition of Tyrosine Kinases. Most of compounds exert good activity against the two cancer cell lines. Five compounds (1, 2, 3, 25 and 28) were found to possess the same activity as the standard drug Cisplatin. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Synthesis and antimycobacterial activity of isoniazid derivatives from renewable fatty acids.

Science.gov (United States)

Rodrigues, Marieli O; Cantos, Jéssica B; D'Oca, Caroline R Montes; Soares, Karina L; Coelho, Tatiane S; Piovesan, Luciana A; Russowsky, Dennis; da Silva, Pedro A; D'Oca, Marcelo G Montes

2013-11-15

This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adsorption of ultra-low concentration malodorous substances using coal-derived granular activated carbons

Energy Technology Data Exchange (ETDEWEB)

Urano, K.; Maeda, T.; Yamashita, H.; Hagio, S.; Arioka, A.

1986-01-01

The experimental adsorption is reported of diosmin and 2-methylisoborneol using two types of coal-derived granular activated carbon and one derived from coconut husk. It was discovered that carbons with more pores below 15 angstroms in size gave a higher equilibrium adsorption of malodorous substances at mg/l concentrations. It was also found that the coal-derived materials, which contained more pores larger than 15 angstroms, gave faster adsorption. Given that the coal-derived carbons have a longer service life, it is concluded that they are suitable for use in full-scale adsorption plant where contact times are short. 3 references, 5 figures, 5 tables.

Wastewater treatment using low cost activated carbons derived from agricultural byproducts-A case study

Energy Technology Data Exchange (ETDEWEB)

Mohan, Dinesh [Environmental Chemistry Division, Industrial Toxicology Research Centre, Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001, U.P. (India)], E-mail: dm_1967@hotmail.com; Singh, Kunwar P.; Singh, Vinod K. [Environmental Chemistry Division, Industrial Toxicology Research Centre, Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001, U.P. (India)

2008-04-15

A variety of low cost activated carbons were developed from agricultural waste materials viz., coconut shell, coconut shell fibers and rice husk. The low cost activated carbons were fully characterized and utilized for the remediation of various pollutants viz., chemical oxygen demand (COD), heavy metals, anions, etc., from industrial wastewater. Sorption studies were carried out at different temperatures and particle sizes to study the effect of temperatures and surface areas. The removal of chloride and fluoride increased with rise in temperature while COD and metal ions removal decreased with increase in temperature, thereby, indicating the processes to be endothermic and exothermic, respectively. The kinetics of COD adsorption was also carried out at different temperatures to establish the sorption mechanism and to determine various kinetic parameters. The COD removal was 47-72% by coconut shell fiber carbon (ATFAC), 50-74% by coconut shell carbon (ATSAC) and 45-73% by rice husk carbon (ATRHC). Furthermore, COD removal kinetics by rice husk carbon, coconut shell carbon and coconut fiber carbon at different temperatures was approximately represented by a first order rate law. Results of this fundamental study demonstrate the effectiveness and feasibility of low cost activated carbons. The parameters obtained in this study can be fully utilized to establish fixed bed reactors on large scale to treat the contaminated water.

Wastewater treatment using low cost activated carbons derived from agricultural byproducts-A case study

International Nuclear Information System (INIS)

Mohan, Dinesh; Singh, Kunwar P.; Singh, Vinod K.

2008-01-01

A variety of low cost activated carbons were developed from agricultural waste materials viz., coconut shell, coconut shell fibers and rice husk. The low cost activated carbons were fully characterized and utilized for the remediation of various pollutants viz., chemical oxygen demand (COD), heavy metals, anions, etc., from industrial wastewater. Sorption studies were carried out at different temperatures and particle sizes to study the effect of temperatures and surface areas. The removal of chloride and fluoride increased with rise in temperature while COD and metal ions removal decreased with increase in temperature, thereby, indicating the processes to be endothermic and exothermic, respectively. The kinetics of COD adsorption was also carried out at different temperatures to establish the sorption mechanism and to determine various kinetic parameters. The COD removal was 47-72% by coconut shell fiber carbon (ATFAC), 50-74% by coconut shell carbon (ATSAC) and 45-73% by rice husk carbon (ATRHC). Furthermore, COD removal kinetics by rice husk carbon, coconut shell carbon and coconut fiber carbon at different temperatures was approximately represented by a first order rate law. Results of this fundamental study demonstrate the effectiveness and feasibility of low cost activated carbons. The parameters obtained in this study can be fully utilized to establish fixed bed reactors on large scale to treat the contaminated water

Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives

Energy Technology Data Exchange (ETDEWEB)

Barros, Francisco W.A. [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil); Bezerra, Daniel P., E-mail: danielpbezerra@gmail.com [Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe (Brazil); Ferreira, Paulo M.P. [Department of Biological Sciences, Federal University of Piauí, Picos, Piauí (Brazil); Cavalcanti, Bruno C. [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil); Silva, Teresinha G.; Pitta, Marina G.R.; Lima, Maria do C.A. de; Galdino, Suely L.; Pitta, Ivan da R. [Department of Antibiotics, Federal, University of Pernambuco, Recife, Pernembuco (Brazil); Costa-Lotufo, Letícia V.; Moraes, Manoel O. [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil); Burbano, Rommel R. [Institute of Biological Sciences, Federal University of Pará, Belém, Pará (Brazil); Guecheva, Temenouga N.; Henriques, João A.P. [Biotechnology Center, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul (Brazil); Pessoa, Cláudia, E-mail: cpessoa@ufc.br [Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará (Brazil)

2013-04-01

Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione — AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione — AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl) -1,3-thiazolidine-2,4-dione — AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2, 4-dione — AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways. - Highlights: ► Thiazacridine derivatives induce mitochondrial-dependent apoptotic cell death. ► Thiazacridine derivatives inhibit DNA topoisomerase I action. ► Thiazacridine derivatives failed to cause genotoxicity on human lymphocytes.

Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives

International Nuclear Information System (INIS)

Barros, Francisco W.A.; Bezerra, Daniel P.; Ferreira, Paulo M.P.; Cavalcanti, Bruno C.; Silva, Teresinha G.; Pitta, Marina G.R.; Lima, Maria do C.A. de; Galdino, Suely L.; Pitta, Ivan da R.; Costa-Lotufo, Letícia V.; Moraes, Manoel O.; Burbano, Rommel R.; Guecheva, Temenouga N.; Henriques, João A.P.; Pessoa, Cláudia

2013-01-01

Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione — AC-4; (5ZE)-5-acridin-9-ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione — AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chloro-benzyl) -1,3-thiazolidine-2,4-dione — AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3-thiazolidine-2, 4-dione — AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also induced mitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways. - Highlights: ► Thiazacridine derivatives induce mitochondrial-dependent apoptotic cell death. ► Thiazacridine derivatives inhibit DNA topoisomerase I action. ► Thiazacridine derivatives failed to cause genotoxicity on human lymphocytes

Tropical Mangrove Mapping Using Fully-Polarimetric Radar Data

Directory of Open Access Journals (Sweden)

Bambang Trisasongko

2009-09-01

Full Text Available Although mangrove is one of important ecosystems in the world, it has been abused and exploited by human for various purposes. Monitoring mangrove is therefore required to maintain a balance between economy and conservation and provides up-to-date information for rehabilitation. Optical remote sensing data have delivered such information, however ever-changing atmospheric disturbance may significantly decrease thematic content. In this research, Synthetic Aperture Radar (SAR fully polarimetric data were evaluated to present an alternative for mangrove mapping. Assessment using three statistical trees was performed on both tonal and textural data. It was noticeable that textural data delivered fairly good improvement which reduced the error rate to around 5-6% at L-band. This suggests that insertion of textural data is more important than any information derived from decomposition algorithm.

A Multi-Functional Fully Distributed Control Framework for AC Microgrids

DEFF Research Database (Denmark)

Shafiee, Qobad; Nasirian, Vahidreza; Quintero, Juan Carlos Vasquez

2018-01-01

This paper proposes a fully distributed control methodology for secondary control of AC microgrids. The control framework includes three modules: voltage regulator, reactive power regulator, and active power/frequency regulator. The voltage regulator module maintains the average voltage of the mi......This paper proposes a fully distributed control methodology for secondary control of AC microgrids. The control framework includes three modules: voltage regulator, reactive power regulator, and active power/frequency regulator. The voltage regulator module maintains the average voltage...... of the microgrid distribution line at the rated value. The reactive power regulator compares the local normalized reactive power of an inverter with its neighbors’ powers on a communication graph and, accordingly, fine-tunes Q-V droop coefficients to mitigate any reactive power mismatch. Collectively, these two....../reactive power sharing. An AC microgrid is prototyped to experimentally validate the proposed control methodology against the load change, plug-and-play operation, and communication constraints such as delay, packet loss, and limited bandwidth....

Cell-free H-cluster synthesis and [FeFe] hydrogenase activation: all five CO and CN⁻ ligands derive from tyrosine.

Directory of Open Access Journals (Sweden)

Jon M Kuchenreuther

Full Text Available [FeFe] hydrogenases are promising catalysts for producing hydrogen as a sustainable fuel and chemical feedstock, and they also serve as paradigms for biomimetic hydrogen-evolving compounds. Hydrogen formation is catalyzed by the H-cluster, a unique iron-based cofactor requiring three carbon monoxide (CO and two cyanide (CN⁻ ligands as well as a dithiolate bridge. Three accessory proteins (HydE, HydF, and HydG are presumably responsible for assembling and installing the H-cluster, yet their precise roles and the biosynthetic pathway have yet to be fully defined. In this report, we describe effective cell-free methods for investigating H-cluster synthesis and [FeFe] hydrogenase activation. Combining isotopic labeling with FTIR spectroscopy, we conclusively show that each of the CO and CN⁻ ligands derive respectively from the carboxylate and amino substituents of tyrosine. Such in vitro systems with reconstituted pathways comprise a versatile approach for studying biosynthetic mechanisms, and this work marks a significant step towards an understanding of both the protein-protein interactions and complex reactions required for H-cluster assembly and hydrogenase maturation.

KOH activation of pitch-derived carbonaceous materials - Effect of carbonization degree

Energy Technology Data Exchange (ETDEWEB)

Krol, Magdalena [Institute of Open Cast Mining POLTEGOR-Institute, Parkowa, Wroclaw (Poland); Gryglewicz, Grazyna; Machnikowski, Jacek [Division of Polymer and Carbonaceous Materials, Faculty of Chemistry, Wroclaw University of Technology, Gdanska (Poland)

2011-01-15

Two series of mesophase pitches and semi-cokes of different carbonization degree were produced by heat treatment of anthracene oil derived pitches P1 and P4 in the temperature range of 460-700 C. These carbonaceous materials were activated with potassium hydroxide at 700 C using 1:3 reagents ratio to assess the effects of the precursor optical texture and carbonization degree on the activation behavior. The results show that the increase in the pitch pretreatment temperature suppresses propensity to the pore generation while enhancing particle breaking. The effect can be illustrated by decreases in the BET surface area S{sub BET} from {proportional_to} 2700 to {proportional_to} 1500 m{sup 2} g{sup -1} and the micropore volume V{sub DR} from {proportional_to} 0.85 to {proportional_to} 0.45 cm{sup 3} g{sup -1}. These parameters are inversely related with the H/C atomic ratio of precursor. In contrast, the anisotropic development of pitch coke, varying from flow type to mosaics, has a slight effect on the activation behaviour. The mechanism of porosity generation, that is proposed, stresses the role of hydrogen occurring at the edges of graphene layers and potassium metal insertion/deinsertion on the porosity development and particle disintegration during KOH activation of pitch-derived carbons. (author)

Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

Science.gov (United States)

Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

2017-08-01

Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of β-Dihydroagarofuran Derivatives.

Science.gov (United States)

Zhao, Ximei; Xi, Xin; Hu, Zhan; Wu, Wenjun; Zhang, Jiwen

2016-02-24

The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 β-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT-135°, IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 μg/g, respectively, which were much lower than that of celangulin-V (327.6 μg/g). These results illustrated that β-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development.

CNS active ergot alkaloid dihydro derivatives. Tritium labelling and characterization

International Nuclear Information System (INIS)

Egan, J.A.; Nugent, R.P.; Filer, C.N.

2016-01-01

The ergot alkaloids are an important class of medicinally useful substances and this report describes the high specific activity tritium labelling of two dihydro derivatives; namely, dihydroergotamine and dihydrobromocriptine. The former was prepared by the direct tritiation of ergotamine itself. However, efforts to perform an analogous direct tritiation on bromocriptine were unsuccessful and a multistep synthesis was required. (author)

MAGNETIC CYCLES IN A DYNAMO SIMULATION OF FULLY CONVECTIVE M-STAR PROXIMA CENTAURI

Energy Technology Data Exchange (ETDEWEB)

Yadav, Rakesh K.; Wolk, Scott J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Christensen, Ulrich R. [Max-Planck-Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Poppenhaeger, Katja, E-mail: rakesh.yadav@cfa.harvard.edu [Astrophysics Research Center, Queen’s University Belfast, Belfast BT7 1NN (United Kingdom)

2016-12-20

The recent discovery of an Earth-like exoplanet around Proxima Centauri has shined a spot light on slowly rotating fully convective M-stars. When such stars rotate rapidly (period ≲20 days), they are known to generate very high levels of activity that is powered by a magnetic field much stronger than the solar magnetic field. Recent theoretical efforts are beginning to understand the dynamo process that generates such strong magnetic fields. However, the observational and theoretical landscape remains relatively uncharted for fully convective M-stars that rotate slowly. Here, we present an anelastic dynamo simulation designed to mimic some of the physical characteristics of Proxima Centauri, a representative case for slowly rotating fully convective M-stars. The rotating convection spontaneously generates differential rotation in the convection zone that drives coherent magnetic cycles where the axisymmetric magnetic field repeatedly changes polarity at all latitudes as time progress. The typical length of the “activity” cycle in the simulation is about nine years, in good agreement with the recently proposed activity cycle length of about seven years for Proxima Centauri. Comparing our results with earlier work, we hypothesis that the dynamo mechanism undergoes a fundamental change in nature as fully convective stars spin down with age.

Hemin-Graphene Derivatives with Increased Peroxidase Activities Restrain Protein Tyrosine Nitration.

Science.gov (United States)

Xu, Huan; Yang, Zhen; Li, Hailing; Gao, Zhonghong

2017-12-14

Protein tyrosine nitration is implicated in the occurrence and progression of pathological conditions involving free radical reactions. It is well recognized that hemin can catalyze protein tyrosine nitration in the presence of nitrite and hydrogen peroxide. Generally, the catalytic efficiency is positively correlated to its peroxidase activity. In this study, however, it is found that the efficiency of hemin in catalyzing protein tyrosine nitration is largely suppressed after functionalization with graphene derivatives, even though its peroxidase-like activity is more than quadrupled. Further studies show that the oxidation of tyrosine is still observed for these composites; dityrosine formation, however, is greatly inhibited. Furthermore, these composites also exhibit strong effects on the oxidation of nitrite into nitrate. Therefore, we propose a mechanism in which hemin-graphene derivatives facilitate the oxidation of tyrosine and nitrite to produce tyrosyl radicals and nitrogen dioxide radicals in the presence of hydrogen peroxide, but graphene interlayers serve as barriers that hinder radical-radical coupling reactions; consequently, protein tyrosine nitration is restrained. This property of hemin-graphene derivatives, by which they catalyze substrate oxidation but suppress radical-radical coupling reactions, shows their great potential in selective oxidation procedures for byproduct removal. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.

Science.gov (United States)

Shiraki, Hiroaki; Kozar, Michael P; Melendez, Victor; Hudson, Thomas H; Ohrt, Colin; Magill, Alan J; Lin, Ai J

2011-01-13

In an attempt to separate the antimalarial activity of tafenoquine (3) from its hemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficiency patients, a series of 5-aryl-8-aminoquinoline derivatives was prepared and assessed for antimalarial activities. The new compounds were found metabolically stable in human and mouse microsomal preparations, with t(1/2) > 60 min, and were equal to or more potent than primaquine (2) and 3 against Plasmodium falciparum cell growth. The new agents were more active against the chloroquine (CQ) resistant clone than to the CQ-sensitive clone. Analogues with electron donating groups showed better activity than those with electron withdrawing substituents. Compounds 4bc, 4bd, and 4be showed comparable therapeutic index (TI) to that of 2 and 3, with TI ranging from 5 to 8 based on IC(50) data. The new compounds showed no significant causal prophylactic activity in mice infected with Plasmodium berghei sporozoites, but are substantially less toxic than 2 and 3 in mouse tests.

Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment.

OpenAIRE

Yamauchi, K; Tomita, M; Giehl, T J; Ellison, R T

1993-01-01

Although the antimicrobial activity of lactoferrin has been well described, its mechanism of action has been poorly characterized. Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin-derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 microM bovine lactoferrin and 20 microM lactoferricin rele...

Biological activity of some novel synthesized 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives: In vitro and in vivo antineoplastic activity

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Satyajit Dutta

2014-12-01

Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives and the basic compound 2-(4-methylphenylsulfonamidopentanedioic acid have been synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ovarian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female swiss albino mice against Ehrlich ascites carcinoma (EAC. Among the synthesized compounds, ureide, anilide, p-nitoanilide and o-bromoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid bis amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

Energy Technology Data Exchange (ETDEWEB)

Borgati, Thiago F.; Alves, Rosemeire B., E-mail: thfborgati@gmail.com, E-mail: rosebrondi@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Quimica; Teixeira, Robson R.; Freitas, Rossimiriam P. de; Perdigao, Thays G.; Silva, Silma F. da; Santos, Aline Aparecida dos [Universidade Federal de Vicosa, MG (Brazil). Departamento de Quimica; Bastidas, Alberto de Jesus O. [Laboratorio de Quimica Ecologica, Departamento de Quimica, Universidad de Los Andes, Nucleo Universitario Pedro Rincon Gutierrez, Merida (Viet Nam)

2013-06-15

Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10{sup -4} mol L{sup -1}. Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

Fully Depleted Charge-Coupled Devices

International Nuclear Information System (INIS)

Holland, Stephen E.

2006-01-01

We have developed fully depleted, back-illuminated CCDs that build upon earlier research and development efforts directed towards technology development of silicon-strip detectors used in high-energy-physics experiments. The CCDs are fabricated on the same type of high-resistivity, float-zone-refined silicon that is used for strip detectors. The use of high-resistivity substrates allows for thick depletion regions, on the order of 200-300 um, with corresponding high detection efficiency for near-infrared and soft x-ray photons. We compare the fully depleted CCD to the p-i-n diode upon which it is based, and describe the use of fully depleted CCDs in astronomical and x-ray imaging applications

Synthesis, antimalarial activity and molecular docking of hybrid 4-aminoquinoline-1,3,5-triazine derivatives.

Science.gov (United States)

Bhat, Hans Raj; Singh, Udaya Pratap; Thakur, Anjali; Kumar Ghosh, Surajit; Gogoi, Kabita; Prakash, Anil; Singh, Ramendra K

2015-10-01

A series of novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized in a five-steps reaction and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Entire synthetic derivatives showed higher antimalarial activity on the sensitive strain while two compounds, viz., 9a and 9c displayed good activity against both the strains of P. falciparum. The observed activity was further substantiated by docking study on both wild and qradruple mutant type P. falciparum dihydrofolate reductase-thymidylate synthase (pf-DHFR-TS). Copyright © 2015 Elsevier Inc. All rights reserved.

VISA Final Report: Fully Integrated Power Electronic Systems in Automotive Electronics

NARCIS (Netherlands)

Waffenschmidt, E.

2011-01-01

This report summarizes the activities related to the public funded project “Vollintegrierte leistungselektronische Systeme in der Automobilelektronik – VISA” (Fully Integrated Power Electronic Systems in Automotive Electronics). Aim of the project is to investigate the integration of components into

Urea derivatives on the move: cytokinin-like activity and adventitious rooting enhancement depend on chemical structure.

Science.gov (United States)

Ricci, A; Bertoletti, C

2009-05-01

Urea derivatives are synthetic compounds, some of which have proved to be positive regulators of cell division and differentiation. N-phenyl-N'-(2-chloro-4-pyridyl)urea (forchlorofenuron, CPPU) and N-phenyl-N'-(1,2,3-thiadiazol-5-yl)urea (thidiazuron, TDZ), well known urea cytokinin representatives, are extensively used in in vitro plant morphogenesis studies, as they show cytokinin-like activity often exceeding that of adenine compounds. In recent years, renewed interest in structure-activity relationship studies allowed identification of new urea cytokinins and other urea derivatives that specifically enhance adventitious root formation. In this review, we report the research history of urea derivatives, new insights into their biological activity, and recent progress on their mode of action.

Linear response approach to active Brownian particles in time-varying activity fields

Science.gov (United States)

Merlitz, Holger; Vuijk, Hidde D.; Brader, Joseph; Sharma, Abhinav; Sommer, Jens-Uwe

2018-05-01

In a theoretical and simulation study, active Brownian particles (ABPs) in three-dimensional bulk systems are exposed to time-varying sinusoidal activity waves that are running through the system. A linear response (Green-Kubo) formalism is applied to derive fully analytical expressions for the torque-free polarization profiles of non-interacting particles. The activity waves induce fluxes that strongly depend on the particle size and may be employed to de-mix mixtures of ABPs or to drive the particles into selected areas of the system. Three-dimensional Langevin dynamics simulations are carried out to verify the accuracy of the linear response formalism, which is shown to work best when the particles are small (i.e., highly Brownian) or operating at low activity levels.

Automatic Service Derivation from Business Process Model Repositories via Semantic Technology

NARCIS (Netherlands)

Leopold, H.; Pittke, F.; Mendling, J.

2015-01-01

Although several approaches for service identification have been defined in research and practice, there is a notable lack of fully automated techniques. In this paper, we address the problem of manual work in the context of service derivation and present an approach for automatically deriving

Linear Approach for Synchronous State Stability in Fully Connected PLL Networks

Directory of Open Access Journals (Sweden)

José R. C. Piqueira

2008-01-01

Full Text Available Synchronization is an essential feature for the use of digital systems in telecommunication networks, integrated circuits, and manufacturing automation. Formerly, master-slave (MS architectures, with precise master clock generators sending signals to phase-locked loops (PLLs working as slave oscillators, were considered the best solution. Nowadays, the development of wireless networks with dynamical connectivity and the increase of the size and the operation frequency of integrated circuits suggest that the distribution of clock signals could be more efficient if distributed solutions with fully connected oscillators are used. Here, fully connected networks with second-order PLLs as nodes are considered. In previous work, how the synchronous state frequency for this type of network depends on the node parameters and delays was studied and an expression for the long-term frequency was derived (Piqueira, 2006. Here, by taking the first term of the Taylor series expansion for the dynamical system description, it is shown that for a generic network with N nodes, the synchronous state is locally asymptotically stable.

A priori estimates and existence for a class of fully nonlinear elliptic equations in conformal geometry

OpenAIRE

Wang, Xu-Jia

2006-01-01

In this paper we prove the interior gradient and second derivative estimates for a class of fully nonlinear elliptic equations determined by symmetric functions of eigenvalues of the Ricci or Schouten tensors. As an application we prove the existence of solutions to the equations when the manifold is locally conformally flat or the Ricci curvature is positive.

Synthesis and characterization of dithiocarbamate chitosan derivatives with enhanced antifungal activity.

Science.gov (United States)

Qin, Yukun; Liu, Song; Xing, Ronge; Yu, Huahua; Li, Kecheng; Meng, Xiangtao; Li, Rongfeng; Li, Pengcheng

2012-06-20

In this study, ammonium dithiocarbamate chitosan (ADTCCS) and triethylene diamine dithiocarbamate chitosan (TEDADTCCS) derivatives were obtained respectively by mixing chitosan with carbon disulfide and ammonia (triethylenediamine). Their structures were confirmed by FT-IR, 1H NMR, XRD, DSC, SEM, and elemental analysis. Antifungal properties of them against the plant pathogenic fungi Fusarium oxysporum and Alternaria porri were investigated at concentrations ranged from 31.25 to 500 mg/L. The dithiocarbamate chitosan derivatives had enhanced antifungal activity compared with chitosan. Particularly, they showed obvious inhibitory effect on Fusarium oxysporum. At 500 mg/L, TEDADTCCS inhibited growth of F. oxysporum at 60.4%, stronger than polyoxin and triadimefon whose antifungal indexes were found to be 25.3% and 37.7%. The chitosan derivatives described here deserve further study for use in crop protection. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Soluble Epoxide Hydrolase Inhibitory Activity of Selaginellin Derivatives from Selaginella tamariscina

Directory of Open Access Journals (Sweden)

Jang Hoon Kim

2015-12-01

Full Text Available Selaginellin derivatives 1–3 isolated from Selaginella tamariscina were evaluated for their inhibition of soluble epoxide hydrolase (sEH to demonstrate their potential for the treatment of cardiovascular disease. All selaginellin derivatives (1–3 inhibited sEH enzymatic activity and PHOME hydrolysis, in a dose-dependent manner, with IC50 values of 3.1 ± 0.1, 8.2 ± 2.2, and 4.2 ± 0.2 μM, respectively. We further determined that the derivatives function as non-competitive inhibitors. Moreover, the predicted that binding sites and interaction between 1–3 and sEH were solved by docking simulations. According to quantitative analysis, 1–3 were confirmed to have high content in the roots of S. tamariscina; among them, selaginellin 3 exhibited the highest content of 189.3 ± 0.0 μg/g.

Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

Directory of Open Access Journals (Sweden)

Ümide Demir Özkay

2017-09-01

Full Text Available Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po, indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

Synthesis, antifungal activity, and QSAR studies of 1,6-dihydropyrimidine derivatives

Directory of Open Access Journals (Sweden)

Chirag Rami

2013-01-01

Full Text Available Introduction: A practical synthesis of pyrimidinone would be very helpful for chemists because pyrimidinone is found in many bioactive natural products and exhibits a wide range of biological properties. The biological significance of pyrimidine derivatives has led us to the synthesis of substituted pyrimidine. Materials and Methods: With the aim of developing potential antimicrobials, new series of 5-cyano-6-oxo-1,6-dihydro-pyrimidine derivatives namely 2-(5-cyano-6-oxo-4-substituted (aryl-1,6-dihydropyrimidin-2-ylthio-N-substituted (phenyl acetamide (C1-C41 were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR, mass analysis, and proton nuclear magnetic resonance ( 1 H NMR. All the compounds were screened for their antifungal activity against Candida albicans (MTCC, 227. Results and Discussion: Quantitative structure activity relationship (QSAR studies of a series of 1,6-dihydro-pyrimidine were carried out to study various structural requirements for fungal inhibition. Various lipophilic, electronic, geometric, and spatial descriptors were correlated with antifungal activity using genetic function approximation. Developed models were found predictive as indicated by their square of predictive regression values (r 2pred and their internal and external cross-validation. Study reveals that CHI_3_C, Molecular_SurfaceArea, and Jurs_DPSA_1 contributed significantly to the activity along with some electronic, geometric, and quantum mechanical descriptors. Conclusion: A careful analysis of the antifungal activity data of synthesized compounds revealed that electron withdrawing substitution on N-phenyl acetamide ring of 1,6-dihydropyrimidine moiety possess good activity.

One-pot synthesis and antiproliferative activity of novel double-modified derivatives of the polyether ionophore monensin A.

Science.gov (United States)

Klejborowska, Greta; Maj, Ewa; Wietrzyk, Joanna; Stefańska, Joanna; Huczyński, Adam

2018-05-02

Monensin A (MON) is a polyether ionophore antibiotic, which shows a wide spectrum of biological activity. New MON derivatives such as double-modified ester-carbonates and double-modified amide-carbonates were obtained by a new and efficient one-pot synthesis with triphosgene as the activating reagent and the respective alcohol or amine. All new derivatives were tested for their antiproliferative activity against two drug-sensitive (MES-SA, LoVo) and two drug-resistant (MES-SA/DX5, LoVo/DX) cancer cell lines, and were also studied for their antimicrobial activity against different Staphylococcus aureus and Staphylococcus epidermidis bacterial strains. For the first time, the activity of MON and its derivatives against MES-SA and MES-SA/DX5 were evaluated. © 2018 John Wiley & Sons A/S.

Synthesis of chitosan derivative with diethyldithiocarbamate and its antifungal activity.

Science.gov (United States)

Qin, Yukun; Xing, Ronge; Liu, Song; Li, Kecheng; Hu, Linfeng; Yu, Huahua; Chen, Xiaolin; Li, Pengcheng

2014-04-01

With an aim to discover novel chitosan derivatives with enhanced antifungal properties compared with chitosan. Diethyl dithiocarbamate chitosan (EtDTCCS) was investigated and its structure was well identified. The antifungal activity of EtDTCCS against Alternaria porri (A. porri), Gloeosporium theae sinensis Miyake (G. theae sinensis), and Stemphylium solani Weber (S. solani) was tested at 0.25, 0.5, and 1.0 mg/mL, respectively. Compared with plain chitosan, EtDTCCS shows better inhibitory effect with 93.2% inhibitory index on G. theae sinensis at 1.0 mg/mL, even stronger than for polyoxin (82.5%). It was inferred derivatives of this kind may find potential applications for the treatment of various crop-threatening diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

[Adsorption and desorption of dyes by waste-polymer-derived activated carbons].

Science.gov (United States)

Lian, Fei; Liu, Chang; Li, Guo-Guang; Liu, Yi-Fu; Li, Yong; Zhu, Ling-Yan

2012-01-01

Mesoporous activated carbons with high surface area were prepared from three waste polymers, i. e., tire rubber, polyvinyl chloride (PVC) and polyethyleneterephtalate (PET), by KOH activation. The adsorption/desorption characteristics of dyes (methylene blue and methyl orange) on the carbons were studied. The effects of pH, ionic strength and surface surfactants in the solution on the dye adsorption were also investigated. The results indicated that the carbons derived from PVC and PET exhibited high surface area of 2 666 and 2 831 m2 x g(-1). Their mesopore volume were as high as 1.06 and 1.30 cm3 g(-1), respectively. 98.5% and 97.0% of methylene blue and methyl orange were removed in 15 min by PVC carbon, and that of 99.5% and 95.0% for PET carbon. The Langmuir maximum adsorption capacity to these dyes was more than 2 mmol x g(-1), much higher than that of commercial activated carbon F400. Compared with Freundlich model, the adsorption data was fitted better by Langmiur model, indicating monolayer coverage on the carbons. The adsorption was highly dependent on solution pH, ionic strength and concentration of surface surfactants. The activated carbons exhibited higher adsorption to methylene blue than that of methyl orange, and it was very hard for both of the dyes to be desorbed. The observation in this study demonstrated that activated carbons derived from polymer waste could be effective adsorbents for the treatment of wastewater with dyes.

The fully Mobile City Government Project (MCity)

DEFF Research Database (Denmark)

Scholl, Hans; Fidel, Raya; Mai, Jens Erik

2006-01-01

The Fully Mobile City Government Project, also known as MCity, is an interdisciplinary research project on the premises, requirements, and effects of fully mobile, wirelessly connected applications (FWMC). The project will develop an analytical framework for interpreting the interaction and inter......The Fully Mobile City Government Project, also known as MCity, is an interdisciplinary research project on the premises, requirements, and effects of fully mobile, wirelessly connected applications (FWMC). The project will develop an analytical framework for interpreting the interaction...

Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

DEFF Research Database (Denmark)

Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

2014-01-01

Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

OpenAIRE

El Mokhtar Essassi; R. Bouhfid; Y. Kandri Rodi; S. Ferfra; H. Benzeid; Y. Ramli

2010-01-01

Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

Synthesis and Nrf2 Activating Ability of Thiourea and Vinyl Sulfoxide Derivatives

Energy Technology Data Exchange (ETDEWEB)

Shim, Young Sun; Hwang, Hyun Sook; Nam, Ghilsoo; Choi, Kyung Il [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2013-08-15

Thiourea and vinyl sulfoxide derivatives were designed based on the structures of sulforaphene and gallic acid, prepared and tested for HO-1 inducing activity as a measure of Nrf2 activation, and inhibitory effect on NO production as a measure of anti-inflammatory activity. Both series of compounds showed moderate activity on HO-1 induction, and no inhibitory effect on NO production. Interestingly the thiourea compound 6d showed better HO-1 induction (71% SFN) than the corresponding isothiocyanate compound 6a (55% SFN). Overall, it seemed that more efficient electrophile is needed to get more effective Nrf2 activator.

Electron-topological investigation of the structure-antitumor activity relationship of thiosemicarbazone derivatives.

Science.gov (United States)

Dimoglo, A S; Chumakov, Y M; Dobrova, B N; Saracoglu, M

1997-04-01

In the frameworks of the electron-topological method (ETM) the structure-antitumor activity relationship was investigated for a series of thiosemicarbazone derivatives. The series included 70 compounds. Conformational analysis and quantum-chemical calculations were carried out for each compound. The revealed activity feature showed a satisfactory description of the class of active compounds according to two different parameters P and alpha estimating the probabilities of the feature realization in the class of active compounds (they are equal to 0.94 and 0.86, correspondingly). The results of testing demonstrated the high ability of ETM in predicting the activity investigated.

New enamine derivatives of lapachol and biological activity

Directory of Open Access Journals (Sweden)

OLIVEIRA MAILCAR F.

2002-01-01

Full Text Available A convenient synthesis of the new enamine derivatives 2-(4-morpholinyl-3-(3-methyl-2-butenyl-1,4-naphthalenedione, 2-(1-piperidinyl-3-(3-methyl-2-butenyl-1,4-naphtalenedione and 2-(1-pyrrolidinyl-3-(3-methyl-2-butenyl-1,4-naphthalenedione was carried out from natural 2-hydroxy-3-(3-methyl-2-butenyl-1,4-naphthalenedione (lapachol and morpholine, piperidine and pyrrolidine. The structures of the products were established mainly by NMR analysis, including 2D experiments. Biological activities of these products were evaluated against Artemia salina, Aedes aegypti and cytotoxicity using A549 human breast cells.

Synthesis and characterization of chemically activated carbon derived from arecanut shell

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A. S. Jadhav

2016-03-01

Full Text Available Activated carbon (AC was prepared from areca-nut shell (AS by chemical activation using phosphoric acid (PA. Activated carbon was prepared in three batches using phosphoric acid of 50 gm, 100 gm, and 300 gm with varying impregnation ratios by weight of 1:1, 2:1 and 3:1, 4:1 each. Characterization of the prepared activated carbon was done by methylene blue number (MBN, iodine number (IN, acid adsorption test (AAT, and elemental composition. Activation was carried out at 400 C. It was found that activated carbon derived from areca-nut shell shown improved results for methylene blue number (MBN, iodine number (IN, and acid adsorption test(AAT. Thermal analysis was carried out to know the weight loss and SEM was performed to know the morphology of AC.

Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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Sophie R. Miller

2017-03-01

Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives

Directory of Open Access Journals (Sweden)

Sinara Mônica Vitalino de Almeida

2015-06-01

Full Text Available In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z-2-(acridin-9-ylmethylene-N-phenylhydrazinecarbothioamide derivatives (3a–h were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 104 to 1.0 × 106 M−1 and quenching constants from −0.2 × 104 to 2.18 × 104 M−1 indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z-2-(acridin-9-ylmethylene-N- (4-chlorophenyl hydrazinecarbothioamide (3f, while the most active compound in antiproliferative assay was (Z-2-(acridin-9-ylmethylene-N-phenylhydrazinecarbothioamide (3a. There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.

Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity.

Science.gov (United States)

Mohamad, Saharuddin Bin; Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Nakagawa, Yoshinori; Kawashima, Ken; Hori, Hitoshi

2003-01-01

Gc protein is the precursor for Gc protein-derived macrophage activating factor (GcMAF), with three phenotypes: Gc1f, Gc1s and Gc2, based on its electrophoretic mobility. The difference in electrophoretic mobility is because of the difference in its posttranslational sugar moiety composition. We compared the difference between Gc protein and GcMAF electrophoretic mobility using the isoelectric focusing (IEF) method. The tumoricidal activity of GcMAF-treated macrophage was evaluated after coculture with L-929 cell. The tumoricidal mechanism was investigated using TNF bioassay and nitric oxide (NO) release. The difference in Gc protein and GcMAF electrophoretic mobility was detected. The tumoricidal activity of GcMAF-treated macrophage was detected, but no release of TNF and NO was detected. The difference of isoelectric focusing mobility in Gc protein and GcMAF would be useful to develop a GcMAF detection method. GcMAF increased macrophage tumoricidal activity but TNF and NO release were not involved in the mechanism.

Collection/concentration of trace uranium for spectrophotometric detection using activated carbon and first-derivative spectrophotometry

International Nuclear Information System (INIS)

El-Sayed, A.A.; Hamed, M.M.; El-Reefy, S.; Hmmad, H.A.

2007-01-01

The need exists for preconcentration of trace and ultratrace amounts of uranium from environmental, geological and biological samples. The adsorption of uranium on various solids is important from the purification, environmental, and radioactivity waste disposal points of view. A method is described for the determination of traces of uranium using first-derivative spectrophotometry after adsorptive preconcentration of uranium on activated carbon. Various parameters that influence the adsorptive preconcentration of uranium on activated carbon, viz., pH, amounts of activated carbon and time of stirring and interference of metals have been studied. First-derivative spectrophotometry in conjunction with adsorptive preconcentration of uranium on activated carbon is used for determining uranium at concentration levels down to 20 ppb (w/v). (orig.)

Characterization and immunomodulatory activity of polysaccharides derived from Dendrobium tosaense.

Science.gov (United States)

Yang, Li-Chan; Lu, Ting-Jang; Hsieh, Chang-Chi; Lin, Wen-Chuan

2014-10-13

Dendrobium tosaense is a medicinal Dendrobium species widely used in traditional medicine. This study demonstrated some structural characterizations and immunomodulatory activity of the water-soluble polysaccharides derived from the stem of D. tosaense (DTP). DTP was fractioned using DEAE-650 M anion-exchange gel filtration chromatography, producing one neutral polysaccharide fraction (DTP-N), which was investigated for its structural characteristics, using HPAEC-PAD, HP-SEC, GC-MS, and NMR spectroscopy. DTP and DTP-N consisted of galactose, glucose, and mannose in ratios of 1:9.1:150.7 and 1:12.2:262.5, respectively. DTP-N comprised (1 → 4)Man as its main backbone, and its average molecular weight was 220 kDa. We also investigated the immunomodulatory effects of DTP administered orally to BALB/c mice for 3 weeks. DTP substantially boosted the population of splenic natural killer (NK) cells, NK cytotoxicity, macrophage phagocytosis, and cytokine induction in splenocytes. This is the first study to demonstrate the structural characteristics of an active polysaccharide derived from D. tosaense and its immunopharmacological effects in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of polyhexamethylene guanidine hydrochloride (PHMG) derivatives introduced into polylactide (PLA) on the activity of bacterial enzymes.

Science.gov (United States)

Walczak, Maciej; Richert, Agnieszka; Burkowska-But, Aleksandra

2014-11-01

The present study was aimed at investigating bactericidal properties of polylactide (PLA) films containing three different polyhexamethylene guanidine hydrochloride (PHMG) derivatives and effect of the derivatives on extracellular hydrolytic enzymes and intracellular dehydrogenases. All PHMG derivatives had a slightly stronger bactericidal effect on Staphylococcus aureus than on E. coli but only PHMG granular polyethylene wax (at the concentration of at least 0.6 %) has a bactericidal effect. PHMG derivatives introduced into PLA affected the activity of microbial hydrolases to a small extent. This means that the introduction of PHMG derivatives into PLA will not reduce its enzymatic biodegradation significantly. On the other hand, PHMG derivatives introduced into PLA strongly affected dehydrogenases activity in S. aureus than in E. coli.

Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

Science.gov (United States)

Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

2018-05-10

Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Comparative study on the antioxidant and anti-Toxoplasma activities of vanillin and its resorcinarene derivative.

Science.gov (United States)

Oliveira, Claudio B S; Meurer, Ywlliane S R; Oliveira, Marianne G; Medeiros, Wendy M T Q; Silva, Francisco O N; Brito, Ana C F; Pontes, Daniel de L; Andrade-Neto, Valter F

2014-05-07

A resorcinarene derivative of vanillin, resvan, was synthesized and characterized by spectroscopic techniques. We measured the cytotoxicity (in vivo and in vitro), antioxidant and anti-Toxoplasma activities of vanillin and the resorcinarene compound. Here we show that vanillin has a dose-dependent behavior with IC50 of 645 µg/mL through an in vitro cytotoxicity assay. However, we could not observe any cytotoxic response at higher concentrations of resvan (IC50 > 2,000 µg/mL). The in vivo acute toxicity assays of vanillin and resvan exhibited a significant safety margin indicated by a lack of systemic and behavioral toxicity up to 300 mg/kg during the first 30 min, 24 h or 14 days after administration. The obtained derivative showed greater antioxidative activity (84.9%) when comparing to vanillin (19.4%) at 1,000 μg/mL. In addition, vanillin presents anti-Toxoplasma activity, while resvan does not show that feature. Our findings suggest that this particular derivative has an efficient antioxidant activity and a negligible cytotoxic effect, making it a potential target for further biological investigations.

Design, synthesis of novel chitosan derivatives bearing quaternary phosphonium salts and evaluation of antifungal activity.

Science.gov (United States)

Tan, Wenqiang; Zhang, Jingjing; Luan, Fang; Wei, Lijie; Chen, Yuan; Dong, Fang; Li, Qing; Guo, Zhanyong

2017-09-01

Two novel chitosan derivatives modified with quaternary phosphonium salts were successfully synthesized, including tricyclohexylphosphonium acetyl chitosan chloride (TCPACSC) and triphenylphosphonium acetyl chitosan chloride (TPPACSC), and characterized by FTIR, 1 H NMR, and 13 C NMR spectra. The degree of substitution was also calculated by elemental analysis results. Their antifungal activities against Colletotrichum lagenarium, Watermelon fusarium, and Fusarium oxysporum were investigated in vitro using the radial growth assay, minimal inhibitory concentration, and minimum bactericidal concentration assay. The fungicidal assessment revealed that the synthesized chitosan derivatives had superior antifungal activity compared with chitosan. Especially, TPPACSC exhibited the best antifungal property with inhibitory indices of over 75% at 1.0mg/mL. The results obviously showed that quaternary phosphonium groups could effectively enhance antifungal activity of the synthesized chitosan derivatives. Meanwhile, it was also found that their antifungal activity was influenced by electron-withdrawing ability of the quaternary phosphonium salts. The synthetic strategy described here could be utilized for the development of chitosan as antifungal biomaterials. Copyright © 2017 Elsevier B.V. All rights reserved.

Albaconol, a Plant-Derived Small Molecule, Inhibits Macrophage Function by Suppressing NF-κB Activation and Enhancing SOCSI Expression

Institute of Scientific and Technical Information of China (English)

Qiuyan Liu; Xiaoli Shu; Li Wang; Anna Sun; Jikai Liu; Xuetao Cao

2008-01-01

Discovery and functional identification of plant-derived small compounds as the immunosuppressant attract much attention these years. Albaconol is a new kind of small compound, prenylated resorcinol, isolated from the fruiting bodies of the inedible mushroom Albatrellus confluens. Our previous studies showed that albaconol can inhibit tumor cell growth and dendritic cell maturation. However, the immunomodulatory roles and the underlying mechanisms of albaconol have not been fully understood. In this study we investigated the effects of aibaconol on the proliferation and LPS-induced proinflammatory cytokine production of macrophages. AIbaconol, when used at a dose higher than 1.0 μg/ml, inhibited proliferation of RAW264.7 cells in a dose- and time-dependent manner, and could induce cellular apoptosis when used at high dosage (≥7.5 μg/ml). Furthermore, we found that albaconol used at a lower dosage without apoptosis induction could significantly inhibit LPS-induced TNF-α, IL-6, IL-β and NO production in RAW264.7 cells. The inhibition of NF-κB activation and enhancement of SOCS1 expression in LPS-stimulated macrophages by albaconol may contribute to the above immunosuppressive or anti-inflammatory activities of aibaconoi. Our results suggest that albaconol may be a potential immunosuppressive and anti-inflammatory drug. Cellular & Molecular Immunology. 2008;5(4):271-278.

Synthesis and Antiplasmodial Activity of 2-(4-Methoxyphenyl-4-Phenyl-1,10-Phenanthroline Derivative Compounds

Directory of Open Access Journals (Sweden)

Nazudin

2012-08-01

Full Text Available A unique of synthetic methods was employed to prepare 2-(4-methoxyphenyl-4-phenyl-1,10-phenanthroline (5 derivatives from 4-methoxy-benzaldehyde (1, acetophenone (2, and 8-aminoquinoline (4 with aldol condensation and cyclization reactions. The derivatives were tested through antiplasmodial test. The synthesis of derivatives compound 5 was conducted in three steps. The 3-(4-methoxyphenyl-1-phenylpropenone 3 was synthesized through aldol condensation of 1 and 2 which has a yield of 96.42%. The compound 5 was synthesized through cyclization of compound 4 and 3 with 84.55% yield. The derivative of compound 5 was synthesized from compound 5 using DMS and DES reagents which refluxed for 21 and 22 h, to produce (1-N-methyl-9-(4-methoxyphenyl-7-phenyl-1,10-phenanthrolinium sulfate (6 and (1-N-ethyl-9-(4-methoxyphenyl-7-phenyl-1,10-phenanthrolinium sulfate (7 with 91.42 and 86.36% yields, respectively. Results of in vitro testing of antiplasmodial activity of compound 5 derivatives (i.e., compound 6 and 7 against chloroquine-resistant P. falciparum FCR3 strain showed that compound 7 had higher antimalarial activity than compounds 5 and 6. Whereas, results of in vitro testing against chloroquine-sensitive P. falciparum D10 strain showed that compound 6 has higher antimalarial activity than compounds 5 and 7.

New Potentially Active Pyrazinamide Derivatives Synthesized Under Microwave Conditions

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Ondrej Jandourek

2014-07-01

Full Text Available A series of 18 N-alkyl substituted 3-aminopyrazine-2-carboxamides was prepared in this work according to previously experimentally set and proven conditions using microwave assisted synthesis methodology. This approach for the aminodehalogenation reaction was chosen due to higher yields and shorter reaction times compared to organic reactions with conventional heating. Antimycobacterial, antibacterial, antifungal and photosynthetic electron transport (PET inhibiting in vitro activities of these compounds were investigated. Experiments for the determination of lipophilicity were also performed. Only a small number of substances with alicyclic side chain showed activity against fungi which was the same or higher than standards and the biological efficacy of the compounds increased with rising lipophilicity. Nine pyrazinamide derivatives also inhibited PET in spinach chloroplasts and the IC50 values of these compounds varied in the range from 14.3 to 1590.0 μmol/L. The inhibitory activity was connected not only with the lipophilicity, but also with the presence of secondary amine fragment bounded to the pyrazine ring. Structure-activity relationships are discussed as well.

Derivation of the Hall and extended magnetohydrodynamics brackets

Energy Technology Data Exchange (ETDEWEB)

D' Avignon, Eric C., E-mail: cavell@physics.utexas.edu; Morrison, Philip J., E-mail: morrison@physics.utexas.edu [Department of Physics and Institute for Fusion Studies, The University of Texas at Austin, Austin, Texas 78712 (United States); Lingam, Manasvi, E-mail: mlingam@princeton.edu [Department of Astrophysical Sciences, Princeton University, Princeton, New Jersey 08544 (United States)

2016-06-15

There are several plasma models intermediate in complexity between ideal magnetohydrodynamics (MHD) and two-fluid theory, with Hall and Extended MHD being two important examples. In this paper, we investigate several aspects of these theories, with the ultimate goal of deriving the noncanonical Poisson brackets used in their Hamiltonian formulations. We present fully Lagrangian actions for each, as opposed to the fully Eulerian, or mixed Eulerian-Lagrangian, actions that have appeared previously. As an important step in this process, we exhibit each theory's two advected fluxes (in analogy to ideal MHD's advected magnetic flux), discovering also that with the correct choice of gauge they have corresponding Lie-dragged potentials resembling the electromagnetic vector potential, and associated conserved helicities. Finally, using the Euler-Lagrange map, we show how to derive the noncanonical Eulerian brackets from canonical Lagrangian ones.

SYNTHESIS, REACTIVITY AND BIOLOGICAL ACTIVITY OF QUINOXALIN-2-ONE DERIVATIVES

Directory of Open Access Journals (Sweden)

El Mokhtar Essassi

2010-04-01

Full Text Available Quinoxalines have a great interest in various fields and particularly in chemistry, biology and pharmacology. It enabled the researchers to develop many methods for their preparations and to seek new fields of application. In this review, we’ll expose different methods of synthesis of the quinoxalin-2-one, its reactivity and finally we’ll discuss the various biological activities of its derivatives.

Synthesis and Structure-Activity Relationships of a Series of Aporphine Derivatives with Antiarrhythmic Activities and Acute Toxicity

Directory of Open Access Journals (Sweden)

Hui Wang

2016-11-01

Full Text Available Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF, induced by CHCl3, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl2. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d, three bromo-substituted products of crebanine (2a, 2b, 2c, N-methylcrebanine (2d, and dehydrostephanine (4a displayed antiarrhythmic effects in the CHCl3-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl3 (p < 0.05, increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl2 (p < 0.01, and the number of rats that maintained sinus rhythm for more than 20 min (p < 0.01. Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD50 = 59.62 mg/kg, mice, simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.

Water-soluble derivatives of 25-OCH3-PPD and their anti-proliferative activities.

Science.gov (United States)

Zhou, Wu-Xi; Sun, Yuan-Yuan; Yuan, Wei-Hui; Zhao, Yu-Qing

2017-05-01

(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH 3 -PPD, AD-1) is a dammarane-type sapogenin showing anti-tumor potential. In the search for new anti-tumor agents with higher potency than our previously identified compound 25-OCH 3 -PPD, 11 novel sulfamic acid and diacid derivatives that could improve water solubility and contribute to good drug potency and pharmacokinetic profiles were designed and synthesized. Their in vitro anti-tumor activities in MCF-7, A-549, HCT-116, and BGC-823 cell lines and one normal cell line were tested by standard MTT assay. Results showed that compared with compound 25-OCH 3 -PPD, compounds 1, 4, and 5 exhibited higher cytotoxic activity on almost all cell lines, together with lower toxicity in the normal cell. In particular, compound 1 exhibited the best anti-tumor activity in the in vitro assays. The water solubility of 25-OCH 3 -PPD and its derivatives was tested and the results showed that the solubility of 25-OCH 3 -PPD sulfamic acid and diacid derivatives were better than that of 25-OCH 3 -PPD in water, which may provide valuable data for the research and development of new anti-tumor agents. Copyright © 2017 Elsevier Inc. All rights reserved.

The 5D Fully-Covariant Theory of Gravitation and Its Astrophysical Applications

Directory of Open Access Journals (Sweden)

Tianxi Zhang

2014-12-01

Full Text Available In this paper, we comprehensively review the five-dimensional (5D fully-covariant theory of gravitation developed by Zhang two decades ago and its recent applications in astrophysics and cosmology. This 5D gravity describes not only the fields, but also the matter and its motion in a 5D spacetime. The greatest advantage of this theory is that there does not exist any unknown parameter, so that we can apply it to explain astrophysical and cosmological issues by quantitatively comparing the results obtained from it with observations and to predict new effects that could not be derived from any other gravitational theories. First, the 5D covariant description of matter and its motion enabled Zhang to analytically derive the fifteenth component of the 5D energy-momentum tensor of matter ( T - 44 , which significantly distinguishes this 5D gravity from other 5D gravitational theories that usually assumed a T - 44 with an unknown parameter, called the scalar charge s, and, thus, to split the 5D covariant field equation into (4 + 1 splitting form as the gravitational, electromagnetic, and scalar field equations. The gravitational field equation turns into the 4D Einstein’s field equation of general relativity if the scalar field is equal to unity. Then, Zhang solved the field equations and obtained an exact static spherically-symmetric external solution of the gravitational, electromagnetic and scalar fields, in which all integral constants were completely determined with a perfect set of simple numbers and parameters that only depend on the mass and electric charge of the matter, by comparing with the obtained weak internal solution of the fields at a large radial distance. In the Einstein frame, the exact field solution obtained from the 5D fully-covariant theory of gravitation reduces to the Schwarzschild solution when the matter is electrically neutral and the fields are weak in strength. This guarantees that the four fundamental tests (light

Synthesis and Antiproliferative Activity of Some Novel Triazole Derivatives from Dehydroabietic Acid

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Mariano Walter Pertino

2014-02-01

Full Text Available Dehydroabietic acid (DHA is a naturally occurring diterpene with different and relevant biological activities. Previous studies have shown that some DHA derivatives display antiproliferative activity. However, the reported compounds did not include triazole derivatives. Starting from DHA (8,11,13-abietatrien-18-oic acid, and its alcohol dehydroabietinol (8,11,13-abietatrien-18-ol, four alkyl esters were prepared. The alkyl terpenes were treated with different aromatic azides to synthesize hybrid compounds using click chemistry. Some 16 new DHA hybrids were thus synthesized and their structures were confirmed by spectroscopic and spectrometric means. The antiproliferative activity of the new compounds was assessed towards human cell lines, namely normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, lung cancer (SK-MES-1 and bladder carcinoma (J82 cells. Better antiproliferative effect was found for compound 5, with an IC50 of 6.1 μM and selectivity on SK-MES-1 cells. Under the same experimental conditions, the IC50 of etoposide, was 1.83 µM.

Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives.

Science.gov (United States)

Pereira, Glaécia A N; Souza, Gisele C; Santos, Lourivaldo S; Barata, Lauro E S; Meneses, Carla C F; Krettli, Antoniana U; Daniel-Ribeiro, Cláudio Tadeu; Alves, Cláudio Nahum

2017-09-01

The absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventional antimalarial drugs result in a worrisome scenario making the search for new drugs a priority. In the present study, the activities of nine neolignan derivatives were evaluated as follows: (i) against blood forms of chloroquine-resistant Plasmodium falciparum (clone W2), using the tritiated hypoxanthine incorporation and anti-HRPII assays; (ii) for cytotoxic activity against cultured human hepatoma cells (HepG2); and (iii) for intermolecular interaction with the P. falciparum cysteine protease of falcipain-2 (F2) by molecular docking. The neolignan derivatives 9 and 10 showed activity against the blood form of the chloroquine-resistant P. falciparum clone W2 and were not cytotoxic against cultured human hepatoma cells. A molecular docking study of these two neolignans with FP2 revealed several intermolecular interactions that should guide the design of future analogs. © 2017 John Wiley & Sons A/S.

Sharing Malaysian experience with the development of biotechnology-derived food crops.

Science.gov (United States)

Abu Bakar, Umi K; Pillai, Vilasini; Hashim, Marzukhi; Daud, Hassan Mat

2005-12-01

Biotechnology-derived food crops are currently being developed in Malaysia mainly for disease resistance and improved post harvest quality. The modern biotechnology approach is adopted because of its potential to overcome constraints faced by conventional breeding techniques. Research on the development of biotechnology-derived papaya, pineapple, chili, passion fruit, and citrus is currently under way. Biotechnology-derived papaya developed for resistance to papaya ringspot virus (PRSV) and improved postharvest qualities is at the field evaluation stage. Pineapple developed for resistance to fruit black heart disorder is also being evaluated for proof-of-concept. Other biotechnology-derived food crops are at early stages of gene cloning and transformation. Activities and products involving biotechnology-derived crops will be fully regulated in the near future under the Malaysian Biosafety Law. At present they are governed only by guidelines formulated by the Genetic Modification Advisory Committee (GMAC), Malaysia. Commercialization of biotechnology-derived crops involves steps that require GMAC approval for all field evaluations and food-safety assessments before the products are placed on the market. Public acceptance of the biotechnology product is another important factor for successful commercialization. Understanding of biotechnology is generally low among Malaysians, which may lead to low acceptance of biotechnology-derived products. Initiatives are being taken by local organizations to improve public awareness and acceptance of biotechnology. Future research on plant biotechnology will focus on the development of nutritionally enhanced biotechnology-derived food crops that can provide more benefits to consumers.

Carpatizine, a novel bridged oxazine derivative generated by non-enzymatic reactions.

Science.gov (United States)

Fu, Peng; MacMillan, John B

2017-06-27

Carpatizine (1), a new bridged oxazine derivative, was isolated from a marine-derived Streptomyces strain SNE-011. The structure was fully determined by spectroscopic analysis, ECD calculations and chemical methods. A plausible non-enzymatic reaction mechanism from daryamide D leading to carpatizine was presented, which was confirmed by chemical transformation.

Cytotoxicity and Radiosensitising Activity of Synthesized Dinitrophenyl Derivatives of 5-Fluorouracil

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Khosrou Abdi

2012-07-01

Full Text Available Background and the purpose of the study: Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In thepresent investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide,and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions wasinvestigated.Methods: 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substitutedbenzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking,group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively.Results and major conclusion: Findings of the present study showed that

Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D derivatives.

Science.gov (United States)

Chen, Zhong; Duan, Huaqing; Wang, Minglei; Han, Li; Liu, Yanli; Zhu, Yongming; Yang, Shilin

2015-06-15

The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated. Structure-activity relationship and structure-toxicity relationship had been observed. The mice acute toxicity of compound 11 was reduced greatly than that of PSA. This study indicates that compound 11 may represent an interesting class of potent antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The present study has important significance for the development of antitumor saponins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis, characterization, X-ray crystallography, acetyl cholinesterase inhibition and antioxidant activities of some novel ketone derivatives of gallic hydrazide-derived Schiff bases.

Science.gov (United States)

Gwaram, Nura Suleiman; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Buckle, Michael J C; Sukumaran, Sri Devi; Chung, Lip Yong; Othman, Rozana; Alhadi, Abeer A; Yehye, Wageeh A; Hadi, A Hamid A; Hassandarvish, Pouya; Khaledi, Hamid; Abdelwahab, Siddig Ibrahim

2012-02-28

Alzheimer's disease (AD) is the most common form of dementia among older people and the pathogenesis of this disease is associated with oxidative stress. Acetylcholinesterase inhibitors with antioxidant activities are considered potential treatments for AD. Some novel ketone derivatives of gallic hydrazide-derived Schiff bases were synthesized and examined for their antioxidant activities and in vitro and in silico acetyl cholinesterase inhibition. The compounds were characterized using spectroscopy and X-ray crystallography. The ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays revealed that all the compounds have strong antioxidant activities. N-(1-(5-bromo-2-hydroxyphenyl)-ethylidene)-3,4,5-trihydroxybenzohydrazide (2) was the most potent inhibitor of human acetyl cholinesterase, giving an inhibition rate of 77% at 100 μM. Molecular docking simulation of the ligand-enzyme complex suggested that the ligand may be positioned in the enzyme's active-site gorge, interacting with residues in the peripheral anionic subsite (PAS) and acyl binding pocket (ABP). The current work warrants further preclinical studies to assess the potential for these novel compounds for the treatment of AD.

Design, Synthesis, and Antibacterial Activities of Novel Heterocyclic Arylsulphonamide Derivatives.

Science.gov (United States)

Singh, Anuradha; Srivastava, Ritika; Singh, Ramendra K

2017-02-13

Design, synthesis, and antibacterial activities of a series of arylsulphonamide derivatives as probable peptide deformylase (PDF) inhibitors have been discussed. Compounds have been designed following Lipinski's rule and after docking into the active site of PDF protein (PDB code: 1G2A) synthesized later on. Furthermore, to assess their antibacterial activity, screening of the compound was done in vitro conditions against Gram-positive and Gram-negative bacterial strains. In silico, studies revealed these compounds as potential antibacterial agents and this fact was also supported by their prominent scoring functions. Antibacterial results indicated that these molecules possessed a significant activity against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli with MIC values ranging from 0.06 to 0.29 μM. TOPKAT results showed that high LD 50 values and the compounds were assumed non-carcinogenic when various animal models were studied computationally.

Derivation of Huntington Disease affected Genea046 human embryonic stem cell line

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Biljana Dumevska

2016-03-01

Full Text Available The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1–60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.

Manipulation of Thermally Activated Delayed Fluorescence of Blue Exciplex Emission: Fully Utilizing Exciton Energy for Highly Efficient Organic Light Emitting Diodes with Low Roll-Off.

Science.gov (United States)

Wang, Zixing; Wang, Hedan; Zhu, Jun; Wu, Peng; Shen, Bowen; Dou, Dehai; Wei, Bin

2017-06-28

The application of exciplex energy has become a unique way to achieve organic light-emitting diodes (OLEDs) with high efficiencies, low turn-on voltage, and low roll-off. Novel δ-carboline derivatives with high triplet energy (T 1 ≈ 2.92 eV) and high glass transition temperature (T g ≈ 153 °C) were employed to manipulate exciplex emissions in this paper. Deep blue (peak at 436 nm) and pure blue (peak at 468 nm) thermally activated delayed fluorescence (TADF) of exciplex OLEDs were demonstrated by utilizing them as emitters with the maximum current efficiency (CE) of 4.64 cd A -1 , power efficiency (PE) of 2.91 lm W -1 , and external quantum efficiency (EQE) of 2.36%. Highly efficient blue phosphorescent OLEDs doped with FIrpic showed a maximum CE of 55.6 cd A -1 , PE of 52.9 lm W -1 , and EQE of 24.6% respectively with very low turn on voltage at 2.7 V. The devices still remain high CE of 46.5 cd A -1 at 100 cd m -2 , 45.4 cd A -1 at 1000 cd m -2 and 42.3 cd A -1 at 5000 cd m -2 with EQE close to 20% indicating low roll-off. Manipulating blue exciplex emissions by chemical structure gives an ideal strategy to fully utilize all exciton energies for lighting of OLEDs.

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain.

Science.gov (United States)

Lim, Eun Yeong; Kim, Yun Tai

2016-01-01

Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and allodynia. The number of patients with this type of pain has increased rapidly in recent years. Yet, available neuropathic pain medicines have undesired side effects, such as tolerance and physical dependence, and do not fully alleviate the pain. The mechanisms of neuropathic pain are still not fully understood. Injury causes inflammation and immune responses and changed expression and activity of receptors and ion channels in peripheral nerve terminals. Additionally, neuroinflammation is a known factor in the development and maintenance of neuropathic pain. During neuropathic pain development, the C-C motif chemokine receptor 2 (CCR2) acts as an important signaling mediator. Traditional plant treatments have been used throughout the world for treating diseases. We and others have identified food-derived compounds that alleviate neuropathic pain. Here, we review the natural compounds for neuropathic pain relief, their mechanisms of action, and the potential benefits of natural compounds with antagonistic effects on GPCRs, especially those containing CCR2, for neuropathic pain treatment.

Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity

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Qing Li

2018-03-01

Full Text Available Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating “click reaction” with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC50 < 0.01 mg mL−1 was more efficient than that of derivatives with triazole and Vitamin C. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH and hydroxyl radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

Production of active pigment epithelium-derived factor inE. coli.

Science.gov (United States)

Zhang, Tao; Guan, Ming; Lu, Yuan

2005-03-01

Human pigment epithelium-derived factor (PEDF), a neurotrophic factor, is the most potent natural inhibitor of angiogenesis. To produce the active PEDF, the gene coding for the human PEDF protein was expressed in E. coli. The rPEDF protein was expressed at 457 mg l-1 as a soluble protein. The yield of purified GST fusion protein was 14 mg l-1. Purified rPEDF inhibited tube formation in endothelial cells.

Fully automated data acquisition, processing, and display in equilibrium radioventriculography

International Nuclear Information System (INIS)

Bourguignon, M.H.; Douglass, K.H.; Links, J.M.; Wagner, H.N. Jr.; Johns Hopkins Medical Institutions, Baltimore, MD

1981-01-01

A fully automated data acquisition, processing, and display procedure was developed for equilibrium radioventriculography. After a standardized acquisition, the study is automatically analyzed to yield both right and left ventricular time-activity curves. The program first creates a series of edge-enhanced images (difference between squared images and scaled original images). A marker point within each ventricle is then identified as that pixel with maximum counts to the patient's right and left of the count center of gravity of a stroke volume image. Regions of interest are selected on each frame as the first contour of local maxima of the two-dimensional second derivative (pseudo-Laplacian) which encloses the appropriate marker point, using a method developed by Goris. After shifting the left ventricular end-systolic region of interest four pixels to the patient's left, a background region of interest is generated as the crescent-shaped area of the shifted region of interest not intersected by the end systolic region. The average counts/pixel in this background region in the end systolic frame of the original study are subtracted from each pixel in all frames of the gated study. Right and left ventricular time-activity curves are then obtained by applying each region of interest to its corresponding background-subtracted frame, and the ejection fraction, end diastolic, end systolic, and stroke counts determined for both ventricles. In fourteen consecutive patients, in addition to the automatic ejection fractions, manually drawn regions of interest were used to obtain ejection fractions for both ventricles. The manual regions of interest were drawn twice, and the average obtained. (orig./TR)

Progress report on a fully automatic Gas Tungsten Arc Welding (GTAW) system development

Energy Technology Data Exchange (ETDEWEB)

Daumeyer, G.J. III

1994-12-01

A plan to develop a fully automatic gas tungsten arc welding (GTAW) system that will utilize a vision-sensing computer (which will provide in-process feedback control) is presently in work. Evaluations of different technological aspects and system design requirements continue. This report summaries major activities in the plan`s successful progress. The technological feasibility of producing the fully automated GTAW system has been proven. The goal of this process development project is to provide a production-ready system within the shortest reasonable time frame.

Amino acid linked bromobenzoyl thiourea derivatives: syntheses, characterization and antimicrobial activities

International Nuclear Information System (INIS)

Raheel, A.; Din, I.U.; Badshah, A.; Rauf, M.K.; Andleeb, S.

2016-01-01

Five new bromobenzoyl thiourea derivatives (1-5) linked with different amino acids were synthesized via the reaction of bromobenzoyl chloride with potassium thiocyanide and the corresponding amines. The synthetic compounds were characterized by single crystal XRD, IR and NMR (/sup 1/H- and /sup 13/C-) spectroscopy in addition to elemental analysis and melting point determinations. These compounds were also preliminary analyzed for antifungal and antibacterial activity against different strains of fungi and bacteria, respectively. The data suggest that the compounds exhibited promising antimicrobial activity and may prove potential lead compounds as antimicrobial agent. (author)

Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

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Julia K Bialek

Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

Bioengineered nisin A derivatives with enhanced activity against both Gram positive and Gram negative pathogens.

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Des Field

Full Text Available Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G, with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.

Bioengineered Nisin A Derivatives with Enhanced Activity against Both Gram Positive and Gram Negative Pathogens

Science.gov (United States)

Field, Des; Begley, Maire; O’Connor, Paula M.; Daly, Karen M.; Hugenholtz, Floor; Cotter, Paul D.; Hill, Colin; Ross, R. Paul

2012-01-01

Nisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria. PMID:23056510

Antioxidant and cytotoxic activity of mono- and bissalicylic acid derivatives

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Đurendić Evgenija A.

2014-01-01

Full Text Available A simple synthesis of mono- and bis-salicylic acid derivatives 1-10 by the transesterification of methyl salicylate (methyl 2-hydroxybenzoate with 3-oxapentane-1,5-diol, 3,6- dioxaoctane-1,8-diol, 3,6,9-trioxaundecane-1,11-diol, propane-1,2-diol or 1-aminopropan- 2-ol in alkaline conditions is reported. All compounds were tested in vitro on three malignant cell lines (MCF-7, MDA-MB-231, PC-3 and one non-tumor cell line (MRC- 5. Strong cytotoxicity against prostate PC-3 cancer cells expressed compounds 3, 4, 6, 9 and 10, all with the IC50 less than 10 μmol/L, which were 11-27 times higher than the cytotoxicity of antitumor drug doxorubicin. All tested compounds were not toxic against the non-tumor MRC-5 cell line. Antioxidant activity of the synthesized derivatives was also evaluated. Compounds 2, 5 and 8 were better OH radical scavengers than commercial antioxidants BHT and BHA. The synthesized compounds showed satisfactory scavenger activity, which was studied by QSAR modeling. A good correlation between the experimental variables IC50 DPPH and IC50 OH and MTI (molecular topological indices molecular descriptors and CAA (accessible Connolly solvent surface area for the new compounds 1, 3, and 5 was observed.

In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives

Science.gov (United States)

Rocha e Silva, Luiz Francisco; Nogueira, Karla Lagos; Pinto, Ana Cristina da Silva; Katzin, Alejandro Miguel; Sussmann, Rodrigo A. C.; Muniz, Magno Perêa; Neto, Valter Ferreira de Andrade; Chaves, Francisco Célio Maia; Coutinho, Julia Penna; Lima, Emerson Silva; Krettli, Antoniana Ursine; Tadei, Wanderli Pedro

2015-01-01

4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots. O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivo antimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitro protein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivo result for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential. PMID:25801563

The effects of platelet lysate patches on the activity of tendon-derived cells.

Science.gov (United States)

Costa-Almeida, Raquel; Franco, Albina R; Pesqueira, Tamagno; Oliveira, Mariana B; Babo, Pedro S; Leonor, Isabel B; Mano, João F; Reis, Rui L; Gomes, Manuela E

2018-03-01

Platelet-derived biomaterials are widely explored as cost-effective sources of therapeutic factors, holding a strong potential for endogenous regenerative medicine. Particularly for tendon repair, treatment approaches that shift the injury environment are explored to accelerate tendon regeneration. Herein, genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of human-derived therapeutic factors in patch augmentation strategies aiming at tendon repair. Developed PL patches exhibited a controlled release profile of PL proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an antibacterial effect by preventing the adhesion, proliferation and biofilm formation by S. aureus, a common pathogen in orthopaedic surgical site infections. Furthermore, these patches supported the activity of human tendon-derived cells (hTDCs). Cells were able to proliferate over time and an up-regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon-related extracellular matrix proteins, namely collagen type I and tenascin C. In summary, PL patches can act as a reservoir of biomolecules derived from PL and support the activity of native tendon cells, being proposed as bioinstructive patches for tendon regeneration. Platelet-derived biomaterials hold great interest for the delivery of therapeutic factors for applications in endogenous regenerative medicine. In the particular case of tendon repair, patch augmentation strategies aiming at shifting the injury environment are explored to improve tendon regeneration. In this study, PL patches were developed with remarkable features, including the controlled release of growth factors and antibacterial efficacy. Remarkably, PL patches supported the activity of native tendon cells by up-regulating tenogenic genes and enabling the deposition of ECM proteins. This patch holds great potential towards

Docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.

Science.gov (United States)

Vijayaraghavan, Shilpa; Mahajan, Supriya

2017-04-15

A series of 4-anilinoquinoline triazine derivatives were designed, synthesized and screened for in vivo antimalarial activity against a chloroquine-sensitive strain of Plasmodium berghei. The compounds were further subjected to in vitro antimalarial activity against chloroquine-resistant W2 strain of Plasmodium falciparum and β-haematin inhibition studies. All the compounds exhibited in vivo antimalarial activity better than that shown by the standard drug, chloroquine. Twelve out of fifteen compounds showed better inhibition than that of chloroquine against chloroquine-resistant W2 strain of Plasmodium falciparum. Ten compounds showed β-haematin inhibition, better than that of chloroquine, with IC 50 values in the range of 18-25µM. One compound, 3k, was found to be better than artemisinin against W2 strain of Plasmodium falciparum and also displayed the best β-haematin inhibitory activity, thereby becoming eligible to be explored as a potential lead for antimalarial chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fully implicit, coupled procedures in computational fluid dynamics an engineer's resource book

CERN Document Server

Mazhar, Zeka

2016-01-01

This book introduces a new generation of superfast algorithms for the treatment of the notoriously difficult velocity-pressure coupling problem in incompressible fluid flow solutions. It provides all the necessary details for the understanding and implementation of the procedures. The derivation and construction of the fully-implicit, block-coupled, incomplete decomposition mechanism are given in a systematic, but easy fashion. Worked-out solutions are included, with comparisons and discussions. A complete program code is included for faster implementation of the algorithm. A brief literature review of the development of the classical solution procedures is included as well. .

Antitumor and Antimicrobial Activity of Some Cyclic Tetrapeptides and Tripeptides Derived from Marine Bacteria

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Subrata Chakraborty

2015-05-01

Full Text Available Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu. Cyclic tetrapeptides (CtetPs were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP scaffold, cyclo(Gly-l-Ser-l-Pro, cyclo(Ser-l-Pro-l-Glu and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.

Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity

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Krzysztof M. Borys

2012-02-01

Full Text Available A halogenmethylsulfonyl moiety is incorporated in numerous active herbicides and fungicides. The synthesis of tribromomethyl phenyl sulfone derivatives as novel potential pesticides is reported. The title sulfone was obtained by following three different synthetic routes, starting from 4-chlorothiophenol or 4-halogenphenyl methyl sulfone. Products of its subsequent nitration were subjected to the SNAr reactions with ammonia, amines, hydrazines and phenolates to give 2-nitroaniline, 2-nitrophenylhydrazine and diphenyl ether derivatives. Reduction of the nitro group of 4-tribromomethylsulfonyl-2-nitroaniline yielded the corresponding o-phenylenediamine substrate for preparation of structurally varied benzimidazoles.

Assay of flippase activity in proteoliposomes using fluorescent lipid derivatives

DEFF Research Database (Denmark)

Marek, Magdalena; Günther-Pomorski, Thomas

2016-01-01

Specific membrane proteins, termed lipid flippases, play a central role in facilitating the movement of lipids across cellular membranes. In this protocol, we describe the reconstitution of ATP-driven lipid flippases in liposomes and the analysis of their in vitro flippase activity based on the use...... of fluorescent lipid derivatives. Working with purified and reconstituted systems provides a well-defined experimental setup and allows to directly characterize these membrane proteins at the molecular level....

Synthesis and Spectroscopic Characterization of Some New Biological Active Azo–Pyrazoline Derivatives

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Farouq E. Hawaiz

2012-01-01

Full Text Available A number of 3-[4-(benzyloxy-3-(2-Chlorophenylazo-phenyl]-5-(substituted-phenyl-1-substituted-2-pyrazolines( 4a-j and (5a-j have been synthesized by diazotization of 2-chloroaniline and its coupling reaction with 4-hydroxy acetophenone, followed by benzyloxation of the hydroxyl group to give the substrate [4-benzyloxy-3-(2-chlorophenylazo-acetophenone (1].The prepared starting material (1 has been reacted with different substituted benzaldehydes to give a new series of chalcone derivatives 1-[(4-benzyloxy-3-(2-chloro-phenylazo-phenyl]-3-(substituted phenyl-2-propen-1-one (3a-j, in high yields and in a few minutes, and the later compounds were treated with hydrazine hydrate according to Michael addition reaction to afford a new biolological active target compounds (4a-j and (5a-j. Furthermore, The structures of the newly synthesized compounds were confirmed by FT-IR, 13C-NMR,13C-DEPT & 1H-NMR spectral data. The chalcone and pyrazoline derivatives were evaluated for their anti bacterial activity against Escherichia coli as gram negative and Staphylococcus aureus as gram positive, the results showed significant activity against both types of bacteria.

Plant-Derived Polyphenols Interact with Staphylococcal Enterotoxin A and Inhibit Toxin Activity.

Science.gov (United States)

Shimamura, Yuko; Aoki, Natsumi; Sugiyama, Yuka; Tanaka, Takashi; Murata, Masatsune; Masuda, Shuichi

2016-01-01

This study was performed to investigate the inhibitory effects of 16 different plant-derived polyphenols on the toxicity of staphylococcal enterotoxin A (SEA). Plant-derived polyphenols were incubated with the cultured Staphylococcus aureus C-29 to investigate the effects of these samples on SEA produced from C-29 using Western blot analysis. Twelve polyphenols (0.1-0.5 mg/mL) inhibited the interaction between the anti-SEA antibody and SEA. We examined whether the polyphenols could directly interact with SEA after incubation of these test samples with SEA. As a result, 8 polyphenols (0.25 mg/mL) significantly decreased SEA protein levels. In addition, the polyphenols that interacted with SEA inactivated the toxin activity of splenocyte proliferation induced by SEA. Polyphenols that exerted inhibitory effects on SEA toxic activity had a tendency to interact with SEA. In particular, polyphenol compounds with 1 or 2 hexahydroxydiphenoyl groups and/or a galloyl group, such as eugeniin, castalagin, punicalagin, pedunculagin, corilagin and geraniin, strongly interacted with SEA and inhibited toxin activity at a low concentration. These polyphenols may be used to prevent S. aureus infection and staphylococcal food poisoning.

Plant-Derived Polyphenols Interact with Staphylococcal Enterotoxin A and Inhibit Toxin Activity.

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Yuko Shimamura

Full Text Available This study was performed to investigate the inhibitory effects of 16 different plant-derived polyphenols on the toxicity of staphylococcal enterotoxin A (SEA. Plant-derived polyphenols were incubated with the cultured Staphylococcus aureus C-29 to investigate the effects of these samples on SEA produced from C-29 using Western blot analysis. Twelve polyphenols (0.1-0.5 mg/mL inhibited the interaction between the anti-SEA antibody and SEA. We examined whether the polyphenols could directly interact with SEA after incubation of these test samples with SEA. As a result, 8 polyphenols (0.25 mg/mL significantly decreased SEA protein levels. In addition, the polyphenols that interacted with SEA inactivated the toxin activity of splenocyte proliferation induced by SEA. Polyphenols that exerted inhibitory effects on SEA toxic activity had a tendency to interact with SEA. In particular, polyphenol compounds with 1 or 2 hexahydroxydiphenoyl groups and/or a galloyl group, such as eugeniin, castalagin, punicalagin, pedunculagin, corilagin and geraniin, strongly interacted with SEA and inhibited toxin activity at a low concentration. These polyphenols may be used to prevent S. aureus infection and staphylococcal food poisoning.

Synthesis and Herbicidal Activity of New Hydrazide and Hydrazonoyl Derivatives

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František Šeršeň

2015-08-01

Full Text Available Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and growth of the green algae Chlorella vulgaris. IC50 values of these compounds varied in wide range, from a strong to no inhibitory effect. EPR spectroscopy showed that the active compounds interfered with intermediates Z•/D•, which are localized on the donor side of photosystem II. Fluorescence spectroscopy suggested that the mechanism of inhibitory action of the prepared compounds possibly involves interactions with aromatic amino acids present in photosynthetic proteins.

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

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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.

Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity.

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Sang-Ngern, Mayuramas; Youn, Ui Joung; Park, Eun-Jung; Kondratyuk, Tamara P; Simmons, Charles J; Wall, Marisa M; Ruf, Michael; Lorch, Sam E; Leong, Ethyn; Pezzuto, John M; Chang, Leng Chee

2016-06-15

Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8μM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6μM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity.

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Li, Qing; Sun, Xueqi; Gu, Guodong; Guo, Zhanyong

2018-03-28

Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating "click reaction" with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC 50 radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

Synthesis and Antimicrobial Activities of Some New 1,2,4-Triazole Derivatives

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Hakan Bektaş

2010-04-01

Full Text Available Some novel 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazol-3-one (3, 6, 8, 9 derivatives and or 3-(4-methylphenyl[1,2,4]triazolo[3,4-b][1,3]benzoxazole (5 were synthesized from the reaction of various ester ethoxycarbonylhydrazones (1a-e with several primary amines. The synthesis of 4-amino-5-(4-chlorophenyl-2-[(5-mercapto-1,3,4-oxadiazol-2-ylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (13 was performed starting from 4-Amino-5-(4-chlorophenyl-2,4-dihydro-3H-1,2,4-triazol-3-one (2 by four steps; then 13 was converted to the corresponding Schiff base (14 by using 4-methoxybenzaldehyde. Finally, two Mannich base derivatives of 14 were obtained by using morpholine or methyl piperazine as amine component. All newly synthesized compounds were screened for their antimicrobial activities and some of which were found to possess good or moderate activities against the test microorganisms.

Membrane curvature stress and antibacterial activity of lactoferricin derivatives.

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Zweytick, Dagmar; Tumer, Sabine; Blondelle, Sylvie E; Lohner, Karl

2008-05-02

We have studied correlation of non-lamellar phase formation and antimicrobial activity of two cationic amphipathic peptides, termed VS1-13 and VS1-24 derived from a fragment (LF11) of human lactoferricin on Escherichia coli total lipid extracts. Compared to LF11, VS1-13 exhibits minor, but VS1-24 significantly higher antimicrobial activity. X-ray experiments demonstrated that only VS1-24 decreased the onset of cubic phase formation of dispersions of E. coli lipid extracts, significantly, down to physiological relevant temperatures. Cubic structures were identified to belong to the space groups Pn3m and Im3m. Formation of latter is enhanced in the presence of VS1-24. Additionally, the presence of this peptide caused membrane thinning in the fluid phase, which may promote cubic phase formation. VS1-24 containing a larger hydrophobic volume at the N-terminus than its less active counterpart VS1-13 seems to increase curvature stress in the bilayer and alter the behaviour of the membrane significantly enhancing disruption.

Octulosonic acid derivatives from Roman chamomile (Chamaemelum nobile) with activities against inflammation and metabolic disorder.

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Zhao, Jianping; Khan, Shabana I; Wang, Mei; Vasquez, Yelkaira; Yang, Min Hye; Avula, Bharathi; Wang, Yan-Hong; Avonto, Cristina; Smillie, Troy J; Khan, Ikhlas A

2014-03-28

Six new octulosonic acid derivatives (1-6) were isolated from the flower heads of Roman chamomile (Chamaemelum nobile). Their structures were elucidated by means of spectroscopic interpretation. The biological activity of the isolated compounds was evaluated toward multiple targets related to inflammation and metabolic disorder such as NAG-1, NF-κB, iNOS, ROS, PPARα, PPARγ, and LXR. Similar to the action of NSAIDs, all the six compounds (1-6) increased NAG-1 activity 2-3-fold. They also decreased cellular oxidative stress by inhibiting ROS generation. Compounds 3, 5, and 6 activated PPARγ 1.6-2.1-fold, while PPARα was activated 1.4-fold by compounds 5 and 6 only. None of the compounds showed significant activity against iNOS or NF-κB. This is the first report of biological activity of octulosonic acid derivatives toward multiple pathways related to inflammation and metabolic disorder. The reported anti-inflammatory, hypoglycemic, antiedemic, and antioxidant activities of Roman chamomile could be partly explained as due to the presence of these constituents.

C60-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

International Nuclear Information System (INIS)

Xufeng Liu; Wenchao Guan; Wengshan Ke

2007-01-01

C 60 -based ebselen derivative 3 was synthesized through Bingel cyclopropanation of C 60 with the ebselen malonate 2. Compound 3 was obtained in 42% yield (based on consumed C 60 ) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2aminoethoxy)ethanol. Its structure was confirmed by 1H NMR, 13 C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C 60 derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 μmol L -1 ). Cell viabilities of the four treated groups were estimated by LDH (lactic dehydrogenase) leakage and MTT (3-(4, 5-dimethylthiazole-2yl)-2,5-diphenyl-tetrazolium bromide) assays. Results showed that the antioxidative and protective activities of C 60 -based ebselen derivative 3 against H 2 O 2 -mediated neuronal injury (MTT(OD) 0.364 ± 0.028; LDH release (UL -1 ) 4.66 ± 0.28) were significantly higher than those of C 6 )0 derivative 4 (MTT(OD) 0.324 ± 0.025; LDH release (UL -1 ) 5.39 ± 0.17), ebselen derivative 2 (MTT(OD) 0.294 ± 0.021; LDH release (UL -1 ) 5.71 ± 0.27), and the mixture of 4 and 2 (MTT(OD) 0.310 ± 0.018; LDH release (UL -1 ) 5.54 ±0.39). These findings demonstrated that the combination of two molecular units with similar biological activities (C 60 and ebselen) may be a desirable way of obtaining new and more biologically effective C 60 -based compounds. (author)

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

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Muniyan, Sakthivel; Chou, Yu-Wei; Ingersoll, Matthew A; Devine, Alexus; Morris, Marisha; Odero-Marah, Valerie A; Khan, Shafiq A; Chaney, William G; Bu, Xiu R; Lin, Ming-Fong

2014-10-10

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antimicrobial Activity of Some Thiourea Derivatives and Their Nickel and Copper Complexes

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Cevdet Akbay

2009-01-01

Full Text Available Five thiourea derivative ligands and their Ni2+ and Cu2+ complexes have been synthesized. The compounds were screened for their in vitro anti-bacterial activity using Gram-positive bacteria (two different standard strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Bacillus cereus and Gram-negative bacteria (Esherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Proteus vulgaris, Enterobacter aerogenes and in vitro anti-yeast activity (Candida albicans, Candida krusei, Candida glabrata, Candida tropicalis, Candida parapsilosis. The minimum inhibitory concentration was determined for all ligands and their complexes. In vitro anti-yeast activity of both ligands and their metal complexes is greater than their in vitro anti-bacterial activity. The effect of the structure of the investigated compounds on the antimicrobial activity is discussed.

Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2

International Nuclear Information System (INIS)

Miao, H.-Q.; Hu, Kun; Jimenez, Xenia; Navarro, Elizabeth; Zhang, Haifan; Lu Dan; Ludwig, Dale L.; Balderes, Paul; Zhu Zhenping

2006-01-01

Compelling evidence suggest that vascular endothelial growth factor (VEGF) and its receptors, especially receptor 2 (VEGFR2, or kinase insert domain-containing receptor, KDR), play a critical role in angiogenesis under both physiological and pathological conditions, including cancer and angiogenic retinopathies such as age-related macular degeneration (AMD). To this end, inhibition of angiogenesis with antagonists to either VEGF or KDR has yielded significant therapeutic efficacy both in preclinical studies in animal models and in clinical trials in patients with cancer and AMD. We previously reported the identification of a high affinity, fully human anti-KDR antibody fragment, 1121B Fab, through a highly stringent affinity maturation process with a Fab originally isolated from a naive human antibody phage display library. In this study, we demonstrate that 1121B Fab is able to strongly block KDR/VEGF interaction, resulting in potent inhibition of an array of biological activities of VEGF, including activation of the receptor and its signaling pathway, intracellular calcium mobilization, and migration and proliferation of endothelial cells. Taken together, our data lend strong support to the further development of 1121B Fab fragment as an anti-angiogenesis agent in both cancer and angiogenic retinopathies

Detection of transketolase in bone marrow-derived insulin-producing cells: benfotiamine enhances insulin synthesis and glucose metabolism.

Science.gov (United States)

Oh, Seh-Hoon; Witek, Rafal P; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E

2009-01-01

Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the proliferation of insulinoma cell line, INS-1; however, when INS-1 cells were cultured with oxythiamine, an inhibitor of TK, cell proliferation was suppressed. Treatment with benfotiamine activated glucose metabolism in INS-1 cells in high-glucose culture conditions, and appeared to maximize the BM-derived IPCs ability to synthesize insulin. Benfotiamine was not shown to induce the glucose receptor Glut-2, however it was shown to activate glucokinase, the enzyme responsible for conversion of glucose to glucose-6-phosphate. Furthermore, benfotiamine-treated groups showed upregulation of the downstream glycolytic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH). However, in cells where the pentose phosphate pathway was blocked by oxythiamine treatment, there was a clear downregulation of Glut-2, glucokinase, insulin, and GAPDH. When benfotiamine was used to treat mice transplanted with BM-derived IPCs transplanted, their glucose level was brought to a normal range. The glucose challenge of normal mice treated with benfotiamine lead to rapidly normalized blood glucose levels. These results indicate that benfotiamine activates glucose metabolism and insulin synthesis to prevent glucose toxicity caused by high concentrations of blood glucose in diabetes mellitus.

Detection of Transketolase in Bone Marrow—Derived Insulin-Producing Cells: Benfotiamine Enhances Insulin Synthesis and Glucose Metabolism

Science.gov (United States)

Witek, Rafal P.; Bae, Si-Hyun; Darwiche, Houda; Jung, Youngmi; Pi, Liya; Brown, Alicia; Petersen, Bryon E.

2009-01-01

Adult bone marrow (BM)-derived insulin-producing cells (IPCs) are capable of regulating blood glucose levels in chemically induced hyperglycemic mice. Using cell transplantation therapy, fully functional BM-derived IPCs help to mediate treatment of diabetes mellitus. Here, we demonstrate the detection of the pentose phosphate pathway enzyme, transketolase (TK), in BM-derived IPCs cultured under high-glucose conditions. Benfotiamine, a known activator of TK, was not shown to affect the proliferation of insulinoma cell line, INS-1; however, when INS-1 cells were cultured with oxythiamine, an inhibitor of TK, cell proliferation was suppressed. Treatment with benfotiamine activated glucose metabolism in INS-1 cells in high-glucose culture conditions, and appeared to maximize the BM-derived IPCs ability to synthesize insulin. Benfotiamine was not shown to induce the glucose receptor Glut-2, however it was shown to activate glucokinase, the enzyme responsible for conversion of glucose to glucose-6-phosphate. Furthermore, benfotiamine-treated groups showed upregulation of the downstream glycolytic enzyme, glyceraldehyde phosphate dehydrogenase (GAPDH). However, in cells where the pentose phosphate pathway was blocked by oxythiamine treatment, there was a clear downregulation of Glut-2, glucokinase, insulin, and GAPDH. When benfotiamine was used to treat mice transplanted with BM-derived IPCs transplanted, their glucose level was brought to a normal range. The glucose challenge of normal mice treated with benfotiamine lead to rapidly normalized blood glucose levels. These results indicate that benfotiamine activates glucose metabolism and insulin synthesis to prevent glucose toxicity caused by high concentrations of blood glucose in diabetes mellitus. PMID:18393672

Steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone: A convenient synthesis, antiproliferation activity, structure-activity relationships, and role of heterocyclic moiety

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Ke, Shaoyong; Shi, Liqiao; Zhang, Zhigang; Yang, Ziwen

2017-01-01

A series of steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone were designed and prepared by a convenient heterocyclization reaction. The in vitro anticancer activities for these obtained compounds were evaluated against human cancer cell lines (HepG2, Huh-7, and SGC-7901), which demonstrated that some of these heterocyclic pyrimidine derivatives exhibited significantly good cytotoxic activities against all tested cell lines compared with 5-fluorouracil (5-FU), especially, compound 3b exhibited high potential growth inhibitory activities against all tested cell lines with the IC50 values of 5.41 ± 1.34, 5.65 ± 1.02 and 10.64 ± 1.49 μM, respectively, which might be used as promising lead scaffold for discovery of novel anticancer agents. PMID:28290501

Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil

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Khoshayand Mohammad

2012-07-01

Full Text Available Abstract Background and the purpose of the study Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In the present investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions was investigated. Methods 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substituted benzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC in dimethyl formamide (DMF in the presence of the potassium carbonate followed by hydrolysis of the blocking group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29 cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and percent of the dead cells using propidium iodide(PI-digitonine assay and results were used to calculate the corresponding IC50 values. Radiosensitization experiments were carried out by irradiation of the incubations with a 60Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively. Results and major conclusion Findings of the present study

Spin labeled amino acid nitrosourea derivatives--synthesis and antitumour activity.

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Zheleva, A; Raikov, Z; Ilarionova, M; Todorov, D

1995-01-01

The synthesis of three spin labeled derivatives of N-[N'-(chloroethyl)-N'-nitrosocarbamoyl] amino acids is reported. The new nitrosoureas are obtained by condensation of the corresponding N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl] amino acid with 2,2,6,6-tetramethyl-1-oxyl-4-aminopiperidine using dicyclohexylcarbodiimide. Their chemical structures are confirmed by elemental analysis, IR, MS, and EPR spectroscopy. All newly synthesized compounds showed high antitumour activity against the lymphoid leukemia L1210 in BDF1 mice.

Quantitative structure-activity relationship of some 1-benzylbenzimidazole derivatives as antifungal agents

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Podunavac-Kuzmanović Sanja O.

2007-01-01

Full Text Available In the present study, the antifungal activity of some 1-benzylbenzimidazole derivatives against yeast Saccharomyces cerevisiae was investigated. The tested benzimidazoles displayed in vitro antifungal activity and minimum inhibitory concentration (MIC was determined for all the compounds. Quantitative structure-activity relationship (QSAR has been used to study the relationships between the antifungal activity and lipophilicity parameter, logP, calculated by using CS Chem-Office Software version 7.0. The results are discussed on the basis of statistical data. The best QSAR model for prediction of antifungal activity of the investigated series of benzimidazoles was developed. High agreement between experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antifungal activity of this class of compounds, which simplify design of new biologically active molecules.

Egr-1 activation by cancer-derived extracellular vesicles promotes endothelial cell migration via ERK1/2 and JNK signaling pathways.

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Yae Jin Yoon

Full Text Available Various mammalian cells, including cancer cells, shed extracellular vesicles (EVs, also known as exosomes and microvesicles, into surrounding tissues. These EVs play roles in tumor growth and metastasis by promoting angiogenesis. However, the detailed mechanism of how cancer-derived EVs elicit endothelial cell activation remains unknown. Here, we provide evidence that early growth response-1 (Egr-1 activation in endothelial cells is involved in the angiogenic activity of colorectal cancer cell-derived EVs. Both RNA interference-mediated downregulation of Egr-1 and ERK1/2 or JNK inhibitor significantly blocked EV-mediated Egr-1 activation and endothelial cell migration. Furthermore, lipid raft-mediated endocytosis inhibitor effectively blocked endothelial Egr-1 activation and migration induced by cancer-derived EVs. Our results suggest that Egr-1 activation in endothelial cells may be a key mechanism involved in the angiogenic activity of cancer-derived EVs. These findings will improve our understanding regarding the proangiogenic activities of EVs in diverse pathological conditions including cancer, cardiovascular diseases, and neurodegenerative diseases.

Antitumoral, antileishmanial and antimalarial activity of pentacyclic 1,4-naphthoquinone derivatives

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Silva, Alcides J.M. da; Netto, Chaquip D; Costa, Paulo R.R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nucleo de Pesquisas de Produtos Naturais. Lab. de Quimica Bioorganica; Pacienza-Lima, Wallace; Rossi-Bergmann, Bartira; Maurel, Severine; Valentin, Alexis; Costa, Paulo R.R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho; Torres-Santos, Eduardo Caio [Instituto Oswaldo Cruz, Rio de Janeiro, RJ (Brazil). Lab. de Bioquimica de Tripanosomatideos; Maurel, Severine; Valentin, Alexis [Universite Paul Sabatier, Toulouse (France). Faculte de Pharmacie. Pharmacochimie des Substances Naturelles et Pharmacophores Redox

2009-07-01

Pterocarpanquinones 8a-c, previously synthesized in our laboratory, and an homologous series of derivatives, compounds 9a-c prepared in this work, were evaluated on breast cancer cells (MCF-7) and on the parasites Leishmania amazonensis and Plasmodium falciparum, in culture. Compounds 8a-c were more potent than 9a-c on tumor cells and Leishmania amazonensis. On the other hand, 9a-c showed to be more active on Plasmodium falciparum. All the compounds studied were bioselective, presenting negligible cytotoxicity against fresh murine lymphocytes and human lymphocytes activated by the mitogen phytohemagglutinin (PHA). (author)

Antitumoral, antileishmanial and antimalarial activity of pentacyclic 1,4-naphthoquinone derivatives

International Nuclear Information System (INIS)

Silva, Alcides J.M. da; Netto, Chaquip D.; Costa, Paulo R.R.; Pacienza-Lima, Wallace; Rossi-Bergmann, Bartira; Maurel, Severine; Valentin, Alexis; Costa, Paulo R.R.; Torres-Santos, Eduardo Caio; Maurel, Severine; Valentin, Alexis

2009-01-01

Pterocarpanquinones 8a-c, previously synthesized in our laboratory, and an homologous series of derivatives, compounds 9a-c prepared in this work, were evaluated on breast cancer cells (MCF-7) and on the parasites Leishmania amazonensis and Plasmodium falciparum, in culture. Compounds 8a-c were more potent than 9a-c on tumor cells and Leishmania amazonensis. On the other hand, 9a-c showed to be more active on Plasmodium falciparum. All the compounds studied were bioselective, presenting negligible cytotoxicity against fresh murine lymphocytes and human lymphocytes activated by the mitogen phytohemagglutinin (PHA). (author)

Tolerance, immunocompetence, and secondary disease in fully allogeneic radiation chimeras

International Nuclear Information System (INIS)

Rayfield, L.S.; Brent, L.

1983-01-01

The aim of this study was to ascertain the extent to which secondary disease and mortality in fully allogeneic chimeras (C57BL leads to CBA) is caused (if at all) by a delayed graft-versus-host reaction. Adult CBA males were thymectomized, irradiated, and reconstituted with T-lymphocyte-depleted C57BL or CBA bone marrow cells (BMC), followed three weeks after irradiation by implantation under the kidney capsule of thymic lobes from C57BL or CBA fetal or adult donors. These mice were observed for the development of secondary disease for periods in excess of 250 days, and they were examined at 5 weeks or 4 months for T lymphocyte reactivity and tolerance to alloantigens, using the cell-mediated lympholysis assay (CML). The following results were obtained. First, removal of T lymphocytes with anti-Thy 1 antibody and complement from allogeneic bone marrow did not prevent wasting and eventual death, although it prolonged the lifespan of mice substantially. Second, T lymphocytes generated from bone marrow-derived precursor cells became tolerant of the histocompatibility antigens of the thymus donor strain but remained normally reactive to third-party antigens. Third, allogeneic radiation chimeras did not survive as well as animals reconstituted with syngeneic cells, even when they were demonstrably tolerant in CML. Fourth, C57BL BMC maturing in a CBA host equipped with a C57BL thymus graft did not become tolerant of host antigens, indicating that extra-thymic tolerance does not occur in fully allogeneic--as opposed to semiallogeneic--chimeras. It is argued that the function of B lymphocytes and/or accessory cells is impaired in fully allogeneic radiation chimeras, and that the mortality observed was directly related to the resulting immunodeficiency. The relevance of the results described in this paper to clinical bone marrow transplantation is discussed

Removal potential of toxic 2378-substituted PCDD/F from incinerator flue gases by waste-derived activated carbons.

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Hajizadeh, Yaghoub; Onwudili, Jude A; Williams, Paul T

2011-06-01

The application of activated carbons has become a commonly used emission control protocol for the removal or adsorption of persistent organic pollutants from the flue gas streams of waste incinerators. In this study, the 2378-substituted PCDD/F removal efficiency of three types of activated carbons derived from the pyrolysis of refuse derived fuel, textile waste and scrap tyre was investigated and compared with that of a commercial carbon. Experiments were carried out in a laboratory scale fixed-bed reactor under a simulated flue gas at 275°C with a reaction period of four days. The PCDD/F in the solid matrices and exhaust gas, were analyzed using gas chromatography coupled with a triple quadrupole mass spectrometer. In the absence of activated carbon adsorbent, there was a significant increase in the concentration of toxic PCDD/F produced in the reacted flyash, reaching up to 6.6 times higher than in the raw flyash. In addition, there was a substantial release of PCDD/F into the gas phase, which was found in the flue gas trapping system. By application of the different commercial, refuse derived fuel, textile and tyre activated carbons the total PCDD/F toxic equivalent removal efficiencies in the exhaust gas stream were 58%, 57%, 64% and 52%, respectively. In general, the removal of the PCDDs was much higher with an average of 85% compared to PCDFs at 41%. Analysis of the reacted activated carbons showed that there was some formation of PCDD/F, for instance, a total of 60.6 μg I-TEQ kg(-1) toxic PCDD/F was formed in the refuse derived fuel activated carbon compared to 34 μg I-TEQ kg(-1) in the commercial activated carbon. The activated carbons derived from the pyrolysis of waste, therefore, showed good potential as a control material for PCDD/F emissions in waste incinerator flue gases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structure-activity relationships of bumetanide derivatives: correlation between diuretic activity in dogs and inhibition of the human NKCC2A transporter.

Science.gov (United States)

Lykke, Kasper; Töllner, Kathrin; Römermann, Kerstin; Feit, Peter W; Erker, Thomas; MacAulay, Nanna; Löscher, Wolfgang

2015-06-23

The N-K-Cl cotransporters (NKCCs) mediate the coupled, electroneutral movement of Na + , K + and Cl - ions across cell membranes. There are two isoforms of this cation co-transporter, NKCC1 and NKCC2. NKCC2 is expressed primarily in the kidney and is the target of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. In this study, the effect of a series of diuretically active bumetanide derivatives was investigated on human NKCC2 variant A (hNKCC2A) expressed in Xenopus laevis oocytes. Bumetanide blocked hNKCC2A transport with an IC 50 of 4 μM. There was good correlation between the diuretic potency of bumetanide and its derivatives in dogs and their inhibition of hNKCC2A (r 2 = 0.817; P human NKCC2 splice variants, and may lead to the discovery of novel high-ceiling diuretics. © 2015 The British Pharmacological Society.

A highly linear fully integrated powerline filter for biopotential acquisition systems.

Science.gov (United States)

Alzaher, Hussain A; Tasadduq, Noman; Mahnashi, Yaqub

2013-10-01

Powerline interference is one of the most dominant problems in detection and processing of biopotential signals. This work presents a new fully integrated notch filter exhibiting high linearity and low power consumption. High filter linearity is preserved utilizing active-RC approach while IC implementation is achieved through replacing passive resistors by R-2R ladders achieving area saving of approximately 120 times. The filter design is optimized for low power operation using an efficient circuit topology and an ultra-low power operational amplifier. Fully differential implementation of the proposed filter shows notch depth of 43 dB (78 dB for 4th-order) with THD of better than -70 dB while consuming about 150 nW from 1.5 V supply.

Natural gas adsorption on biomass derived activated carbons: A mini review

Directory of Open Access Journals (Sweden)

Hamza Usman D.

2016-01-01

Full Text Available Activated carbon materials are good candidates for natural gas storage due excellent textural properties that are easy to enhance and modify. Natural gas is much cleaner fuel than coal and other petroleum derivatives. Storage of natural gas on porous sorbents at lower pressure is safer and cheaper compared to compressed and liquefied natural gas. This article reviews some works conducted on natural gas storage on biomass based activated carbon materials. Methane storage capacities and deliveries of the various sorbents were given. The effect of factors such as surface area, pore characteristic, heat of adsorption, packing density on the natural gas storage capacity on the activated carbons are discussed. Challenges, improvements and future directions of natural gas storage on porous carbonaceous materials are highlighted.

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

Science.gov (United States)

McAllister, Sean D; Soroceanu, Liliana; Desprez, Pierre-Yves

2015-06-01

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ(9)-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors. For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer. This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells. We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.

Antiplasmodial and antimalarial activities of quinolone derivatives: An overview.

Science.gov (United States)

Fan, Yi-Lei; Cheng, Xiang-Wei; Wu, Jian-Bing; Liu, Min; Zhang, Feng-Zhi; Xu, Zhi; Feng, Lian-Shun

2018-02-25

Malaria remains one of the most deadly infectious diseases globally. Considering the growing spread of resistance, development of new and effective antimalarials remains an urgent priority. Quinolones, which are emerged as one of the most important class of antibiotics in the treatment of various bacterial infections, showed potential in vitro antiplasmodial and in vivo antimalarial activities, making them promising candidates for the chemoprophylaxis and treatment of malaria. This review presents the current progresses and applications of quinolone-based derivatives as potential antimalarials to pave the way for the development of new antimalarials. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

CO{sub 2} capture using some fly ash-derived carbon materials

Energy Technology Data Exchange (ETDEWEB)

A. Arenillas; K.M. Smith; T.C. Drage; C.E. Snape [University of Nottingham, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

2005-12-01

Adsorption is considered to be one of the more promising technologies for capturing CO{sub 2} from flue gases. For post-combustion capture, the success of such an approach is however dependent on the development of an adsorbent that can operate competitively at relatively high temperatures. In this work, low cost carbon materials derived from fly ash, are presented as effective CO{sub 2} sorbents through impregnation these with organic bases, for example, polyethylenimine aided by polyethylene glycol. The results show that for samples derived from a fly ash carbon concentrate, the CO{sub 2} adsorption capacities were relatively high (up to 4.5 wt%) especially at high temperatures (75{sup o}C), where commercial active carbons relying on physi-sorption have low capacities. The addition of PEG improves the adsorption capacity and reduces the time taken for the sample to reach the equilibrium. No CO{sub 2} seems to remain after desorption, suggesting that the process is fully reversible. 24 refs., 6 figs., 2 tabs.

Imidazopyridine-5,6,7,8-tetrahydro-8-quinolinamine derivatives with potent activity against HIV-1.

Science.gov (United States)

Gudmundsson, Kristjan S; Boggs, Sharon D; Catalano, John G; Svolto, Angilique; Spaltenstein, Andrew; Thomson, Michael; Wheelan, Pat; Jenkinson, Stephen

2009-11-15

Synthesis of several novel imidazopyridine-5,6,7,8-tetrahydro-8-quinolinamine derivatives with potent activity against HIV are described. Synthetic approaches allowing for variation of the substitution pattern are outlined and resulting changes in antiviral activity and pharmacokinetics are highlighted. Several compounds with low nanomolar anti-HIV activity and oral bioavailability are described.

Interplay of activation kinetics and the derivative conductance determines resonance properties of neurons

Science.gov (United States)

Pena, Rodrigo F. O.; Ceballos, Cesar C.; Lima, Vinicius; Roque, Antonio C.

2018-04-01

In a neuron with hyperpolarization activated current (Ih), the correct input frequency leads to an enhancement of the output response. This behavior is known as resonance and is well described by the neuronal impedance. In a simple neuron model we derive equations for the neuron's resonance and we link its frequency and existence with the biophysical properties of Ih. For a small voltage change, the component of the ratio of current change to voltage change (d I /d V ) due to the voltage-dependent conductance change (d g /d V ) is known as derivative conductance (GhDer). We show that both GhDer and the current activation kinetics (characterized by the activation time constant τh) are mainly responsible for controlling the frequency and existence of resonance. The increment of both factors (GhDer and τh) greatly contributes to the appearance of resonance. We also demonstrate that resonance is voltage dependent due to the voltage dependence of GhDer. Our results have important implications and can be used to predict and explain resonance properties of neurons with the Ih current.

Platelet-Derived Short-Chain Polyphosphates Enhance the Inactivation of Tissue Factor Pathway Inhibitor by Activated Coagulation Factor XI.

Directory of Open Access Journals (Sweden)

Cristina Puy

Full Text Available Factor (F XI supports both normal human hemostasis and pathological thrombosis. Activated FXI (FXIa promotes thrombin generation by enzymatic activation of FXI, FIX, FX, and FV, and inactivation of alpha tissue factor pathway inhibitor (TFPIα, in vitro. Some of these reactions are now known to be enhanced by short-chain polyphosphates (SCP derived from activated platelets. These SCPs act as a cofactor for the activation of FXI and FV by thrombin and FXIa, respectively. Since SCPs have been shown to inhibit the anticoagulant function of TFPIα, we herein investigated whether SCPs could serve as cofactors for the proteolytic inactivation of TFPIα by FXIa, further promoting the efficiency of the extrinsic pathway of coagulation to generate thrombin.Purified soluble SCP was prepared by size-fractionation of sodium polyphosphate. TFPIα proteolysis was analyzed by western blot. TFPIα activity was measured as inhibition of FX activation and activity in coagulation and chromogenic assays. SCPs significantly accelerated the rate of inactivation of TFPIα by FXIa in both purified systems and in recalcified plasma. Moreover, platelet-derived SCP accelerated the rate of inactivation of platelet-derived TFPIα by FXIa. TFPIα activity was not affected by SCP in recalcified FXI-depleted plasma.Our data suggest that SCP is a cofactor for TFPIα inactivation by FXIa, thus, expanding the range of hemostatic FXIa substrates that may be affected by the cofactor functions of platelet-derived SCP.

Synthesis and antifungal activity of new salicylic acid derivatives

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Wodnicka Alicja

2017-03-01

Full Text Available A simple one-step procedure for synthesis of 1-methoxy-1-oxoalkan-2-yl salicylates and 1-methoxy-1-oxoalkan-2-yl 2-[(1-methoxy-1-oxoalkan-2-yloxy]benzoates by reaction of salicylic acid with several methyl 2-bromoalkanoates was developed. The reactions were carried out in N,N-dimethylformamide (DMF in the presence of anhydrous potassium carbonate. Conditions for regioselective synthesis of target compounds were established. The developed procedure could be easily applied in the industrial production process. The new salicylic acid derivatives were obtained with satisfactory yields and were characterized by MS and 1H NMR spectra. The fungicidal activity of the prepared compounds was tested in vitro against seven species of plant pathogenic fungi. The best results were observed for 1-methoxy-1-oxoalkan-2-yl salicylates which showed moderate or good activity against Botrytis cinerea and Rhizoctonia solani.

Towards a Scalable Fully-Implicit Fully-coupled Resistive MHD Formulation with Stabilized FE Methods

Energy Technology Data Exchange (ETDEWEB)

Shadid, J N; Pawlowski, R P; Banks, J W; Chacon, L; Lin, P T; Tuminaro, R S

2009-06-03

This paper presents an initial study that is intended to explore the development of a scalable fully-implicit stabilized unstructured finite element (FE) capability for low-Mach-number resistive MHD. The discussion considers the development of the stabilized FE formulation and the underlying fully-coupled preconditioned Newton-Krylov nonlinear iterative solver. To enable robust, scalable and efficient solution of the large-scale sparse linear systems generated by the Newton linearization, fully-coupled algebraic multilevel preconditioners are employed. Verification results demonstrate the expected order-of-acuracy for the stabilized FE discretization of a 2D vector potential form for the steady and transient solution of the resistive MHD system. In addition, this study puts forth a set of challenging prototype problems that include the solution of an MHD Faraday conduction pump, a hydromagnetic Rayleigh-Bernard linear stability calculation, and a magnetic island coalescence problem. Initial results that explore the scaling of the solution methods are presented on up to 4096 processors for problems with up to 64M unknowns on a CrayXT3/4. Additionally, a large-scale proof-of-capability calculation for 1 billion unknowns for the MHD Faraday pump problem on 24,000 cores is presented.

GC protein-derived macrophage-activating factor decreases ?-N-acetylgalactosaminidase levels in advanced cancer patients

OpenAIRE

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-01-01

?-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort ...

Activated carbon derived from waste coffee grounds for stable methane storage

International Nuclear Information System (INIS)

Kemp, K Christian; Baek, Seung Bin; Lee, Wang-Geun; Kim, Kwang S; Meyyappan, M

2015-01-01

An activated carbon material derived from waste coffee grounds is shown to be an effective and stable medium for methane storage. The sample activated at 900 °C displays a surface area of 1040.3 m"2 g"−"1 and a micropore volume of 0.574 cm"3 g"−"1 and exhibits a stable CH_4 adsorption capacity of ∼4.2 mmol g"−"1 at 3.0 MPa and a temperature range of 298 ± 10 K. The same material exhibits an impressive hydrogen storage capacity of 1.75 wt% as well at 77 K and 100 kPa. Here, we also propose a mechanism for the formation of activated carbon from spent coffee grounds. At low temperatures, the material has two distinct types with low and high surface areas; however, activation at elevated temperatures drives off the low surface area carbon, leaving behind the porous high surface area activated carbon. (paper)

Lysine and pipecolic acid and some of their derivatives show anticonvulsant activity, and stimulation of benzodiazepine receptor activity

International Nuclear Information System (INIS)

Chang, Yung-Feng; Gao, Xue-Min

1989-01-01

Benzodiazepines are one of the most widely prescribed drugs in the treatment of anxiety, epilepsy and muscle tension. The natural products lysine and pipecolic acid known to be present in the animal, plant and microorganism, have been shown to be anticonvulsant against pentetrazol (PTZ)-induced seizures in mice. Methyl and ethyl esters of L-lysine and the N-isopropanol derivative of pipecolic acid appear to increase the anticonvulsant potency of the parent compounds, presumably due to their increase in hydrophobicity. Lysine and pipecolic acid showed significant stimulation of specific [ 3 H]flunitrazepam (FZ) binding to mouse brain membranes. This stimulation was enhanced by chloride ions and stereospecific with L-isomer having higher effect. The dose-dependent anticonvulsant activity of lysine and pipecolic acid, and their stimulation of [ 3 H]FZ binding appear to be correlated. The antiepileptic activity lysine, pipecolic acid and their derivatives therefore may be mediated through the γ-aminobutyric acid-benzodiazepine receptor complex

Optical limiting properties of optically active phthalocyanine derivatives

Science.gov (United States)

Wang, Peng; Zhang, Shuang; Wu, Peiji; Ye, Cheng; Liu, Hongwei; Xi, Fu

2001-06-01

The optical limiting properties of four optically active phthalocyanine derivatives in chloroform solutions and epoxy resin thin plates were measured at 532 nm with 10 ns pulses. The excited state absorption cross-section σex and refractive-index cross-section σr were determined with the Z-scan technique. These chromophores possess larger σex than the ground state absorption cross-section σ0, indicating that they are the potential materials for reverse saturable absorption (RSA). The negative σr values of these chromophores add to the thermal contribution, producing a larger defocusing effect, which may be helpful in further enhancing their optical limiting performance. The optical limiting responses of the thin plate samples are stronger than those of the chloroform solutions.

Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides

Science.gov (United States)

van Dijk, Albert; van Eldik, Mandy; Veldhuizen, Edwin J. A.; Tjeerdsma-van Bokhoven, Hanne L. M.; de Zoete, Marcel R.; Bikker, Floris J.; Haagsman, Henk P.

2016-01-01

Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2)-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11) we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS). N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives. PMID:26848845

Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides.

Directory of Open Access Journals (Sweden)

Albert van Dijk

Full Text Available Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11 we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS. N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives.

Silica nanoparticles for the layer-by-layer assembly of fully electro-active cytochrome c multilayers

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Feifel Sven C

2011-12-01

influence of particle size are discussed. Conclusions This study demonstrates the ability to construct fully electro-active cyt c multilayer assemblies by using carboxy-modified silica nanoparticles. Thus it can be shown that functional, artificial systems can be build up following natural examples of protein arrangements. The absence of any conductive properties in the second building block clearly demonstrates that mechanisms for electron transfer through such protein multilayer assemblies is based on interprotein electron exchange, rather than on wiring of the protein to the electrode. The construction strategy of this multilayer system provides a new controllable route to immobilize proteins in multiple layers featuring direct electrochemistry without mediating shuttle molecules and controlling the electro-active amount by the number of deposition steps.

Synthesis of Novel (E) -α-(methoxyimino) Benzeneacetate Derivatives and their Fungicidal Activities

International Nuclear Information System (INIS)

Wang, X.; Chen, P.; Pang, Y.; Zhao, Z.; Wu, G.; Wang, H.

2015-01-01

In order to find novel strobilurin derivatives with good fungicidal activities, a series of (E)-α-(methoxyimino)benzeneacetate analogues containing 1,2,4-triazole Schiff base moiety were designed and synthesized. Their structures were confirmed by IR,1H-NMR, HRMS or elemental analyses. The antifungal activities indicated that compounds 6 showed moderate to good fungicidal activities against Rhizoctonia solani, Botrytis cinereapers, Fusarium graminearum and Blumeria graminis at the concentration 50 μ g/mL. For example, compounds 6e and 6h exhibited promising antifungal activity against Rhizoctonia solani, Botrytis cinereapers and Fusarium graminearum. Compounds 6g and 6j had higher fungicidal activities against Blumeria graminis at the concentration of 50 μ g/ml, inhibitory rate is 95.32 percentage and 89.67 percentage, respectively. (author)

Intracellular protein delivery activity of peptides derived from insulin-like growth factor binding proteins 3 and 5

International Nuclear Information System (INIS)

Goda, Natsuko; Tenno, Takeshi; Inomata, Kosuke; Shirakawa, Masahiro; Tanaka, Toshiki; Hiroaki, Hidekazu

2008-01-01

Insulin-like growth factor binding proteins (IGFBPs) have various IGF-independent cellular activities, including receptor-independent cellular uptake followed by transcriptional regulation, although mechanisms of cellular entry remain unclear. Herein, we focused on their receptor-independent cellular entry mechanism in terms of protein transduction domain (PTD) activity, which is an emerging technique useful for clinical applications. The peptides of 18 amino acid residues derived from IGFBP-3 and IGFBP-5, which involve heparin-binding regions, mediated cellular delivery of an exogenous protein into NIH3T3 and HeLa cells. Relative protein delivery activities of IGFBP-3/5-derived peptides were approximately 20-150% compared to that of the HIV-Tat peptide, a potent PTD. Heparin inhibited the uptake of the fusion proteins with IGFBP-3 and IGFBP-5, indicating that the delivery pathway is heparin-dependent endocytosis, similar to that of HIV-Tat. The delivery of GST fused to HIV-Tat was competed by either IGFBP-3 or IGFBP-5-derived synthetic peptides. Therefore, the entry pathways of the three PTDs are shared. Our data has shown a new approach for designing protein delivery systems using IGFBP-3/5 derived peptides based on the molecular mechanisms of IGF-independent activities of IGFBPs

Antioxidant and Antiplatelet Activities in Extracts from Green and Fully Ripe Tomato Fruits (Solanum lycopersicum and Pomace from Industrial Tomato Processing

Directory of Open Access Journals (Sweden)

Eduardo Fuentes

2013-01-01

Full Text Available The consumption of fruits and vegetables is accepted to be one of the strategies to reduce risk factors for these diseases. The aim of this study was to examine potential relationships between the antioxidant and the antiplatelet activities in green mature and fully ripe (red tomatoes and of lycopene-rich byproducts of tomato paste processing such as pomace. The total phenol content of tomato components was the highest in peels, pulp, and in the mucilaginous myxotesta covering the tomato seeds with values 36.9±0.8, 33.3±00.5, and 17.6±0.9 mg GAE/100 g, respectively (P<0.05. Tomato peels had the highest antioxidant activity, both, as measured by the FRAP (46.9±0.9 μmol Fe+2/g, P<0.05 and the DPPH assays (97.4±0.2%, 1000 μg/mL, P<0.05. Pomace extracts showed the highest antiplatelet activity induced by ADP, collagen, TRAP-6, and arachidonic acid. While the maturation stage of the tomato fruit affected the antioxidant effect, antiplatelet activity was independent of fruit ripeness. Finally, based on the present results, tomato and its byproducts may be considered as a valuable source of antioxidant and antiplatelet activities.

4'-Methyl derivatives of 5-MOP and 5-MOA: synthesis, photoreactivity, and photobiological activity.

Science.gov (United States)

Gia, O; Anselmo, A; Conconi, M T; Antonello, C; Uriarte, E; Caffieri, S

1996-10-25

The synthesis and photobiological activity of four new 4'-methyl derivatives of 5-MOP (5-methoxypsoralen) and 5-MOA (5-methoxyangelicin), i.e., 4,4'-dimethyl-5-methoxypsoralen, 3,4'-dimethyl-5-methoxypsoralen, 4,4'-dimethyl-5-methoxyangelicin, and 3,4'-dimethyl-5-methoxyangelicin, are described. All these compounds photobind efficiently to DNA. The DNA-photobinding process was investigated using various nucleic acid structures such as double-helix DNA, bacterial DNA, and synthetic polydeoxyribonucleotides. Photoreaction experiments showed that, unlike 8-MOP (8-methoxypsoralen) and 5-MOP, both angular derivatives bind thymine and cytosine with the same efficiency. The principal nucleoside-psoralen monoadducts were isolated and characterized after enzymatic digestion or acid hydrolysis. Biological activity studies revealed a good correlation with the extent of covalent photoaddition. Moreover, the two angular derivatives and the 4,4'-dimethyl-5-methoxypsoralen were unable to induce skin erythema, in striking contrast with the reference drugs, 8-MOP and 5-MOP; only the 3,4'-dimethyl-5-methoxypsoralen caused erythema, although to a substantially lower extent than that induced by the two parent compounds.

Monoalkylated barbiturate derivatives: X-ray crystal structure, theoretical studies, and biological activities

Science.gov (United States)

Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Islam, Mohammad Shahidul; Ghawas, Hussain Mansur; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

2017-08-01

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a-l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a-l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a-3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

Semi-synthesis and NMR spectral assignments of flavonoid and chalcone derivatives.

Science.gov (United States)

Kumar, Rohitesh; Lu, Yuting; Elliott, Alysha G; Kavanagh, Angela M; Cooper, Matthew A; Davis, Rohan A

2016-11-01

Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin (4) and 2',6'-dihydroxy-4'-methoxy-3',5'-dimethyl chalcone (7), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4'-triacetoxy jaceosidin (10), 5,7,4'-tripivaloyloxy jaceosidin (11), 5,7,4'-trimethoxy jaceosidin (12), 2',6'-diacetoxy-4'-methoxy-3',5'-dimethyl chalcone (13), 2'-hydroxy-4'-methoxy-6'-pivaloyloxy-3',5'-dimethyl chalcone (14), and 2'-hydroxy-4',6'-dimethoxy-3',5'-dimethyl chalcone (15) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14. The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin (4) and the acetylated derivative, 5,7,4'-triacetoxy jaceosidin (10), showed modest antibacterial activity (32-128 µg/ml) against Staphylococcus aureus strains. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A look-up table for fully developed film-boiling heat transfer

International Nuclear Information System (INIS)

Groeneveld, D.C.; Leung, L.K.H.; Vasic, A.Z.; Guo, Y.J.; Cheng, S.C.

2003-01-01

An improved look-up table for film-boiling heat-transfer coefficients has been derived for steam-water flow inside vertical tubes. Compared to earlier versions of the look-up table, the following improvements were made: - The database has been expanded significantly. The present database contains 77,234 film-boiling data points obtained from 36 sources. - The upper limit of the thermodynamic quality range was increased from 1.2 to 2.0. The wider range was needed as non-equilibrium effects at low flows can extend well beyond the point where the thermodynamic quality equals unity. - The surface heat flux has been replaced by the surface temperature as an independent parameter. - The new look-up table is based only on fully developed film-boiling data. - The table entries at flow conditions for which no data are available is based on the best of five different film-boiling prediction methods. The new film-boiling look-up table predicts the database for fully developed film-boiling data with an overall rms error in heat-transfer coefficient of 10.56% and an average error of 1.71%. A comparison of the prediction accuracy of the look-up table with other leading film-boiling prediction methods shows that the look-up table results in a significant improvement in prediction accuracy

A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

NARCIS (Netherlands)

Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell

New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis.

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Mariz Gomes da Silva, Luana Maria; de Oliveira, Jamerson Ferreira; Silva, Willams Leal; da Silva, Anekecia Lauro; de Almeida Junior, Antônio Sérgio Alves; Barbosa Dos Santos, Victor Hugo; Alves, Luiz Carlos; Brayner Dos Santos, Fábio André; Costa, Vlaudia Maria Assis; Aires, André de Lima; de Lima, Maria do Carmo Alves; Albuquerque, Monica Camelo Pessoa de Azevedo

2018-03-01

Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3-14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 μM and 83.3% at the concentration of 50 μM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs. Copyright © 2018 Elsevier B

Isolation, Purification, and Characterization of Five Active Diketopiperazine Derivatives from Endophytic Streptomyces SUK 25 with Antimicrobial and Cytotoxic Activities.

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Alshaibani, Muhanna; Zin, Noraziah; Jalil, Juriyati; Sidik, Nik; Ahmad, Siti Junaidah; Kamal, Nurkhalida; Edrada-Ebel, Ruangelie

2017-07-28

In our search for new sources of bioactive secondary metabolites from Streptomyces sp., the ethyl acetate extracts from endophytic Streptomyces SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic Streptomyces SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as Enterococcus raffinosus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter spp., and their cytotoxic activities against the human hepatoma (HepaRG) cell line. The production of secondary metabolites by this strain was optimized through Thornton's medium. Isolation, purification, and identification of the bioactive compounds were carried out using high-performance liquid chromatography, high-resolution mass liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance, and cryopreserved HepaRG cells were selected to test the cytotoxicity. The results showed that endophytic Streptomyces SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as cyclo -( L -Val- L -Pro), cyclo -( L -Leu- L -Pro), cyclo -( L -Phe- L -Pro), cyclo -( L -Val- L -Phe), and N -(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and Enterococcus raffinosus , with low toxicity against human hepatoma HepaRG cells. Endophytic Streptomyces SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line.

FOXOs modulate proteasome activity in human-induced pluripotent stem cells of Huntington's disease and their derived neural cells.

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Liu, Yanying; Qiao, Fangfang; Leiferman, Patricia C; Ross, Alan; Schlenker, Evelyn H; Wang, Hongmin

2017-11-15

Although it has been speculated that proteasome dysfunction may contribute to the pathogenesis of Huntington's disease (HD), a devastating neurodegenerative disorder, how proteasome activity is regulated in HD affected stem cells and somatic cells remains largely unclear. To better understand the pathogenesis of HD, we analyzed proteasome activity and the expression of FOXO transcription factors in three wild-type (WT) and three HD induced-pluripotent stem cell (iPSC) lines. HD iPSCs exhibited elevated proteasome activity and higher levels of FOXO1 and FOXO4 proteins. Knockdown of FOXO4 but not FOXO1 expression decreased proteasome activity. Following neural differentiation, the HD-iPSC-derived neural progenitor cells (NPCs) demonstrated lower levels of proteasome activity and FOXO expressions than their WT counterparts. More importantly, overexpression of FOXO4 but not FOXO1 in HD NPCs dramatically enhanced proteasome activity. When HD NPCs were further differentiated into DARPP32-positive neurons, these HD neurons were more susceptible to death than WT neurons and formed Htt aggregates under the condition of oxidative stress. Similar to HD NPCs, HD-iPSC-derived neurons showed reduced proteasome activity and diminished FOXO4 expression compared to WT-iPSC-derived neurons. Furthermore, HD iPSCs had lower AKT activities than WT iPSCs, whereas the neurons derived from HD iPSC had higher AKT activities than their WT counterparts. Inhibiting AKT activity increased both FOXO4 level and proteasome activity, indicating a potential role of AKT in regulating FOXO levels. These data suggest that FOXOs modulate proteasome activity, and thus represents a potentially valuable therapeutic target for HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synthesis, PASS-Predication and in Vitro Antimicrobial Activity of Benzyl 4-O-benzoyl-α-l-rhamnopyranoside Derivatives

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Mohammed Mahbubul Matin

2016-08-01

Full Text Available Benzyl α-l-rhamnopyranoside 4, obtained by both conventional and microwave assisted glycosidation techniques, was subjected to 2,3-O-isopropylidene protection to yield compound 5 which on benzoylation and subsequent deprotection of isopropylidene group gave the desired 4-O-benzoylrhamnopyranoside 7 in reasonable yield. Di-O-acetyl derivative of benzoate 7 was prepared to get newer rhamnopyranoside. The structure activity relationship (SAR of the designed compounds was performed along with the prediction of activity spectra for substances (PASS training set. Experimental studies based on antimicrobial activities verified the predictions obtained by the PASS software. Protected rhamnopyranosides 5 and 6 exhibited slight distortion from regular 1C4 conformation, probably due to the fusion of pyranose and isopropylidene ring. Synthesized rhamnopyranosides 4–8 were employed as test chemicals for in vitro antimicrobial evaluation against eight human pathogenic bacteria and two fungi. Antimicrobial and SAR study showed that the rhamnopyranosides were prone against fungal organisms as compared to that of the bacterial pathogens. Interestingly, PASS prediction of the rhamnopyranoside derivatives 4–8 were 0.49 < Pa < 0.60 (where Pa is probability ‘to be active’ as antibacterial and 0.65 < Pa < 0.73 as antifungal activities, which showed significant agreement with experimental data, suggesting rhamnopyranoside derivatives 4–8 were more active against pathogenic fungi as compared to human pathogenic bacteria thus, there is a more than 50% chance that the rhamnopyranoside derivative structures 4–8 have not been reported with antimicrobial activity, making it a possible valuable lead compound.

Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives.

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Akihisa, Toshihiro; Takeda, Ayano; Akazawa, Hiroyuki; Kikuchi, Takashi; Yokokawa, Satoru; Ukiya, Motohiko; Fukatsu, Makoto; Watanabe, Kensuke

2012-08-01

Nine cyclic diarylheptanoids, 1-9, including two new compounds, i.e., 9-oxoacerogenin A (8) and 9-O-β-D-glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10-12, and four phenolic compounds, 13-16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D-glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)-acerogenin B (5), were converted to their ether and ester derivatives, 18-24 and 27-33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1-16 and 18-35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2-4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24-61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88-106% of cell viability at 100 μM). In addition, when compounds 1-16 and 18-35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18-22 and 27-31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC(50) 8.1-19.3 μM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC(50) 10.1-18.4 μM). Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Synthesis and in vitro antibacterial activity of N-methylnitrone and nitrovinyl derivatives of some N-substituted 2-chloroindol-3-carboxaldehydes

Energy Technology Data Exchange (ETDEWEB)

Gatti, R.; Cavrini, V.; Roveri, P.; Bianucci, F.; Legnani, P.

1981-02-01

N-methylnitrones and nitrovinyl derivatives from 1-substituted-2-chloroindol-3-carboxaldehydes were synthesized and evaluated for their in vitro antibacterial activity. Some nitrovinyl derivatives displayed good in vitro activity against Gram-positive bacteria; the compound (II e), 1-(o-chlorobenzyl)-2-chloro-3-(2-nitroethenyl)indole, was more active than nitrofurantoin against Staphylococcus aureus and Streptococcus pyogenes. Some structure-activity relationships are discussed.

Synthesis and trypanocidal activity of 7, 2'-dioxygenated isoflavones and oxypropanolamine derivatives

International Nuclear Information System (INIS)

Faria, Terezinha de J.; Silva, Luiz G. Fonseca e; Souza Filho, Jose D. de; Chiari, Egler; Oliveira, Alaide B. de

2005-01-01

7, 2'-Dihydroxyisoflavone was shown to be active against the bloodstream trypomastigote form of Trypanosoma cruzi, the etiologic agent of Chagas' disease. Amphiphilic derivatives of this isoflavone were synthesized aiming to obtain hydrosoluble compounds of potential use as prophylactic agents to be added to blood for transfusion. This isoflavone was obtained by demethylation of 7-hydroxy-2'-methoxyisoflavone that was synthesized via the intermediate deoxybenzoin. Its reaction with epichlorohydrin, followed by aminolysis with diethylamine, afforded the 7-oxypropanolamine which on treatment with methyl iodide gave the corresponding ammonium salt. The 7-hydroxy-2'-methoxyisoflavone was inactive in the in vitro assays, the 7-oxypropanolamine was more active than 7, 2'-dihydroxyisoflavone while the ammonium salt has not eliminated the parasite from the blood besides causing total lysis of the erythrocytes. The simple synthetic procedures described in the present paper can be used to provide gram quantities of 7, 2'-dihydroxyisoflavone and its 7-oxypropanolamine derivative that should be further investigated in in vivo murine models as potential chemotherapeutic agents for treatment of Chagas' disease. (author)

Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

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Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

2013-08-01

Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design, docking, synthesis and anticancer activity of some novel 2-(4-methylbenzenesulphonamidopentanedioic acid amide derivatives

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Satyajit Dutta

2014-08-01

Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid amide derivatives and the basic compound 2-(4-methylphenylsulfon-amidopentanedioic acid have been designed, synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The modified drugs were docked against the protein histone deacetylase the energy value obtained was o-iodoanilide (-10.370504 and m-iodoanilide (-10.218276 of the titled compound. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ova-rian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female Swiss albino mice against Ehrlich Ascites Carcinoma (EAC. Among the synthesized compounds, o-iodoanilide, m-iodoanilide and p-iodoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

Synthesis of New Thiazole Derivatives Bearing A Sulfonamide Moiety Of Expected Anticancer And Radiosensitizing Activities

International Nuclear Information System (INIS)

Mohamed, S.Sh.I.

2012-01-01

In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new pyrano thiazole and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

E. coli-Derived L-Asparaginase Retains Enzymatic and Cytotoxic Activity In Vitro for Canine and Feline Lymphoma after Cold Storage

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Jackie M. Wypij

2013-01-01

Full Text Available Background. L-asparaginase is effective in treating canine and feline lymphoma, however chemotherapy poses a significant financial cost to veterinary clients, limiting therapy for many pets. Single dose vials result in significant drug wastage, and drug shortages limit consistent availability for pets. Hypothesis. E. coli-derived asparaginase retains enzymatic and antineoplastic activity in canine and feline lymphoma cells after cold storage. Methods. E. coli-derived asparaginase was cold-stored: refrigeration (7–14 days and freezing (14 days–six months, one to three freeze/thaw cycles. Enzymatic activity of asparaginase was measured via a modified asparagine assay. Effects of cold-stored asparaginase on cell proliferation and cytotoxicity were measured in feline (MYA-1, F1B and canine (17–71, OSW lymphoma cells. Results. Cold-stored E. coli-derived asparaginase retains antineoplastic activity in all four cell lines tested. Cold-stored E. coli-derived L-asparaginase depletes asparagine and retains enzymatic activity. Duration of refrigeration, duration of freezing, and number of freeze-thaw cycles have minimal effect on asparaginase enzyme activity. Conclusions and Clinical Importance. This study establishes a scientific basis for long-term cold storage of reconstituted E. coli-derived asparaginase that may result in better utilization of limited drug resources and improve financial feasibility of E. coli-derived asparaginase as a therapeutic option for pets with lymphoma.

Evaluation of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh in a porcine model of ventral hernia repair.

Science.gov (United States)

Scott, Jeffrey R; Deeken, Corey R; Martindale, Robert G; Rosen, Michael J

2016-09-01

The objective of this study was to evaluate the mechanical and histological properties of a fully absorbable poly-4-hydroxybutyrate/absorbable barrier composite mesh (Phasix™ ST) compared to partially absorbable (Ventralight™ ST), fully absorbable (Phasix™), and biologically derived (Strattice™) meshes in a porcine model of ventral hernia repair. Bilateral abdominal surgical defects were created in twenty-four Yucatan pigs, repaired with intraperitoneal (Phasix™ ST, Ventralight™ ST) or retromuscular (Phasix™, Strattice™) mesh, and evaluated at 12 and 24 weeks (n = 6 mesh/group/time point). Prior to implantation, Strattice™ demonstrated significantly higher (p weeks, mesh/repair strength was significantly greater than NAW (p weeks (p > 0.05). Phasix™ mesh/repair strength was significantly greater than Strattice™ (p weeks, and Ventralight™ ST mesh/repair strength was significantly greater than Phasix™ ST mesh (p weeks. At 12 and 24 weeks, Phasix™ ST and Ventralight™ ST were associated with mild inflammation and minimal-mild fibrosis/neovascularization, with no significant differences between groups. At both time points, Phasix™ was associated with minimal-mild inflammation/fibrosis and mild neovascularization. Strattice™ was associated with minimal inflammation/fibrosis, with minimal neovascularization at 12 weeks, which increased to mild by 24 weeks. Strattice™ exhibited significantly less neovascularization than Phasix™ at 12 weeks and significantly greater inflammation at 24 weeks due to remodeling. Phasix™ ST demonstrated mechanical and histological properties comparable to partially absorbable (Ventralight™ ST) and fully resorbable (Phasix™) meshes at 12 and 24 weeks in this model. Data also suggest that fully absorbable meshes with longer-term resorption profiles may provide improved mechanical and histological properties compared to biologically derived scaffolds.

In vitro activities of novel 4-HPR derivatives on a panel of rhabdoid and other tumor cell lines

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Das Bhaskar C

2011-09-01

Full Text Available Abstract Background Rhabdoid tumors (RTs are aggressive pediatric malignancies with poor prognosis. N-(4-hydroxy phenyl retinamide (4-HPR or fenretinide is a potential chemotherapeutic for RTs with activity correlated to its ability to down-modulate Cyclin D1. Previously, we synthesized novel halogen-substituted and peptidomimetic-derivatives of 4-HPR that retained activity in MON RT cells. Here we analyzed the effect of 4-HPR in inhibiting the growth of several RT, glioma, and breast cancer cell lines and tested their effect on cell cycle, apoptosis and Cyclin D1 expression. Methods Effect of compounds on RT cell cycle profiles, and cell death were assessed by MTS cell survival assays and FACS analysis. The effects of treatment on Cyclin D1 expression were determined by immunoblotting. The efficacy of these compounds on glioma and breast cancer cell lines was also determined using MTS assays. Results Low micromolar concentrations of 4-HPR derivatives inhibited cell survival of all RT cells tested. The 4-HPR derivatives altered RT cell cycle profiles and induced high levels of cell death that was correlated with their potency. ATRA exhibited high IC50 values in all cell lines tested and did not cause cell death. In MON RT cells, the iodo-substituted compounds were more active than 4-HPR in inducing cell cycle arrest and apoptosis. Additionally, the activity of the compounds correlated with their ability to down-modulate Cyclin D1: while active compounds reduced Cyclin D1 levels, inactive ATRA did not. In glioma and breast cancer cell lines, 4-HPR and 4-HPR derivatives showed variable efficacy. Conclusions Here we demonstrate, for the first time, that the inhibitory activities of novel halogen-substituted and peptidomimetic derivatives of 4-HPR are correlated to their ability to induce cell death and down-modulate Cyclin D1. These 4-HPR derivatives showed varied potencies in breast cancer and glioma cell lines. These data indicate that further

High performance supercapacitor from activated carbon derived from waste orange skin

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Ahmed, Sultan; Hussain, S.; Ahmed, Ahsan; Rafat, M.

2018-05-01

Activated carbon due to its inherent properties such as large surface area and low cost is most frequently used electrode material for supercapacitor. Activated carbon has been previously derived from various biomass such as coconut shell, coffee bean etc. Herein, we report the synthesis of activated carbon from waste orange skin. The material was synthesized employing chemical activation method and the success of synthesis was confirmed by its physical and electrochemical properties. The physical properties of the as-prepared sample were studied using the techniques of XRD, SEM, Raman spectroscopy and N2 adsorption/desorption analysis while its electrochemical properties were studied in two-electrode assembly using liquid electrolyte (consisting of 1 M solution of LiTFSI dispersed in ionic liquid EMITFSI) and employing the techniques of cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge- discharge. The synthesized sample of activated carbon exhibits high specific capacitance of 115 F g-1 at 10 mV s-1. Also, the activated carbon electrode shows the retention of ˜75% in initial capacitance value for more than 2000 initial cycles, indicating the as-prepared activated carbon can be profitably used as electrode material for energy storage devices.

Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles

Science.gov (United States)

Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

2015-01-01

Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

CMS on the GRID: Toward a fully distributed computing architecture

International Nuclear Information System (INIS)

Innocente, Vincenzo

2003-01-01

The computing systems required to collect, analyse and store the physics data at LHC would need to be distributed and global in scope. CMS is actively involved in several grid-related projects to develop and deploy a fully distributed computing architecture. We present here recent developments of tools for automating job submission and for serving data to remote analysis stations. Plans for further test and deployment of a production grid are also described

C{sub 60}-based ebselen derivative: synthesis by bingel cyclopropanation and enhanced antioxidative and neuroprotective activity

Energy Technology Data Exchange (ETDEWEB)

Xufeng Liu [HuaZhong University of Science and Technology, Wuhan (China). Dept. of Chemistry; Wenchao Guan [Ministry of Education, Wuhan, (China). Hubei University. Key Lab. for the Synthesis and Application of Organic Functional Molecules]. E-mail: wcguan04@yahoo.com.cn; Wengshan Ke [Hubei University, Wuhan (China). College of Life Science

2007-07-01

C{sub 60}-based ebselen derivative 3 was synthesized through Bingel cyclopropanation of C{sub 60} with the ebselen malonate 2. Compound 3 was obtained in 42% yield (based on consumed C{sub 60}) in a three-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2aminoethoxy)ethanol. Its structure was confirmed by {sup 1H} NMR, {sup 13}C NMR, IR, UV and FAB-MS spectroscopy analyses. In order to verify the enhanced antioxidative and neuroprotective activity of 3, a C{sub 60} derivative (4), an ebselen derivative (2), and their mixture (4 plus 2 in equimolar ratio) were employed to treat cortical neuronal cells, following the same procedure used with 3 and at the same final concentration (30 {mu}mol L{sup -1}). Cell viabilities of the four treated groups were estimated by LDH (lactic dehydrogenase) leakage and MTT (3-(4, 5-dimethylthiazole-2yl)-2,5-diphenyl-tetrazolium bromide) assays. Results showed that the antioxidative and protective activities of C{sub 60}-based ebselen derivative 3 against H{sub 2}O{sub 2}-mediated neuronal injury (MTT(OD) 0.364 {+-} 0.028; LDH release (UL{sup -1}) 4.66 {+-} 0.28) were significantly higher than those of C{sub 6})0 derivative 4 (MTT(OD) 0.324 {+-} 0.025; LDH release (UL{sup -1}) 5.39 {+-} 0.17), ebselen derivative 2 (MTT(OD) 0.294 {+-} 0.021; LDH release (UL{sup -1}) 5.71 {+-} 0.27), and the mixture of 4 and 2 (MTT(OD) 0.310 {+-} 0.018; LDH release (UL{sup -1}) 5.54 {+-}0.39). These findings demonstrated that the combination of two molecular units with similar biological activities (C{sub 60} and ebselen) may be a desirable way of obtaining new and more biologically effective C{sub 60}-based compounds. (author)

Structure Activity Relationship of Brevenal Hydrazide Derivatives

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Allan Goodman

2014-03-01

Full Text Available Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and bronchoconstriction. Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial attributes when administered alone. For example, in an asthmatic sheep model, brevenal has been shown to increase tracheal mucosal velocity, an attribute which has led to its development as a potential treatment for Cystic Fibrosis. The mechanism of action of brevenal is poorly understood and the exact binding site has not been elucidated. In an attempt to further understand the mechanism of action of brevenal and potentially develop a second generation drug candidate, a series of brevenal derivatives were prepared through modification of the aldehyde moiety. These derivatives include aliphatic, aromatic and heteroaromatic hydrazide derivatives. The brevenal derivatives were tested using in vitro synaptosome binding assays to determine the ability of the compounds to displace brevetoxin and brevenal from their native receptors. A sheep inhalation model was used to determine if instillation of the brevenal derivatives resulted in bronchoconstriction. Only small modifications were tolerated, with larger moieties leading to loss of affinity for the brevenal receptor and bronchoconstriction in the sheep model.

Novel derivatives of 6-mercaptopurine: synthesis, characterization and antiproliferative activities of S-allylthio-mercaptopurines.

Science.gov (United States)

Miron, T; Arditti, F; Konstantinovski, L; Rabinkov, A; Mirelman, D; Berrebi, A; Wilchek, M

2009-02-01

Biologically active S-allylthio derivatives of 6-mercaptopurine (6-MP) and 6-mercaptopurine riboside (6-MPR) were synthesized. The products, S-allylthio-6-mercaptopurine (SA-6MP) and S-allylthio-6-mercaptopurine riboside (SA-6MPR) were characterized. The antiproliferative activity of the new prodrugs was tested on human leukemia and monolayer cell lines, and compared to that of their parent reactants. The new prodrugs acted by a concentration-dependent mechanism. They inhibited cell proliferation and induced-apoptosis more efficiently than the parent molecules. Leukemia cell lines were more sensitive to the new prodrugs than monolayer cell lines. Higher hydrophobicity of the derivatives improves their penetration into cells, where upon reaction with glutathione, S-allylthioglutathione (GSSA) is formed, and 6-MP or 6-MPR is released for further processing.

Synthesis and in-vitro antibacterial activity of N-piperazinyl quinolone derivatives with 5-chloro-2-thienyl group

Directory of Open Access Journals (Sweden)

2008-08-01

Full Text Available Background and the purpose of the study: Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases. The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity. Methods: Reaction of ciprofloxacin (1, norfloxacin (2 and enoxacin (3 with α-bromoketone 10 or α-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO3 at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7(a-c, respectively. Results and major conclusion: The synthesized compounds were tested against a series of Gram-positive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives (compounds 4a, 5a, 6a and 7a were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-(5-chlorothiophen-2-yl-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 μg/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug (ciprofloxacin against all Gram-positive bacteria with the exception of E. feacalis.

Antifungal activity of tioconazole (UK-20,349), a new imidazole derivative.

Science.gov (United States)

Jevons, S; Gymer, G E; Brammer, K W; Cox, D A; Leeming, M R

1979-04-01

Tioconazole (UK-20,349), a new antifungal imidazole derivative, was compared with miconazole for activity in vitro against Candida spp., Torulopsis glabrata, Cryptococcus neoformans, Aspergillus spp., and dermatophyte fungi (Trichophyton spp. and Microsporum spp.). Tioconazole was more active than miconazole against all the fungal species examined except Aspergillus, against which both agents showed similar activity. Both tioconazole and miconazole inhibited the growth of all fungi examined at concentrations well below their quoted minimum inhibitory concentrations. Their activity against fungi in vivo was investigated in mice infected systemically with Candida albicans. Both agents significantly reduced the numbers of viable Candida cells recoverable from the kidneys of infected animals, with tioconazole producing a generally more marked reduction. After administration of a single oral dose (25 mg/kg) to beagle dogs or white mice, higher and more sustained circulating levels of bioactive drug were detectable of tioconazole than of miconazole. These observations suggest that tioconazole may have potential in the treatment of both superficial and systemic mycoses in humans.

A Multi-Scale Flood Monitoring System Based on Fully Automatic MODIS and TerraSAR-X Processing Chains

Directory of Open Access Journals (Sweden)

Enrico Stein

2013-10-01

Full Text Available A two-component fully automated flood monitoring system is described and evaluated. This is a result of combining two individual flood services that are currently under development at DLR’s (German Aerospace Center Center for Satellite based Crisis Information (ZKI to rapidly support disaster management activities. A first-phase monitoring component of the system systematically detects potential flood events on a continental scale using daily-acquired medium spatial resolution optical data from the Moderate Resolution Imaging Spectroradiometer (MODIS. A threshold set controls the activation of the second-phase crisis component of the system, which derives flood information at higher spatial detail using a Synthetic Aperture Radar (SAR based satellite mission (TerraSAR-X. The proposed activation procedure finds use in the identification of flood situations in different spatial resolutions and in the time-critical and on demand programming of SAR satellite acquisitions at an early stage of an evolving flood situation. The automated processing chains of the MODIS (MFS and the TerraSAR-X Flood Service (TFS include data pre-processing, the computation and adaptation of global auxiliary data, thematic classification, and the subsequent dissemination of flood maps using an interactive web-client. The system is operationally demonstrated and evaluated via the monitoring two recent flood events in Russia 2013 and Albania/Montenegro 2013.

Proportional Derivative Active Force Control for “X” Configuration Quadcopter

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Niam Tamami

2014-12-01

Full Text Available This paper present a control method “x” configuration quadcopter. The control method used PDAFC (Proportional Derivative Active Force Control. PD is used to stabilize quadcopter, and AFC is used to reject uncertainty disturbance (e.g. wind by estimate disturbance torque value of quadcopter. By adding PD with AFC, better result is obtained, AFC can minimize uncertainty disturbance effect. The sensitivity toward uncertainty disturbance can be set from sensitivity constant to get best performance of disturbance rejection. Stability analysis of PDAFC was evaluated by Lyapunov stability theory.

Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

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Yang, Yifei; Zhang, Yuan; Yang, LingYun; Zhao, Leilei; Si, Lianghui; Zhang, Huibin; Liu, Qingsong; Zhou, Jinpei

2017-02-01

Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC 50 of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment. Copyright © 2016. Published by Elsevier Inc.

New approach to solve symmetric fully fuzzy linear systems

Indian Academy of Sciences (India)

concepts of fuzzy set theory and then define a fully fuzzy linear system of equations. .... To represent the above problem as fully fuzzy linear system, we represent x .... Fully fuzzy linear systems can be solved by Linear programming approach, ...

Synthesis of fully and partially sulfonated polyanilines derived from ortanilic acid: An electrochemical and electromicrogravimetric study

International Nuclear Information System (INIS)

Cano Marquez, Abraham Guadalupe; Torres Rodriguez, Luz Maria; Montes Rojas, Antonio

2007-01-01

The electrochemical polymerization of 2-aminobenzene sulfonic acid, also called ortanilic acid (o-ASA), on a gold electrode precoated with polyaniline (PANI), has been carried out. We proved that the electropolymerization of o-ASA is enhanced on PANI electrodes, resulting in thicker films obtained in aqueous media at room temperature. The electrosynthesized film (P(o-ASA)) was characterized by cyclic voltammetry, FTIR and nuclear magnetic resonance. The compensation of P(o-ASA) charge was evaluated using electrochemical quartz crystal microbalance combined with cyclic voltammetry, which showed that the electroneutralization process mainly involves cations. Additionally, copolymers of aniline and o-ASA were electrosynthesized, using a metallic electrode modified with PANI also as a working electrode. The degree of sulfanation of copolymers has been modulated with the proportions of monomers in the electrosynthesis solution. The studies reveal a more important participation of cations in fully sulfonated polyaniline than in partially sulfonated polyaniline

How a Fully Automated eHealth Program Simulates Three Therapeutic Processes: A Case Study.

Science.gov (United States)

Holter, Marianne T S; Johansen, Ayna; Brendryen, Håvar

2016-06-28

eHealth programs may be better understood by breaking down the components of one particular program and discussing its potential for interactivity and tailoring in regard to concepts from face-to-face counseling. In the search for the efficacious elements within eHealth programs, it is important to understand how a program using lapse management may simultaneously support working alliance, internalization of motivation, and behavior maintenance. These processes have been applied to fully automated eHealth programs individually. However, given their significance in face-to-face counseling, it may be important to simulate the processes simultaneously in interactive, tailored programs. We propose a theoretical model for how fully automated behavior change eHealth programs may be more effective by simulating a therapist's support of a working alliance, internalization of motivation, and managing lapses. We show how the model is derived from theory and its application to Endre, a fully automated smoking cessation program that engages the user in several "counseling sessions" about quitting. A descriptive case study based on tools from the intervention mapping protocol shows how each therapeutic process is simulated. The program supports the user's working alliance through alliance factors, the nonembodied relational agent Endre and computerized motivational interviewing. Computerized motivational interviewing also supports internalized motivation to quit, whereas a lapse management component responds to lapses. The description operationalizes working alliance, internalization of motivation, and managing lapses, in terms of eHealth support of smoking cessation. A program may simulate working alliance, internalization of motivation, and lapse management through interactivity and individual tailoring, potentially making fully automated eHealth behavior change programs more effective.

Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities.

Science.gov (United States)

Mohamad, Saharuddin Bin; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

2002-01-01

Gc protein has been reported to be a precursor of Gc protein-derived macrophage activation factor (GcMAF) in the inflammation-primed macrophage activation cascade. An inducible beta-galactosidase of B cells and neuraminidase of T cells convert Gc protein to GcMAF. Gc protein from human serum was purified using 25(OH)D3 affinity column chromatography and modified to GcMAF using immobilized glycosidases (beta-galactosidase and neuraminidase) The sugar moiety structure of GcMAF was characterized by lectin blotting by Helix pomatia agglutinin. The biological activities of GcMAF were evaluated by a superoxide generation assay and a phagocytosis assay. We successfully purified Gc protein from human serum. GcMAF was detected by lectin blotting and showed a high biological activity. Our results support the importance of the terminal N-acetylgalactosamine moiety in the GcMAF-mediated macrophage activation cascade, and the existence of constitutive GcMAF in human serum. These preliminary data are important for designing small molecular GcMAF mimics.

Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

Directory of Open Access Journals (Sweden)

Mervi Alanne-Kinnunen

Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

Synthesis and antiproliferative activity of novel limonene derivatives with a substituted thiourea moiety

International Nuclear Information System (INIS)

Figueiredo, Isis M.; Santos, Luciane V. dos; Costa, Willian F. da; Silva, Cleuza C. da; Sarragiotto, Maria H.; Carvalho, Joao E. de; Sacoman, Juliana L.; Kohn, Luciana K.

2006-01-01

A series of R-(+)-limonene derivatives bearing a substituted thiourea moiety (3-13) and five S-methyl analogs (14-18) were synthesized and evaluated for their in vitro antiproliferative activity against human cancer cell lines. Compounds bearing aromatic substituents (3-6) exhibit cytostatic activity in the full panel of cell lines tested, with GI 50 values in the range of 2.5 to 24 μmol L -1 . Compounds 3, 10, 12 and 16 were the most active with GI 5 )0 values in the range of 0.41 to 3.0 μmol L -1 , against different cell lines. (author)

Synthesis and antileishmanial activity of new 1-Aryl-1H-Pyrazole-4- carboximidamides derivatives

Energy Technology Data Exchange (ETDEWEB)

Santos, Mauricio S. dos; Gomes, Adriana O.; Bernardino, Alice M.R.; Souza, Marcos C. de, E-mail: alicerolim@globo.co [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Programa de Pos-Graduacao em Quimica Organica; Khan, Misbahul A. [The Islamia University of Bahawalpur (Pakistan). Chemistry Dept.; Brito, Monique A. de [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Fac. de Farmacia. Lab. de Quimica Medicinal Computacional; Castro, Helena C.; Abreu, Paula A. [Universidade Federal Fluminense (LABioMol/GCM/UFF), Niteroi, RJ (Brazil). Inst. de Biologia. Lab. de Antibioticos, Bioquimica e Modelagem Molecular; Rodrigues, Carlos R. [Universidade Federal do Rio de Janeiro (ModMol/UFRJ), RJ (Brazil). Fac. de Farmacia. Lab. de Modelagem Molecular e QSAR; Leo, Rosa M.M. de; Leon, Leonor L.; Canto-Cavalheiro, Marilene M. [Fundacao Oswaldo Cruz (IOC/FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto Oswaldo Cruz. Lab. de Bioquimica de Tripanosomatideos

2011-07-01

Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies. (author)

Antiadherent and Antibiofilm Activity of Humulus lupulus L. Derived Products: New Pharmacological Properties

Directory of Open Access Journals (Sweden)

Marcin Rozalski

2013-01-01

Full Text Available New antimicrobial properties of products derived from Humulus lupulus L. such as antiadherent and antibiofilm activities were evaluated. The growth of gram-positive but not gram-negative bacteria was inhibited to different extents by these compounds. An extract of hop cones containing 51% xanthohumol was slightly less active against S. aureus strains (MIC range 31.2–125.0 μg/mL than pure xanthohumol (MIC range 15.6–62.5 μg/mL. The spent hop extract, free of xanthohumol, exhibited lower but still relevant activity (MIC range 1-2 mg/mL. There were positive coactions of hop cone, spent hop extracts, and xanthohumol with oxacillin against MSSA and with linezolid against MSSA and MRSA. Plant compounds in the culture medium at sub-MIC concentrations decreased the adhesion of Staphylococci to abiotic surfaces, which in turn caused inhibition of biofilm formation. The rate of mature biofilm eradication by these products was significant. The spent hop extract at MIC reduced biofilm viability by 42.8%, the hop cone extract by 74.8%, and pure xanthohumol by 86.5%. When the hop cone extract or xanthohumol concentration was increased, almost complete biofilm eradication was achieved (97–99%. This study reveals the potent antibiofilm activity of hop-derived compounds for the first time.

Exact closed-form solutions of a fully nonlinear asymptotic two-fluid model

Science.gov (United States)

Cheviakov, Alexei F.

2018-05-01

A fully nonlinear model of Choi and Camassa (1999) describing one-dimensional incompressible dynamics of two non-mixing fluids in a horizontal channel, under a shallow water approximation, is considered. An equivalence transformation is presented, leading to a special dimensionless form of the system, involving a single dimensionless constant physical parameter, as opposed to five parameters present in the original model. A first-order dimensionless ordinary differential equation describing traveling wave solutions is analyzed. Several multi-parameter families of physically meaningful exact closed-form solutions of the two-fluid model are derived, corresponding to periodic, solitary, and kink-type bidirectional traveling waves; specific examples are given, and properties of the exact solutions are analyzed.

Free vibration of fully functionally graded carbon nanotube reinforced graphite/epoxy laminates

Science.gov (United States)

Kuo, Shih-Yao

2018-03-01

This study provides the first-known vibration analysis of fully functionally graded carbon nanotube reinforced hybrid composite (FFG-CNTRHC) laminates. CNTs are non-uniformly distributed to reinforce the graphite/epoxy laminates. Some CNT distribution functions in the plane and thickness directions are proposed to more efficiently increase the stiffening effect. The rule of mixtures is modified by considering the non-homogeneous material properties of FFG-CNTRHC laminates. The formulation of the location dependent stiffness matrix and mass matrix is derived. The effects of CNT volume fraction and distribution on the natural frequencies of FFG-CNTRHC laminates are discussed. The results reveal that the FFG layout may significantly increase the natural frequencies of FFG-CNTRHC laminate.

Improving oocyte quality by transfer of autologous mitochondria from fully grown oocytes

DEFF Research Database (Denmark)

Kristensen, Stine Gry; Pors, Susanne Elisabeth; Andersen, Claus Yding

2017-01-01

options using autologous mitochondria to potentially augment pregnancy potential in ART. Autologous transfer of mitochondria from the patient's own germline cells has attracted much attention as a possible new treatment to revitalize deficient oocytes. IVF births have been reported after transfer...... of oogonial precursor cell-derived mitochondria; however, the source and quality of the mitochondria are still unclear. In contrast, fully grown oocytes are loaded with mitochondria which have passed the genetic bottleneck and are likely to be of high quality. An increased supply of such oocytes could...... with high quality mitochondria can be obtained from natural or stimulated ovaries and potentially be used to improve both quality and quantity of oocytes available for fertility treatment....

Probing the Active Surface Sites for CO Reduction on Oxide-Derived Copper Electrocatalysts

DEFF Research Database (Denmark)

Verdaguer Casadevall, Arnau; Li, Christina W.; Johansson, Tobias Peter

2015-01-01

CO electroreduction activity on oxide-derived Cu (OD-Cu) was found to correlate with metastable surface features that bind CO strongly. OD-Cu electrodes prepared by H-2 reduction of Cu2O precursors reduce CO to acetate and ethanol with nearly 50% Faradaic efficiency at moderate overpotential. Tem...

Cooperative study of clinical benefits from use of the fully portable blood irradiator

International Nuclear Information System (INIS)

Hungate, F.P.

1994-10-01

This report looks at the clinical benefits from use of a fully portable blood irradiator, techniques developed by Pacific Northwest Laboratory. Significant accomplishments included the following: blood irradiators were successfully fabricated by PNL; irradiators were activated at the University of Missouri and quality tested at PNL; A-V shunts for irradiators were successfully fabricated in the PNL plastics shop; all activities necessary for experimental work on animals using the blood irradiators were completed

Cooperative study of clinical benefits from use of the fully portable blood irradiator

Energy Technology Data Exchange (ETDEWEB)

Hungate, F.P.

1994-10-01

This report looks at the clinical benefits from use of a fully portable blood irradiator, techniques developed by Pacific Northwest Laboratory. Significant accomplishments included the following: blood irradiators were successfully fabricated by PNL; irradiators were activated at the University of Missouri and quality tested at PNL; A-V shunts for irradiators were successfully fabricated in the PNL plastics shop; all activities necessary for experimental work on animals using the blood irradiators were completed.

Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

Directory of Open Access Journals (Sweden)

Bekdemir Yunus

2008-08-01

Full Text Available Abstract Background Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance. Methods Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested. Results The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably. Conclusion This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.

Synthesis and Larvicidal and Adult Topical Activity of Some Hydrazide-Hydrazone Derivatives Against Aedes aegypti

Science.gov (United States)

2014-01-01

anticancer, antifungal, antiviral, antitumoral, antibacterial and antimalarial activities [11-13]. Recently, our group has been investigating the...ABSTRACT A series of novel hydrazide-hydrazone derivatives were synthesized and evaluated for their larvicidal and adult topical activity against...4b) showed noteworthy larvacidal activity against Aedes aegypti. Dose-response data of compound 4b showed LC50 and LC90 values of 30.5 (15.4 – 22.7

Design and synthesis of novel C14-urea-tetrandrine derivatives with potent anti-cancer activity.

Science.gov (United States)

Lan, Junjie; Huang, Lan; Lou, Huayong; Chen, Chao; Liu, Tangjingjun; Hu, Shengcao; Yao, Yao; Song, Junrong; Luo, Jun; Liu, Yazhou; Xia, Bin; Xia, Lei; Zeng, Xueyi; Ben-David, Yaacov; Pan, Weidong

2018-01-01

Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9). Compound 4g showed strongest cytotoxic effect against PC3 cells with IC 50 value of 0.64 μM, which was 12-fold, 31-fold and 26-fold lower than the parental tetrandrine, 5-fluorouracil and cisplatin, respectively. Preliminary structure-activity relationship study indicated that urea subsititution was the key pharmacophore for the enhancement of their antitumor activities. Induction of apoprosis by 4g was associated with the activation of pro-apoptotic protein BAX and inhibition of antiapoptosis proteins survivin as well as Bcl-2. Moreover, activation of caspases led to increase cleavage of PARP, which further accelerates apoptotic cell death. These results reveal that the compound 4g may be used as a potential anticancer drug candidate. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Quantitative Structure-Activity Relationships (QSAR Study of Piperine Based Derivatives with Leishmanicidal Activity

Directory of Open Access Journals (Sweden)

Edilson Beserra Alencar Filho

2017-04-01

Full Text Available Leishmaniasis is a parasitic disease which represents a serious public health problem in developing countries. It is considered a neglected tropical disease, for which there is little initiative in the search for therapeutic alternatives by pharmaceutical industry. Natural products remain a great source of inspiration for obtaining bioactive molecules. In 2010, Singh and co-workers published the synthesis and in vitro biological activity of piperoyl-aminoacid conjugates, as well as of piperine, against cellular cultures of Leishmania donovani. The piperine is an alkaloid isolated from Piper nigrum that has many activities described in the literature. In this work, we present a Quantitative Structure-Activity Study of piperine derivatives tested by Singh and co-workers, aiming to highlight important molecular features for leishmanicidal activity, obtaining a mathematical model to predict the activity of new analogs. Compounds were submitted to a geometry optimization computational procedure at semiempirical level of quantum theory. Molecular descriptors for the set of compounds were calculated by E-Dragon online plataform, followed by a variable selection procedure using Ordered Predictors Selection algorithm. Validation parameters obtained showed that a good QSAR model, based on multiple linear regression, was obtained (R2 = 0.85; Q2 = 0.69, and the following conclusions regarding the structure-activity relationship were elucidated: Compounds with electronegative atoms on different substituent groups of analogs, absence of unsaturation on lateral chain, presence of ester instead of carboxyl, and large volumes (due the presence of additional aromatic rings trends to increase the activity against promastigote forms of leishmania. DOI: http://dx.doi.org/10.17807/orbital.v9i1.893

4-Aminoquinoline derivatives

DEFF Research Database (Denmark)

Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum

2016-01-01

and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei......Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives...... for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax....

Efficient, long term production of monocyte-derived macrophages from human pluripotent stem cells under partly-defined and fully-defined conditions.

Directory of Open Access Journals (Sweden)

Bonnie van Wilgenburg

Full Text Available Human macrophages are specialised hosts for HIV-1, dengue virus, Leishmania and Mycobacterium tuberculosis. Yet macrophage research is hampered by lack of appropriate cell models for modelling infection by these human pathogens, because available myeloid cell lines are, by definition, not terminally differentiated like tissue macrophages. We describe here a method for deriving monocytes and macrophages from human Pluripotent Stem Cells which improves on previously published protocols in that it uses entirely defined, feeder- and serum-free culture conditions and produces very consistent, pure, high yields across both human Embryonic Stem Cell (hESC and multiple human induced Pluripotent Stem Cell (hiPSC lines over time periods of up to one year. Cumulatively, up to ∼3×10(7 monocytes can be harvested per 6-well plate. The monocytes produced are most closely similar to the major blood monocyte (CD14(+, CD16(low, CD163(+. Differentiation with M-CSF produces macrophages that are highly phagocytic, HIV-1-infectable, and upon activation produce a pro-inflammatory cytokine profile similar to blood monocyte-derived macrophages. Macrophages are notoriously hard to genetically manipulate, as they recognise foreign nucleic acids; the lentivector system described here overcomes this, as pluripotent stem cells can be relatively simply genetically manipulated for efficient transgene expression in the differentiated cells, surmounting issues of transgene silencing. Overall, the method we describe here is an efficient, effective, scalable system for the reproducible production and genetic modification of human macrophages, facilitating the interrogation of human macrophage biology.

Deterrent activity of hops flavonoids and their derivatives against stored product pests.

Science.gov (United States)

Jackowski, J; Popłoński, J; Twardowska, K; Magiera-Dulewicz, J; Hurej, M; Huszcza, E

2017-10-01

Five flavonoids from hops, two of their derivatives, along with naringenin used as a model compound, were tested for their antifeedant activity against three coleopteran stored product pests: Sitophilus granarius L., Tribolium confusum Duv. and Trogoderma granarium Everts. The introduction, into the tested flavonoid molecules, of additional structural fragments such as prenyl or dimethylpyran moiety, is proposed to significantly alter the deterrent activity of the compounds. The prenyl moiety in flavonoids increased the deterrent activity of these compounds in all three of the grain feeding species used in the tests. It is also concluded that the introduction of dimethylpyran moiety to the flavonoid structure increases its deterrent activity in S. granarius and T. confusum, but in one of the test insects, T. granarium, an increased feeding was observed in response to the introduction of dimethylpyran moiety to the flavonoid structure.

Fully integrated biochip platforms for advanced healthcare.

Science.gov (United States)

Carrara, Sandro; Ghoreishizadeh, Sara; Olivo, Jacopo; Taurino, Irene; Baj-Rossi, Camilla; Cavallini, Andrea; de Beeck, Maaike Op; Dehollain, Catherine; Burleson, Wayne; Moussy, Francis Gabriel; Guiseppi-Elie, Anthony; De Micheli, Giovanni

2012-01-01

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.

Design, synthesis and antifungal activities of novel strobilurin derivatives containing pyrimidine moieties

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiang; Geo, Yongxin; Liu, Huijun; Guo, Baoyuan; Wang, Huili [Research Center for Eco-Environmental Sciences/Chinese Academy of Sciences, Beijing (China)

2012-04-15

Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β-methoxy acrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, {sup 1}H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds (1a-1h) exhibited potent antifungal activities against Colletotrichum orbicular, Botrytis cinerea Pers and Protoporphyria caps ici Leon ian at the concentration of 50 μg/mL. Exhilaratingly, compound 1d (R=3-trifluoromethylphenyl) showed better antifungal activity against all the tested fungi than the commercial stilbenetriol fungicide azoxystrobin.

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

Energy Technology Data Exchange (ETDEWEB)

Pacheco, Dency J.; Trilleras, Jorge; Prent, Luis; Coaves, Tobinson [Universidad del Atlantico, Barranquilla-Atlantico (Colombia). Facultad de Ciencias Basicas. Grupo de Investigacion en Compuestos Heterociclicos; Quiroga, Jairo [Universidad del Valle, Cali (Colombia). Dept. de Quimica. Grupo de Investigacion de Compuestos Heterociclicos; Gutierrez, Jennifer; Delgado, Gabriela [Universidad Nacional de Colombia, Bogota, D.C. (Colombia). Facultad de Ciencias. Departamento de Farmacia. Grupo de Investigacion en Inmunotoxicologia; Marin, Juan C. [Universidad Nacional de Colombia, Bogota, D.C. (Colombia). Facultad de Ciencias. Departamento de Farmacia. Grupo de Investigacion Farmacognosia y Fitoquimica

2013-10-15

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{sub 50} EC{sub 50} {sup -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)

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)

Imbalances in Mobilization and Activation of Pro-Inflammatory and Vascular Reparative Bone Marrow-Derived Cells in Diabetic Retinopathy.

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Harshini Chakravarthy

Full Text Available Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs. We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BM-derived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

Anti-angiogenic activity of a new andrographolide derivative in zebrafish and HUVECs.

Science.gov (United States)

Li, Jingjing; Peng, Yuran; Li, Shang; Sun, Yicheng; Chan, Judy Yuet-Wa; Cui, Guozhen; Wang, Decai; Zhou, Guo-Chun; Lee, Simon Ming-Yuen

2016-10-15

Andrographolide is among the most promising anti-tumor and anti-angiogenic components in Andrographis paniculata but its poor bioavailability and limited efficacy pose difficulties for its therapeutic development. Therefore, improving its pharmaceutical features and potency, by modifying its chemical structure, is desirable. In the present study, a new andrographolide derivative (AGP-40) was synthesized and characterized for its anti-angiogenic properties. Human umbilical vein endothelial cells (HUVECs) and zebrafish models were used to identify the anti-angiogenic activity of AGP-40. AGP-40 significantly suppressed the formation of blood vessels in zebrafish and inhibited proliferation, migration and tube formation in vitro. The anti-angiogenic effects of AGP-40 are at least partially mediated via the PI3K/Akt and MEK/Erk(1/2) signaling pathways. Furthermore, AGP-40 exhibited stronger anti-proliferative effects than andrographolide against A549, HepG2, Hela cancer cell lines. This study is the first to demonstrate the promising anti-angiogenic activity of the new andrographolide derivative AGP-40. Our results indicate that AGP-40 could serve as a potential therapeutic agent for the treatment and prevention of diseases associated with excessive angiogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Tannins and Tannin-Related Derivatives Enhance the (Pseudo-)Halogenating Activity of Lactoperoxidase.

Science.gov (United States)

Gau, Jana; Prévost, Martine; Van Antwerpen, Pierre; Sarosi, Menyhárt-Botond; Rodewald, Steffen; Arnhold, Jürgen; Flemmig, Jörg

2017-05-26

Several hydrolyzable tannins, proanthocyanidins, tannin derivatives, and a tannin-rich plant extract of tormentil rhizome were tested for their potential to regenerate the (pseudo-)halogenating activity, i.e., the oxidation of SCN - to hypothiocyanite - OSCN, of lactoperoxidase (LPO) after hydrogen peroxide-mediated enzyme inactivation. Measurements were performed using 5-thio-2-nitrobenzoic acid in the presence of tannins and related substances in order to determine kinetic parameters and to trace the LPO-mediated - OSCN formation. The results were combined with docking studies and molecular orbital analysis. The - OSCN-regenerating effect of tannin derivatives relates well with their binding properties toward LPO as well as their occupied molecular orbitals. Especially simple compounds like ellagic acid or methyl gallate and the complex plant extract were found as potent enzyme-regenerating compounds. As the (pseudo-)halogenating activity of LPO contributes to the maintenance of oral bacterial homeostasis, the results provide new insights into the antibacterial mode of action of tannins and related compounds. Furthermore, chemical properties of the tested compounds that are important for efficient enzyme-substrate interaction and regeneration of the - OSCN formation by LPO were identified.

Relationship Between Structure and Antiproliferative Activity of Novel 5-amino-4-cyanopyrazole-1-formaldehydehydrazono Derivatives on HL-60RG Human Leukemia Cells.

Science.gov (United States)

Nagahara, Yukitoshi; Nagahara, Katsuhiko

2017-11-01

Pyrazole derivatives have been reported to have potent antimicrobial and anticancer activity. We recently synthesized and determined the effects of analogs, benzamidoxime derivatives, on mammalian cells and discovered that benzamidoximes had an antiproliferative effect. Here we synthesized and determined the anticancer effects of hydrazonopyrazole derivatives on a mammalian cancer cell line. We synthesized 12 hydrazonopyrazole derivatives with several constant alkyl chain length or branched chains at the side chain to investigate their anticancer cell activity, using the human myelogenous leukemia cell line HL-60RG. Among all hydrazonopyrazole derivatives we synthesized, the hydrazonopyrazole derivative with a branched chain at the side chain rather than a constant alkyl chain significantly inhibited cell viability. The strongest hydrazonopyrazole derivative, 5-amino-4-cyanopyrazole-1-formaldehydehydrazono-3'-pentanal, tended to damage cells dose-dependently. This cell growth attenuation was a result of apoptosis, activating caspase-3 and fragmented DNA. Hydrazonopyrazole derivatives induced apoptosis of HL-60RG leukemia cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Hemocyanin-derived phenoloxidase activity is dependent on dodecameric structure in shrimp Litopenaeus vannamei

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Wang Ke-Zhou

2015-01-01

Full Text Available Hemocyanin (Hc is a multifunctional protein in both mollusks and arthropods. Phenoloxidase (PO activities are the most important physiological functions for Hcs after conversion. In shrimp, Hc occurs as two oligomer forms, dodecamers and hexamers. Differences in the transport oxygen capacity and agglutination activity between the two oligomers of shrimp Hc have been found. In the present study, we investigated the differences in the Hc-derived PO activity between the dodecameric and hexameric Hc forms of the shrimp Litopenaeus vannamei. The two oligomers were separated by non-denaturing polyacrylamide gel electrophoresis, converted by trypsin cleavage and their PO activities were determined by oxidation of L-DOPA. The dodecamers exhibited PO activity after enzymatic conversion while the hexamers did not exhibit PO activity. This result provides new insight into the structural/functional relationships of Hcs.

21 CFR 184.1685 - Rennet (animal-derived) and chymosin preparation (fermentation-derived).

Science.gov (United States)

2010-04-01

... (fermentation-derived). 184.1685 Section 184.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... (animal-derived) and chymosin preparation (fermentation-derived). (a)(1) Rennet and bovine rennet are... clear solution containing the active enzyme chymosin (E.C. 3.4.23.4). It is derived, via fermentation...

Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

Science.gov (United States)

van Beers, Eduard J.; Schaap, Marianne C.L.; Berckmans, René J.; Nieuwland, Rienk; Sturk, Augueste; van Doormaal, Frederiek F.; Meijers, Joost C.M.; Biemond, Bart J.

2009-01-01

Background Sickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease. Design and Methods In the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease. Results The majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=−0.58, pmicroparticles (r=0.63, p0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023). Conclusions We conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles. PMID:19815831

Structure-activity of valencenoid derivatives and their repellence to the Formosan subterranean termite.

Science.gov (United States)

Zhu, Betty C R; Henderson, Gregg; Sauer, Anne M; Yu, Ying; Crowe, William; Laine, Roger A

2003-12-01

Eight valencenoid derivatives were evaluated for their repelling activity against Formosan subterranean termites, Coptotermes formosanus Shiraki. Among them, 1,10-dihydronootkatone was the strongest repellent, and valencene was the weakest. Results of the structure-repellency relationships indicated (1) reduction of the ketone group to the alcohol on position 2 of nootkatone curtailed the activity; (2) because of the low activity of valencene relative to nootkatone that the ketone group was essential for repellent activity; (3) reduction of the 1,10 double bond (1,10-dihydronootkatone and tetrahydronootkatone) produced compounds more repellent than nootkatone; (4) the isopropenyl group probably does not participate in binding as evidenced by no significant difference in the repellent activity among nootkatone (double bond between position 11 and 12), isonootkatone (double bond between position 7 and 11), and 11,12-dihydronootkatone.

Synthesis of novel kavain-like derivatives and evaluation of their cytotoxic activity

Energy Technology Data Exchange (ETDEWEB)

Amaral, Patricia de A.; Agustini, Taciane; Eifler-Lima, Vera L. [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (Brazil). Faculdade de Farmacia. Lab. de Sintese Organica Medicinal; Petrignet, Julien; Cariou, Alexandre; Gree, Rene [Universite de Rennes 1, Rennes (France). Lab. de Chimie Therapeutique; Gouault, Nicolas; Lohezic-Ledevehat, Francoise; David, Michele [CNRS UMR, Universite de Rennes 1, Rennes (France). Lab. de Chimie et Photonique Moleculaires

2009-07-01

Palladium-catalyzed cross coupling reactions (Sonogashira-Hagihara, Suzuki-Miyaura, and Heck) coupling and nickel hydride-mediated tandem isomerization aldolisation have been used for the synthesis of three series of {delta}-valerolactones substituted in positions 3, 4, 5 and 6 of the lactone ring. The 26 kavaien-like derivatives were tested against three cell lines and five of them exhibited a weak cytotoxic activity. (author)

STRUCTURE – ANTIOXIDANT ACTIVITIES RELATIONSHIP ANALYSIS OF ISOEUGENOL, EUGENOL, VANILIN AND THEIR DERIVATIVES

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Nur Aini

2010-06-01

Full Text Available Structure Activity Relationship (SAR technique between the theoretical parameters and antioxidant activities of isoeugenol, eugenol, vanillin and their derivatives as Mannich reaction products, have been analyzed. Antioxidant activities were examined by oxidation reaction of oleic acid at 60 °C with b-carotene methods, whereas theoretical parameters of the activities were determined by calculating Bonding Dissociation Enthalpy (BDE and net charge of oxygen atom(-OH using AM1 semi empiric methods. The result from both test showed in the following orders: BHT > Mannich product of isoeugenol > isoeugenol > Mannich product of eugenol > eugenol > Mannich product of vanillin > vanillin. The antioxidant activities increase with small the BDE value and high the net charge. Electron donating groups will increase the antioxidants activity with lowering the BDE value and increasing the net charge, while electron-withdrawing groups will decrease antioxidants activity.   Keywords: SAR, antioxidants, Bonding Dissociation Entalphy, eugenol.

The antimicrobial efficacy and structure activity relationship of novel carbohydrate fatty acid derivatives against Listeria spp. and food spoilage microorganisms.

Science.gov (United States)

Nobmann, Patricia; Smith, Aoife; Dunne, Julie; Henehan, Gary; Bourke, Paula

2009-01-15

Novel mono-substituted carbohydrate fatty acid (CFA) esters and ethers were investigated for their antibacterial activity against a range of pathogenic and spoilage bacteria focussing on Listeria monocytogenes. Carbohydrate derivatives with structural differences enable comparative studies on the structure/activity relationship for antimicrobial efficacy and mechanism of action. The antimicrobial efficacy of the synthesized compounds was compared with commercially available compounds such as monolaurin and monocaprylin, as well as the pure free fatty acids, lauric acid and caprylic acid, which have proven antimicrobial activity. Compound efficacy was compared using an absorbance based broth microdilution assay to determine the minimum inhibitory concentration (MIC), increase in lag phase and decrease in maximum growth rate. Among the carbohydrate derivatives synthesized, lauric ether of methyl alpha-d-glucopyranoside and lauric ester of methyl alpha-d-mannopyranoside showed the highest growth-inhibitory effect with MIC values of 0.04 mM, comparable to monolaurin. CFA derivatives were generally more active against Gram positive bacteria than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy, which requires further investigation. This class of CFA derivatives has great potential for developing antibacterial agents relevant to the food industry, particularly for control of Listeria or other Gram-positive pathogens.

The Arbitrage Pricing Model: A Pedagogic Derivation and a Spreadsheet-Based Illustration

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Clarence C. Y. Kwan

2016-05-01

Full Text Available This paper derives, from a pedagogic perspective, the Arbitrage Pricing Model, which is an important asset pricing model in modern finance. The derivation is based on the idea that, if a self-financed investment has no risk exposures, the payoff from the investment can only be zero. Microsoft Excel plays an important pedagogic role in this paper. The Excel illustration not only helps students recognize more fully the various nuances in the model derivation, but also serves as a good starting point for students to explore on their own the relevance of the noise issue in the model derivation.

Fully Employing Software Inspections Data

Science.gov (United States)

Shull, Forrest; Feldmann, Raimund L.; Seaman, Carolyn; Regardie, Myrna; Godfrey, Sally

2009-01-01

Software inspections provide a proven approach to quality assurance for software products of all kinds, including requirements, design, code, test plans, among others. Common to all inspections is the aim of finding and fixing defects as early as possible, and thereby providing cost savings by minimizing the amount of rework necessary later in the lifecycle. Measurement data, such as the number and type of found defects and the effort spent by the inspection team, provide not only direct feedback about the software product to the project team but are also valuable for process improvement activities. In this paper, we discuss NASA's use of software inspections and the rich set of data that has resulted. In particular, we present results from analysis of inspection data that illustrate the benefits of fully utilizing that data for process improvement at several levels. Examining such data across multiple inspections or projects allows team members to monitor and trigger cross project improvements. Such improvements may focus on the software development processes of the whole organization as well as improvements to the applied inspection process itself.

Lactoferrin-derived Peptides Active towards Influenza: Identification of Three Potent Tetrapeptide Inhibitors.

Science.gov (United States)

Scala, Maria Carmina; Sala, Marina; Pietrantoni, Agostina; Spensiero, Antonia; Di Micco, Simone; Agamennone, Mariangela; Bertamino, Alessia; Novellino, Ettore; Bifulco, Giuseppe; Gomez-Monterrey, Isabel M; Superti, Fabiana; Campiglia, Pietro

2017-09-06

Bovine lactoferrin is a biglobular multifunctional iron binding glycoprotein that plays an important role in innate immunity against infections. We have previously demonstrated that selected peptides from bovine lactoferrin C-lobe are able to prevent both Influenza virus hemagglutination and cell infection. To deeper investigate the ability of lactoferrin derived peptides to inhibit Influenza virus infection, in this study we identified new bovine lactoferrin C-lobe derived sequences and corresponding synthetic peptides were synthesized and assayed to check their ability to prevent viral hemagglutination and infection. We identified three tetrapeptides endowed with broad anti-Influenza activity and able to inhibit viral infection in a concentration range femto- to picomolar. Our data indicate that these peptides may constitute a non-toxic tool for potential applications as anti-Influenza therapeutics.

Macroporous Activated Carbon Derived from Rapeseed Shell for Lithium–Sulfur Batteries

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Mingbo Zheng

2017-10-01

Full Text Available Lithium–sulfur batteries have drawn considerable attention because of their extremely high energy density. Activated carbon (AC is an ideal matrix for sulfur because of its high specific surface area, large pore volume, small-size nanopores, and simple preparation. In this work, through KOH activation, AC materials with different porous structure parameters were prepared using waste rapeseed shells as precursors. Effects of KOH amount, activated temperature, and activated time on pore structure parameters of ACs were studied. AC sample with optimal pore structure parameters was investigated as sulfur host materials. Applied in lithium–sulfur batteries, the AC/S composite (60 wt % sulfur exhibited a high specific capacity of 1065 mAh g−1 at 200 mA g−1 and a good capacity retention of 49% after 1000 cycles at 1600 mA g−1. The key factor for good cycling stability involves the restraining effect of small-sized nanopores of the AC framework on the diffusion of polysulfides to bulk electrolyte and the loss of the active material sulfur. Results demonstrated that AC materials derived from rapeseed shells are promising materials for sulfur loading.

Assimilation of SMOS-derived soil moisture in a fully integrated hydrological and soil-vegetation-atmosphere transfer model in Western Denmark

DEFF Research Database (Denmark)

Ridler, Marc-Etienne Francois; Madsen, Henrik; Stisen, Simon

2014-01-01

-derived soil moisture assimilation in a catchment scale model is typically restricted by two challenges: (1) passive microwave is too coarse for direct assimilation and (2) the data tend to be biased. The solution proposed in this study is to disaggregate the SMOS bias using a higher resolution land cover...... classification map that was derived from Landsat thermal images. Using known correlations between SMOS bias and vegetation type, the assimilation filter is adapted to calculate biases online, using an initial bias estimate. Real SMOS-derived soil moisture is assimilated in a precalibrated catchment model...

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

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Bernd Schmidt

2014-05-01

Full Text Available Cross metathesis of a lactate derived allylic alcohol and acrolein is the entry point to a de novo synthesis of 4-benzoate protected L-amicetose and a cinerulose derivative protected at C5 and C1.

Synthesis and structure activity relationships of carbamimidoylcarbamate derivatives as novel vascular adhesion protein-1 inhibitors.

Science.gov (United States)

Yamaki, Susumu; Yamada, Hiroyoshi; Nagashima, Akira; Kondo, Mitsuhiro; Shimada, Yoshiaki; Kadono, Keitaro; Yoshihara, Kosei

2017-11-01

Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted structural optimization of the glycine amide derivative 1, which we previously reported as a novel VAP-1 inhibitor, to improve stability in dog and monkey plasma, and aqueous solubility. By chemical modification of the right part in the glycine amide derivative, we identified the carbamimidoylcarbamate derivative 20c, which showed stability in dog and monkey plasma while maintaining VAP-1 inhibitory activity. We also found that conversion of the pyrimidine ring in 20c into saturated rings was effective for improving aqueous solubility. This led to the identification of 28a and 35 as moderate VAP-1 inhibitors with excellent aqueous solubility. Further optimization led to the identification of 2-fluoro-3-{3-[(6-methylpyridin-3-yl)oxy]azetidin-1-yl}benzyl carbamimidoylcarbamate (40b), which showed similar human VAP-1 inhibitory activity to 1 with improved aqueous solubility. 40b showed more potent ex vivo efficacy than 1, with rat plasma VAP-1 inhibitory activity of 92% at 1h after oral administration at 0.3mg/kg. In our pharmacokinetic study, 40b showed good oral bioavailability in rats, dogs, and monkeys, which may be due to its improved stability in dog and monkey plasma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

Science.gov (United States)

Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

2009-01-01

Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

7 CFR 718.304 - Failure to fully comply.

Science.gov (United States)

2010-01-01

... authorized in accordance with § 718.305 if the participant made a good faith effort to comply fully with the... FSA approval official to have made a good faith effort to comply fully with the terms and conditions...

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

Science.gov (United States)

Cortese-Krott, Miriam M.; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.; Suschek, Christoph V.

2014-01-01

Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. PMID:25180171

Comparative antimicrobial activity and mechanism of action of bovine lactoferricin-derived synthetic peptides.

Science.gov (United States)

Liu, Yifan; Han, Feifei; Xie, Yonggang; Wang, Yizhen

2011-12-01

Lactoferricin B (LfcinB), a 25 residue peptide derived from the N-terminal of bovine lactoferrin (bLF), causes depolarization of the cytoplasmic membrane in susceptible bacteria. Its mechanism of action, however, still needs to be elucidated. In the present study, synthetic LfcinB (without a disulfide bridge) and LfcinB (C-C; with a disulfide bridge) as well as three derivatives with 15-, 11- and 9-residue peptides were prepared to investigate their antimicrobial nature and mechanisms. The antimicrobial properties were measured via minimum inhibitory concentration (MIC) determinations, killing kinetics assays and synergy testing, and hemolytic activities were assessed by hemoglobin release. Finally, the morphology of peptide-treated bacteria was determined by atomic force microscopy (AFM). We found that there was no difference in MICs between LfcinB and LfcinB (C-C). Among the derivatives, only LfcinB15 maintained nearly the same level as LfcinB, in the MIC range of 16-128 μg/ml, and the MICs of LfcinB11 (64-256 μg/ml) were 4 times more than LfcinB, while LfcinB9 exhibited the lowest antimicrobial activity. When treated at MIC for 1 h, many blebs were formed and holes of various sizes appeared on the cell surface, but the cell still maintained its integrity. This suggested that LfcinB had a major permeability effect on the cytoplasmic membrane of both Gram-positive and Gram-negative bacteria, which also indicated it may be a possible intracellular target. Among the tested antibiotics, aureomycin increased the bactericidal activity of LfcinB against E. coli, S. aureus and P. aeruginosa, but neomycin did not have such an effect. We also found that the combination of cecropin A and LfcinB had synergistic effects against E. coli.

A Fully Automated Method to Detect and Segment a Manufactured Object in an Underwater Color Image

Science.gov (United States)

Barat, Christian; Phlypo, Ronald

2010-12-01

We propose a fully automated active contours-based method for the detection and the segmentation of a moored manufactured object in an underwater image. Detection of objects in underwater images is difficult due to the variable lighting conditions and shadows on the object. The proposed technique is based on the information contained in the color maps and uses the visual attention method, combined with a statistical approach for the detection and an active contour for the segmentation of the object to overcome the above problems. In the classical active contour method the region descriptor is fixed and the convergence of the method depends on the initialization. With our approach, this dependence is overcome with an initialization using the visual attention results and a criterion to select the best region descriptor. This approach improves the convergence and the processing time while providing the advantages of a fully automated method.

Xanthene derivatives increase glucose utilization through activation of LKB1-dependent AMP-activated protein kinase.

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Yonghoon Kwon

Full Text Available 5' AMP-activated protein kinase (AMPK is a highly conserved serine-threonine kinase that regulates energy expenditure by activating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. Therefore AMPK activators are considered to be drug targets for treatment of metabolic diseases such as diabetes mellitus. To identify novel AMPK activators, we screened xanthene derivatives. We determined that the AMPK activators 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-nitro-phenyl-thioureido]-ethyl}-amide (Xn and 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-cyano-phenyl-thioureido]-ethyl}-amide (Xc elevated glucose uptake in L6 myotubes by stimulating translocation of glucose transporter type 4 (GLUT4. Treatment with the chemical AMPK inhibitor compound C and infection with dominant-negative AMPKa2-virus inhibited AMPK phosphorylation and glucose uptake in myotubes induced by either Xn or Xc. Of the two major upstream kinases of AMPK, we found that Xn and Xc showed LKB1 dependency by knockdown of STK11, an ortholog of human LKB1. Single intravenous administration of Xn and Xc to high-fat diet-induced diabetic mice stimulated AMPK phosphorylation of skeletal muscle and improved glucose tolerance. Taken together, these results suggest that Xn and Xc regulate glucose homeostasis through LKB1-dependent AMPK activation and that the compounds are potential candidate drugs for the treatment of type 2 diabetes mellitus.

Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity.

Science.gov (United States)

Mbaba, Mziyanda; Mabhula, Amanda N; Boel, Natasha; Edkins, Adrienne L; Isaacs, Michelle; Hoppe, Heinrich C; Khanye, Setshaba D

2017-07-01

A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity compared to organic analogues 5a-b and 5e-f. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and antimicrobial activities of new 4-thiazolidones derived from formipyridine thiosemicarbazones

International Nuclear Information System (INIS)

Vercoza, George Leonardo; Feitoza, Danniel Delmondes; Alves, Antonio Jose; Aquino, Thiago Mendonca de; Lima, Jose Gildo de; Araujo, Janete Magali; Cunha, Ivana Glaucia B.; Goes, Alexandre Jose da Silva

2009-01-01

Twelve novel 4-thiazolidinone derivatives (2a-l) have been synthesized by reacting formylpyridine thiosemicarbazones (1a-l) and anhydride maleic in toluene. Their chemical structures were confirmed by IR, 1 H and 13 C NMR. The new compounds were submitted to in vitro evaluation against pathogenic Gram-positive, Gram-negative bacteria and yeasts. The findings obtained showed that the compounds 2a, 2d, 2e and 2g were effective against some of the bacterial strains used, whereas the compounds 2d, 2e and 2i exhibited a moderate antifungal activity against the yeast strains evaluated. An initial structure activity relationship (SAR) was established. (author)

Fully Integrated Biochip Platforms for Advanced Healthcare

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Giovanni De Micheli

2012-08-01

Full Text Available Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.

Synthesis and trypanocidal activity of 7, 2'-dioxygenated isoflavones and oxypropanolamine derivatives

Energy Technology Data Exchange (ETDEWEB)

Faria, Terezinha de J. [Universidade Estadual de Londrina, PR (Brazil). Dept. de Quimica]. E-mail: tjfaria@uel.br; Silva, Luiz G. Fonseca e; Souza Filho, Jose D. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Quimica; Chiari, Egler [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Parasitologia; Oliveira, Alaide B. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Dept. de Produtos Farmaceuticos

2005-11-15

'-Dihydroxyisoflavone was shown to be active against the bloodstream trypomastigote form of Trypanosoma cruzi, the etiologic agent of Chagas' disease. Amphiphilic derivatives of this isoflavone were synthesized aiming to obtain hydrosoluble compounds of potential use as prophylactic agents to be added to blood for transfusion. This isoflavone was obtained by demethylation of 7-hydroxy-2'-methoxyisoflavone that was synthesized via the intermediate deoxybenzoin. Its reaction with epichlorohydrin, followed by aminolysis with diethylamine, afforded the 7-oxypropanolamine which on treatment with methyl iodide gave the corresponding ammonium salt. The 7-hydroxy-2'-methoxyisoflavone was inactive in the in vitro assays, the 7-oxypropanolamine was more active than 7, 2'-dihydroxyisoflavone while the ammonium salt has not eliminated the parasite from the blood besides causing total lysis of the erythrocytes. The simple synthetic procedures described in the present paper can be used to provide gram quantities of 7, 2'-dihydroxyisoflavone and its 7-oxypropanolamine derivative that should be further investigated in in vivo murine models as potential chemotherapeutic agents for treatment of Chagas' disease. (author)

Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives.

Science.gov (United States)

Bassyouni, Fatma A; Saleh, Tamer S; ElHefnawi, Mahmoud M; Abd El-Moez, Sherein I; El-Senousy, Waled M; Abdel-Rehim, Mohamed E

2012-12-01

Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1H-benzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4",5"-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophore-based correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking

Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

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Carolina de la Guardia

2018-03-01

Full Text Available Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.

Antioxidant and DPPH (1,1-diphenyl-2-picrylhydrazyl Free Radical Scavenging Activities of Boniger Acid and Calix[4]arene Derivative

Directory of Open Access Journals (Sweden)

E. ERDEM

2014-07-01

Full Text Available Diazonium derivative of calix[4]arene has been synthesized using three different synthetic steps. Initially p-tert-butylcalix[4]arene was synthesized with the condensation reaction of p-tert-butylphenol and formaldehyde in basic conditions. Calix[4]arene was obtained after the debutylation reaction of p-tert-butylcalix[4]arene with AlCl3. Calix[4]arene reacted with diazonium salt of Böniger acid to yield the 5,17-[(Bis(azo-bis(5-hydroxy-2,7-naphthalenedisulfonicacid]-25,26,27,28-tetrahydroxy calix[4]arene which has eight free phenolic hydroxyl group. Reaction steps were shown in Fig.1.2,7-naphthalenedisulfonicacid]-25,26,27,28-tetrahydroxy calix[4]arene The antioxidant activity of the Böniger acid and calix[4]aren derivative were determined using β-karotene-linoleic acid system. Moreover, the free radical scavenging activity values were tested with DPPH free radical. The two compounds showed strong antioxidant activity. Total antioxidant activity of Böniger acid and calix[4]aren derivative was determined using β–carotenelinoleic acid model system and was found the antioxidant activity of 84.00% and 85.60 % respectively. The free radical scavenging activities were determined as 83.05% and 84.69 %. Results show that, two compounds has the antioxidant activity. The calix[4]aren derivaties has more higher activity then Boniger acid because of calix[4]aren derivative has much hydroxl groups.

Transmembrane Tumor Necrosis Factor Controls Myeloid-Derived Suppressor Cell Activity via TNF Receptor 2 and Protects from Excessive Inflammation during BCG-Induced Pleurisy

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Leslie Chavez-Galan

2017-08-01

Full Text Available Pleural tuberculosis (TB is a form of extra-pulmonary TB observed in patients infected with Mycobacterium tuberculosis. Accumulation of myeloid-derived suppressor cells (MDSC has been observed in animal models of TB and in human patients but their role remains to be fully elucidated. In this study, we analyzed the role of transmembrane TNF (tmTNF in the accumulation and function of MDSC in the pleural cavity during an acute mycobacterial infection. Mycobacterium bovis BCG-induced pleurisy was resolved in mice expressing tmTNF, but lethal in the absence of tumor necrosis factor. Pleural infection induced MDSC accumulation in the pleural cavity and functional MDSC required tmTNF to suppress T cells as did pleural wild-type MDSC. Interaction of MDSC expressing tmTNF with CD4 T cells bearing TNF receptor 2 (TNFR2, but not TNFR1, was required for MDSC suppressive activity on CD4 T cells. Expression of tmTNF attenuated Th1 cell-mediated inflammatory responses generated by the acute pleural mycobacterial infection in association with effective MDSC expressing tmTNF and interacting with CD4 T cells expressing TNFR2. In conclusion, this study provides new insights into the crucial role played by the tmTNF/TNFR2 pathway in MDSC suppressive activity required during acute pleural infection to attenuate excessive inflammation generated by the infection.

An evaluation of the physiological activity of 9-amine-9-fluorenephosphonic acid derivatives

Directory of Open Access Journals (Sweden)

Henryk Skrabka

2013-12-01

Full Text Available The physiological activity of eleven 9-amine-9-fluorenephosphonic acid derivatives, synthesized at the Wrocław Polytechnic, was examined. The test plant was Spirodela oligorrhiza. The effect of these compounds on the increase of the dry matter of this plant was tested in eight-day experiments. The activity of the compounds was varied. The most toxic were nos. 2, 4, 9, 8, 5 and 6 which were lethal in low concentrations. Somewhat less toxic were nos. 7, 10 and 11; nos. 1 and 3 were the least toxic.

Highly Accurate Derivatives for LCL-Filtered Grid Converter with Capacitor Voltage Active Damping

DEFF Research Database (Denmark)

Xin, Zhen; Loh, Poh Chiang; Wang, Xiongfei

2016-01-01

The middle capacitor voltage of an LCL-filter, if fed back for synchronization, can be used for active damping. An extra sensor for measuring the capacitor current is then avoided. Relating the capacitor voltage to existing popular damping techniques designed with capacitor current feedback would...... are then proposed, based on either second-order or non-ideal generalized integrator. Performances of these derivatives have been found to match the ideal “s” function closely. Active damping based on capacitor voltage feedback can therefore be realized accurately. Experimental results presented have verified...

Theoretical effects of fully ductile versus fully brittle behaviors of bone tissue on the strength of the human proximal femur and vertebral body.

Science.gov (United States)

Nawathe, Shashank; Yang, Haisheng; Fields, Aaron J; Bouxsein, Mary L; Keaveny, Tony M

2015-05-01

The influence of the ductility of bone tissue on whole-bone strength represents a fundamental issue of multi-scale biomechanics. To gain insight, we performed a computational study of 16 human proximal femurs and 12 T9 vertebral bodies, comparing the whole-bone strength for the two hypothetical bounding cases of fully brittle versus fully ductile tissue-level failure behaviors, all other factors, including tissue-level elastic modulus and yield stress, held fixed. For each bone, a finite element model was generated (60-82 μm element size; up to 120 million elements) and was virtually loaded in habitual (stance for femur, compression for vertebra) and non-habitual (sideways fall, only for femur) loading modes. Using a geometrically and materially non-linear model, the tissue was assumed to be either fully brittle or fully ductile. We found that, under habitual loading, changing the tissue behavior from fully ductile to fully brittle reduced whole-bone strength by 38.3±2.4% (mean±SD) and 39.4±1.9% for the femur and vertebra, respectively (p=0.39 for site difference). These reductions were remarkably uniform across bones, but (for the femur) were greater for non-habitual (57.1±4.7%) than habitual loading (pductile cases. These theoretical results suggest that the whole-bone strength of the proximal femur and vertebra can vary substantially between fully brittle and fully ductile tissue-level behaviors, an effect that is relatively insensitive to bone morphology but greater for non-habitual loading. Copyright © 2015 Elsevier Ltd. All rights reserved.

Combinatorial Drug Testing in 3D Microtumors Derived from GBM Patient-Derived Xenografts Reveals Cytotoxic Synergy in Pharmacokinomics-informed Pathway Interactions.

Science.gov (United States)

Gilbert, Ashley N; Anderson, Joshua C; Duarte, Christine W; Shevin, Rachael S; Langford, Catherine P; Singh, Raj; Gillespie, G Yancey; Willey, Christopher D

2018-05-30

Glioblastoma multiforme (GBM), the most common form of primary malignant brain cancer in adults, is a devastating disease for which effective treatment has remained elusive for over 75 years. One reason for the minimal progress during this time is the lack of accurate preclinical models to represent the patient's tumor's in vivo environment, causing a disconnect in drug therapy effectiveness between the laboratory and clinic. While patient-derived xenografts (PDX's or xenolines) are excellent human tumor representations, they are not amenable to high throughput testing. Therefore, we developed a miniaturized xenoline system (microtumors) for drug testing. Nineteen GBM xenolines were profiled for global kinase (kinomic) activity revealing actionable kinase targets associated with intracranial tumor growth rate. Kinase inhibitors for these targets (WP1066, selumetinib, crizotinib, and cediranib) were selected for single and combination therapy using a fully human-derived three-dimensional (3D) microtumor model of GBM xenoline cells embedded in HuBiogel for subsequent molecular and phenotype assays. GBM microtumors closely resembled orthotopically-implanted tumors based on immunohistochemical analysis and displayed kinomic and morphological diversity. Drug response testing could be reproducibly performed in a 96-well format identifying several synergistic combinations. Our findings indicate that 3D microtumors can provide a suitable high-throughput model for combination drug testing.

Biology-Oriented Syntheses (BIOS) of Novel Santonic-1,3,4-oxadiazole Derivatives under Microwave-Irradiation and their Antimicrobial Activity

International Nuclear Information System (INIS)

Salar, U.; Khan, K. M.; Naz, F.; Siddiqui, N. I.

2015-01-01

Novel 2-thio substituted 1,3,4-oxadiazole derivatives of santonic acid (13-18) were synthesized. The synthesis of these derivatives was comprised of six steps which start from the basic hydrolysis of santonin 1 to the santoninic acid 2 followed by in situ rearrangement of 2 into santonic acid 3. Santonic acid 3 was then converted into its acyl imidazole derivative 4 followed by hydrazinolysis to give santonic carbohydrazide 5 which was further converted into santonic-1,3,4-oxadiazole-2-thiol 6. Santonic-1,3,4-oxadiazole-2-thiol 6 was alkylated to afford 2-thio substituted 1,3,4-oxadiazole derivatives of santonic acid (13-18). All the synthetic steps were carried out under microwave irradiation in controlled parameters. Compounds 13-18 along with intervening intermediates 5 and 6 were evaluated for their antimicrobial potential. Compound 14 showed appreciably good activity against Staphylococcus epidermidis. On the other hand compounds 6 and 17 demonstrated good activity against Escherichia coli and Shigella flexeneri, respectively. Compound 6 showed good antifungal activity. The synthesized compounds were characterized by different spectroscopy techniques. (author)

Complete assignments of NMR data and assessment of trypanocidal activity of new eremantholide C derivatives

Energy Technology Data Exchange (ETDEWEB)

Saude-Guimaraes, Denia Antunes, E-mail: saude@ef.ufop.br, E-mail: saudeguima@gmail.com [Universidade Federal de Ouro Preto (UFOP), MG (Brazil); Raslan, Delio S.; Chiari, Egler; Oliveira, Alaide B. de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2014-12-15

Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1’,2’- epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1’,2’-epoxyeremantholide C (3), 5-n-propylammonium-4,5-dihydro-1’,2’-epoxyeremantholide C chloride (4), 5-n-propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide C (6). The structures of all these derivatives were assigned on the basis of IR, MS, {sup 1}H and {sup 13}C NMR data by 1D and 2D techniques. Eremantholide C and the derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the parasites strains while all derivatives were partially active against the CL strain and inactive against the Y strain. (author)

Activated platelet-derived growth factor β receptor and Ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.