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Sample records for structure-activity relationship investigation

  1. Synthesis and anticancer structure activity relationship investigation of cationic anthraquinone analogs.

    Science.gov (United States)

    Shrestha, Jaya P; Fosso, Marina Y; Bearss, Jeremiah; Chang, Cheng-Wei Tom

    2014-04-22

    We have synthesized a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which can be viewed as analogs of cationic anthraquinones. Unlike the similar analogs that we have reported previously, these compounds show relatively weak antibacterial activities but exert strong anticancer activities (low μM to nM GI50), in particular, against melanoma, colon cancer, non-small cell lung cancer and central nervous system (CNS) cancer. These compounds are structurally different from their predecessors by having the aromatic group, instead of alkyl chains, directly attached to the cationic anthraquinone scaffold. Further investigation in the structure-activity relationship (SAR) reveals the significant role of electron donating substituents on the aromatic ring in enhancing the anticancer activities via resonance effect. Steric hindrance of these groups is disadvantageous but is less influential than the resonance effect. The difference in the attached groups at N-1 position of the cationic anthraquinone analog is the main structural factor for the switching of biological activity from antibacterial to anticancer. The discovery of these compounds may lead to the development of novel cancer chemotherapeutics. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Investigating the Structure-Activity Relationship of the Insecticidal Natural Product Rocaglamide.

    Science.gov (United States)

    Hall, Roger G; Bruce, Ian; Cooke, Nigel G; Diorazio, Louis J; Cederbaum, Fredrik; Dobler, Markus R; Irving, Ed

    2017-12-01

    The natural product Rocaglamide (1), isolated from the tree Aglaia elliptifolia, is a compelling but also challenging lead structure for crop protection. In laboratory assays, the natural product shows highly interesting insecticidal activity against chewing pests and beetles, but also phytotoxicity on some crop plants. Multi-step syntheses with control of stereochemistry were required to probe the structure-activity relationship (SAR), and seek simplified analogues. After a significant research effort, just two areas of the molecule were identified which allow modification whilst maintaining activity, as will be highlighted in this paper.

  3. Investigation of Antileishmanial Activities of Acridines Derivatives against Promastigotes and Amastigotes Form of Parasites Using Quantitative Structure Activity Relationship Analysis

    Directory of Open Access Journals (Sweden)

    Samir Chtita

    2016-01-01

    Full Text Available In a search of newer and potent antileishmanial (against promastigotes and amastigotes form of parasites drug, a series of 60 variously substituted acridines derivatives were subjected to a quantitative structure activity relationship (QSAR analysis for studying, interpreting, and predicting activities and designing new compounds by using multiple linear regression and artificial neural network (ANN methods. The used descriptors were computed with Gaussian 03, ACD/ChemSketch, Marvin Sketch, and ChemOffice programs. The QSAR models developed were validated according to the principles set up by the Organisation for Economic Co-operation and Development (OECD. The principal component analysis (PCA has been used to select descriptors that show a high correlation with activities. The univariate partitioning (UP method was used to divide the dataset into training and test sets. The multiple linear regression (MLR method showed a correlation coefficient of 0.850 and 0.814 for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. Internal and external validations were used to determine the statistical quality of QSAR of the two MLR models. The artificial neural network (ANN method, considering the relevant descriptors obtained from the MLR, showed a correlation coefficient of 0.933 and 0.918 with 7-3-1 and 6-3-1 ANN models architecture for antileishmanial activities against promastigotes and amastigotes forms of parasites, respectively. The applicability domain of MLR models was investigated using simple and leverage approaches to detect outliers and outsides compounds. The effects of different descriptors in the activities were described and used to study and design new compounds with higher activities compared to the existing ones.

  4. Identification of residues important for the activity of aldehyde-deformylating oxygenase through investigation into the structure-activity relationship.

    Science.gov (United States)

    Wang, Qing; Bao, Luyao; Jia, Chenjun; Li, Mei; Li, Jian-Jun; Lu, Xuefeng

    2017-03-16

    Aldehyde-deformylating oxygenase (ADO) is a key enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, cADO (cyanobacterial ADO) showed extreme low activity with the k cat value below 1 min -1 , which would limit its application in biofuel production. To identify the activity related key residues of cADO is urgently required. The amino acid residues which might affect cADO activity were identified based on the crystal structures and sequence alignment of cADOs, including the residues close to the di-iron center (Tyr39, Arg62, Gln110, Tyr122, Asp143 of cADO-1593), the protein surface (Trp 178 of cADO-1593), and those involved in two important hydrogen bonds (Gln49, Asn123 of cADO-1593, and Asp49, Asn123 of cADO-sll0208) and in the oligopeptide whose conformation changed in the absence of the di-iron center (Leu146, Asn149, Phe150 of cADO-1593, and Thr146, Leu148, Tyr150 of cADO-sll0208). The variants of cADO-1593 from Synechococcus elongatus PCC7942 and cADO-sll0208 from Synechocystis sp. PCC6803 were constructed, overexpressed, purified and kinetically characterized. The k cat values of L146T, Q49H/N123H/F150Y and W178R of cADO-1593 and L148R of cADO-sll0208 were increased by more than two-fold, whereas that of R62A dropped by 91.1%. N123H, Y39F and D143A of cADO-1593, and Y150F of cADO-sll0208 reduced activities by ≤ 20%. Some important amino acids, which exerted some effects on cADO activity, were identified. Several enzyme variants exhibited greatly reduced activity, while the k cat values of several mutants are more than two-fold higher than the wild type. This study presents the report on the relationship between amino acid residues and enzyme activity of cADOs, and the information will provide a guide for enhancement of cADO activity through protein engineering.

  5. 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....

  6. Quantitative Structure-Activity Relationship Analysis of the ...

    African Journals Online (AJOL)

    Erah

    Quantitative Structure-Activity Relationship Analysis of the Anticonvulsant ... Two types of molecular descriptors, including the 2D autocorrelation ..... It is based on the simulation of natural .... clustering anticonvulsant, antidepressant, and.

  7. The Ghosts of Acetylcholine : structure-activity relationships of ...

    African Journals Online (AJOL)

    The Ghosts of Acetylcholine : structure-activity relationships of muscle relaxants : registrar communication. ... AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...

  8. Structure-activity relationship studies of citalopram derivatives

    DEFF Research Database (Denmark)

    Larsen, M Andreas B; Plenge, Per; Andersen, Jacob

    2016-01-01

    towards the S2 site. EXPERIMENTAL APPROACH: We performed a systematic structure-activity relationship study based on the scaffold of citalopram and the structurally closely related congener, talopram, that shows low-affinity S1 binding in SERT. The role of the four chemical substituents, which distinguish...... citalopram from talopram in conferring selectivity towards the S1 and S2 site, respectively, was assessed by determining the binding of 14 citalopram/talopram analogous to the S1 and S2 binding sites in SERT using membranes of COS7 cells transiently expressing SERT. KEY RESULTS: The structure-activity...

  9. 3-alkyl fentanyl analogues: Structure-activity-relationship study

    OpenAIRE

    Vučković, Sonja; Savić-Vujović, Katarina; Srebro, Dragana; Ivanović, Milovan; Došen-Mićović, Ljiljana; Stojanović, Radan; Prostran, Milica

    2012-01-01

    Introduction. Fentanyl belongs to 4-anilidopiperidine class of synthetic opioid analgesics. It is characterized by high potency, rapid onset and short duration of action. A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful analgesic drugs. Objective. In this study, newly synthesized 3-alkyl fentanyl analogues were examined for analgesic activity and compared with fentanyl. Methods. ...

  10. Structure-activity relationship of crustacean peptide hormones.

    Science.gov (United States)

    Katayama, Hidekazu

    2016-01-01

    In crustaceans, various physiological events, such as molting, vitellogenesis, and sex differentiation, are regulated by peptide hormones. To understanding the functional sites of these hormones, many structure-activity relationship (SAR) studies have been published. In this review, the author focuses the SAR of crustacean hyperglycemic hormone-family peptides and androgenic gland hormone and describes the detailed results of our and other research groups. The future perspectives will be also discussed.

  11. Structure and Structure-activity Relationship of Functional Organic Molecules

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Research theme The group is made up of junior scientists from the State Key Laboratory of Elemento-organic Chemistry, Nankai University.The scientists focus their studis on the structure and structure-activity relationship of functional organic molecules not only because it has been the basis of their research, but also because the functional study of organic compounds is now a major scientific issue for organic chemists around the world.

  12. Investigation of cytochrome P450 inhibitory properties of maslinic acid, a bioactive compound from Olea europaea L., and its structure-activity relationship.

    Science.gov (United States)

    Sun, Min; Tang, Yu; Ding, Tonggui; Liu, Mingyao; Wang, Xin

    2015-01-15

    Maslinic acid (MA), the main pentacyclic triterpene of Olea europaea L. fruit, possesses a variety of pharmacological actions, including hypoglycemic, antioxidant, cardioprotective and antitumoral activities. Despite its importance, little is known about its effects on the cytochrome P450 (CYP) activity in both humans and animals. Therefore, the aim of this study was to investigate the effects of MA on the CYP 1A2, 2C9/11, 2D1/6, 2E1 and 3A2/4 activities by human and rat liver microsomes and specific CYP isoforms. In humans, MA only weakly inhibited CYP3A4 activity in human liver microsomes and specific CYP3A4 isoform with IC50 value at 46.1 and 62.3µM, respectively. In rats, MA also exhibited weak inhibition on CYP2C11, CYP2E1 and CYP3A2 activities with IC50 values more than 100µM. Enzyme kinetic studies showed that the MA was not only a competitive inhibitor of CYP3A4 in humans, but also a competitive inhibitor of CYP2C11 and 3A2 in rats, with Ki of 18.4, 98.7 and 66.3µM, respectively. Moreover, the presence of hydroxyl group at C-2 position of triterpenic acid in MA compared with oleanolic acid could magnify its competitive inhibition on human CYP3A4 activity. The relatively high Ki values of MA would have a low potential to cause the possible toxicity and drug interactions involving CYP enzymes, thus suggesting a sufficient safety for its putative use as a nutraceutical taken together with drugs. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Chemistry and Structure-Activity Relationships of Psychedelics.

    Science.gov (United States)

    Nichols, David E

    2018-01-01

    This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT 2A receptor plays a key role in regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT 2A receptor is the principal mechanism of action for psychedelics, compounds with 5-HT 2A agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to activation of 5-HT 2A receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known.

  14. Designing a Quantitative Structure-Activity Relationship for the ...

    Science.gov (United States)

    Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemicals including nearly 8000 chemicals tested for in vitro bioactivity in the Tox21 program. To address this gap, a quantitative structure-activity relationship (QSAR) for intrinsic metabolic clearance rate was developed to offer reliable in silico predictions for a diverse array of chemicals. Models were constructed with curated in vitro assay data for both pharmaceutical-like chemicals (ChEMBL database) and environmentally relevant chemicals (ToxCast screening) from human liver microsomes (2176 from ChEMBL) and human hepatocytes (757 from ChEMBL and 332 from ToxCast). Due to variability in the experimental data, a binned approach was utilized to classify metabolic rates. Machine learning algorithms, such as random forest and k-nearest neighbor, were coupled with open source molecular descriptors and fingerprints to provide reasonable estimates of intrinsic metabolic clearance rates. Applicability domains defined the optimal chemical space for predictions, which covered environmental chemicals well. A reduced set of informative descriptors (including relative charge and lipophilicity) and a mixed training set of pharmaceuticals and environmentally relevant chemicals provided the best intr

  15. Structure activity relationships to assess new chemicals under TSCA

    Energy Technology Data Exchange (ETDEWEB)

    Auletta, A.E. [Environmental Protection Agency, Washington, DC (United States)

    1990-12-31

    Under Section 5 of the Toxic Substances Control Act (TSCA), manufacturers must notify the US Environmental Protection Agency (EPA) 90 days before manufacturing, processing, or importing a new chemical substance. This is referred to as a premanufacture notice (PMN). The PMN must contain certain information including chemical identity, production volume, proposed uses, estimates of exposure and release, and any health or environmental test data that are available to the submitter. Because there is no explicit statutory authority that requires testing of new chemicals prior to their entry into the market, most PMNs are submitted with little or no data. As a result, EPA has developed special techniques for hazard assessment of PMN chemicals. These include (1) evaluation of available data on the chemical itself, (2) evaluation of data on analogues of the PMN, or evaluation of data on metabolites or analogues of metabolites of the PMN, (3) use of quantitative structure activity relationships (QSARs), and (4) knowledge and judgement of scientific assessors in the interpretation and integration of the information developed in the course of the assessment. This approach to evaluating potential hazards of new chemicals is used to identify those that are most in need of addition review of further testing. It should not be viewed as a replacement for testing. 4 tabs.

  16. Modifiers in rhodium catalysts for carbon monoxide hydrogenation: Structure-activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Bhore, N. A.

    1989-05-01

    This report is aimed at identifying interesting modified rhodium systems and elucidating structure-activity relationships in these systems with the overall goal of understanding the scientific issues in the catalytic conversion of syngas to oxygenates. Specific additives (sodium and molybdenum) are selected based on the scoping experiments. The effect of the additives on supported rhodium catalysts is then investigated. Throughout the investigation, experiments and analysis were performed on real systems instead of ideal systems. 374 refs., 82 figs., 57 tabs.

  17. Structure-activity relationship of CART peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Elbert, Tomáš; Šanda, Miloslav; Slaninová, Jiřina; Železná, Blanka

    2007-01-01

    Roč. 88, č. 4 (2007), s. 565 ISSN 0006-3525. [American Peptide Society Symposium /20./. 26.06.2007-30.06.2007, Montreal] Institutional research plan: CEZ:AV0Z40550506 Keywords : cocaine and amphetamine regulated transcript peptide * structure * activity Subject RIV: CE - Biochemistry

  18. Accepting the Invitation to Open Innovation in Malaria Drug Discovery: Synthesis, Biological Evaluation, and Investigation on the Structure-Activity Relationships of Benzo[b]thiophene-2-carboxamides as Antimalarial Agents.

    Science.gov (United States)

    Pieroni, Marco; Azzali, Elisa; Basilico, Nicoletta; Parapini, Silvia; Zolkiewski, Michal; Beato, Claudia; Annunziato, Giannamaria; Bruno, Agostino; Vacondio, Federica; Costantino, Gabriele

    2017-03-09

    Malaria eradication is a global health priority, but current therapies are not always suitable for providing a radical cure. Artemisinin has paved the way for the current malaria treatment, the so-called Artemisinin-based Combination Therapy (ACT). However, with the detection of resistance to ACT, innovative compounds active against multiple parasite species and at multiple life stages are needed. GlaxoSmithKline has recently disclosed the results of a phenotypic screening of an internal library, publishing a collection of 400 antimalarial chemotypes, termed the "Malaria Box". After analysis of the data set, we have carried out a medicinal chemistry campaign in order to define the structure-activity relationships for one of the released compounds, which embodies a benzothiophene-2-carboxamide core. Thirty-five compounds were prepared, and a description of the structural features responsible for the in vitro activity against different strains of P. falciparum, the toxicity, and the metabolic stability is herein reported.

  19. Structure-Activity Relationships on the Molecular Descriptors Family Project at the End

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2007-12-01

    Full Text Available Molecular Descriptors Family (MDF on the Structure-Activity Relationships (SAR, a promising approach in investigation and quantification of the link between 2D and 3D structural information and the activity, and its potential in the analysis of the biological active compounds is summarized. The approach, attempts to correlate molecular descriptors family generated and calculated on a set of biological active compounds with their observed activity. The estimation as well as prediction abilities of the approach are presented. The obtained MDF SAR models can be used to predict the biological activity of unknown substrates in a series of compounds.

  20. Molecular Descriptors Family on Structure Activity Relationships 1. Review of the Methodology

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2005-01-01

    Full Text Available This review cumulates the knowledge about the use of Molecular Descriptors Family usage on Structure Activity Relationships. The methodology is augmented through the general Structure Activity Relationships methodology. The obtained models in a series of five papers are quantitatively analyzed by comparing with previous reported results by using of the correlated correlations tests. The scores for a series of 13 data sets unpublished yet results are presented. Two unrestricted online access portals to the Molecular Descriptors Family Structure Activity Relationship models results are given.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Structure-activity relationship of immunostimulatory effects of phthalates

    Directory of Open Access Journals (Sweden)

    Nielsen Gunnar D

    2008-10-01

    Full Text Available Abstract Background Some chemicals, including some phthalate plasticizers, have been shown to have an adjuvant effect in mice. However, an adjuvant effect, defined as an inherent ability to stimulate the humoral immune response, was only observed after exposure to a limited number of the phthalates. An adjuvant effect may be due to the structure or physicochemical characteristics of the molecule. The scope of this study was to investigate which molecular characteristics that determine the observed adjuvant effect of the most widely used phthalate plasticizer, the di-(2-ethylhexyl phthalate (DEHP, which is documented as having a strong adjuvant effect. To do so, a series of nine lipophilic compounds with structural and physicochemical relations to DEHP were investigated. Results Adjuvant effect of phthalates and related compounds were restricted to the IgG1 antibody formation. No effect was seen on IgE. It appears that lipophilicity plays a crucial role, but lipophilicity does not per se cause an adjuvant effect. In addition to lipophilicity, a phthalate must also possess specific stereochemical characteristics in order for it to have adjuvant effect. Conclusion The adjuvant effect of phthalates are highly influenced by both stereochemical and physico-chemical properties. This knowledge may be used in the rational development of plasticizers without adjuvant effect as well as in the design of new immunological adjuvants.

  3. Structure-activity relationships of heterogeneous catalysts from time-resolved X-ray absorption spectroscopy

    International Nuclear Information System (INIS)

    Ressler, T.; Jentoft, R.E.; Wienold, J.; Girgsdies, F.; Neisius, T.; Timpe, O.

    2003-01-01

    Knowing the composition and the evolution of the bulk structure of a heterogeneous catalyst under working conditions (in situ) is a pre-requisite for understanding structure-activity relationships. X-ray absorption spectroscopy can be employed to study a catalytically active material in situ. In addition to steady-state investigations, the technique permits experiments with a time-resolution in the sub-second range to elucidate the solid-state kinetics of the reactions involved. Combined with mass spectrometry, the evolution of the short-range order structure of a heterogeneous catalyst, the average valence of the constituent metals, and the phase composition can be obtained. Here we present results obtained from time-resolved studies on the reduction of MoO 3 in propene and in propene and oxygen

  4. Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression.

    Science.gov (United States)

    Toyota, Yosuke; Nomura, Sayaka; Makishima, Makoto; Hashimoto, Yuichi; Ishikawa, Minoru

    2017-06-15

    Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC 50 : 14μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Quantitative Structure-Activity Relationships and Docking Studies of Calcitonin Gene-Related Peptide Antagonists

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range...... of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression....... The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model...

  6. Structure-activity relationship studies of the aromatic positions in cyclopentapeptide CXCR4 antagonists

    DEFF Research Database (Denmark)

    Mungalpara, Jignesh; Zachariassen, Zack G; Thiele, Stefanie

    2013-01-01

    , and autoimmune diseases. While the structure-activity relationships for Arg(1), Arg(2), and Gly(4) are well established, less is understood about the roles of the aromatic residues 2-Nal(3) and D-Tyr(5). Here we report further structure-activity relationship studies of these two positions, which showed that (i......) the distal aromatic ring of the 2-Nal(3) side chain is required in order to maintain high potency and (ii) replacement of D-Tyr(5) with conformationally constrained analogues results in significantly reduced activity. However, a simplified analogue that contained Gly instead of D-Tyr(5) was only 13-fold less...

  7. A biology-based approach for quantitative structure-activity relationships (QSARs) in ecotoxicity.

    NARCIS (Netherlands)

    Jager, T.; Kooijman, S.A.L.M.

    2009-01-01

    Quantitative structure-activity relationships (QSARs) for ecotoxicity can be used to fill data gaps and limit toxicity testing on animals. QSAR development may additionally reveal mechanistic information based on observed patterns in the data. However, the use of descriptive summary statistics for

  8. Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

    NARCIS (Netherlands)

    Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik

    After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural

  9. Environmental properties of long-chain alcohols. Structure-activity Relationship for Chronic Aquatic Toxicity

    DEFF Research Database (Denmark)

    Schaefers, Christoph; Sanderson, Hans; Boshof, Udo

    2009-01-01

    Daphnia magna reproduction tests were performed with C10, C12, C14 and C15 alcohols to establish a structure-activity relationship of chronic effects of long-chain alcohols. The data generation involved substantial methodological efforts due to the exceptionally rapid biodegradability of the test...

  10. 3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships.

    Science.gov (United States)

    Dhar, T G Murali; Shen, Zhongqi; Gu, Henry H; Chen, Ping; Norris, Derek; Watterson, Scott H; Ballentine, Shelley K; Fleener, Catherine A; Rouleau, Katherine A; Barrish, Joel C; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

    2003-10-20

    A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.

  11. Structure-activity relationships of nucleoside analogues for inhibition of tick-borne encephalitis virus

    Czech Academy of Sciences Publication Activity Database

    Eyer, L.; Šmídková, Markéta; Nencka, Radim; Neča, J.; Kastl, T.; Palus, Martin; De Clercq, E.; Růžek, Daniel

    2016-01-01

    Roč. 133, Sep (2016), s. 119-129 ISSN 0166-3542 R&D Projects: GA MZd(CZ) NV16-34238A; GA ČR(CZ) GA16-20054S Institutional support: RVO:61388963 ; RVO:60077344 Keywords : structure-activity relationship * tick-borne encephalitis * nucleoside inhibitor * antiviral activity * cytotoxicity Subject RIV: CC - Organic Chemistry; EE - Microbiology, Virology (BC-A) Impact factor: 4.271, year: 2016

  12. Structure-activity relationship of a u-type antimicrobial microemulsion system.

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    Full Text Available The structure-activity relationship of a U-type antimicrobial microemulsion system containing glycerol monolaurate and ethanol at a 1∶1 mass ratio as oil phase and Tween 20 as surfactant were investigated along a water dilution line at a ratio of 80∶20 mass% surfactant/oil phase, based on a pseudo-ternary phase diagram. The differential scanning calorimetry results showed that in the region of up to 33% water, all water molecules are confined to the hydrophilic core of the reverse micelles, leading to the formation of w/o microemulsion. As the water content increases, the water gains mobility, and transforms into bicontinuous in the region of 33-39% water, and finally the microemulsion become o/w in the region of above 39% water. The microstructure characterization was confirmed by the dynamic light scattering measurements and freeze-fracture transmission electron microscope observation. The antimicrobial activity assay using kinetics of killing analysis demonstrated that the microemulsions in w/o regions exhibited relatively high antimicrobial activity against Escherichia coli and Staphylococcus aureus due to the antimicrobial oil phase as the continuous phase, while the antimicrobial activity started to decrease when the microemulsions entered the bicontinuous region, and decreased rapidly as the water content increased in the o/w region, as a result of the dilution of antimicrobial oil droplets in the aqueous continuous phase.

  13. Structure-activity relationships and molecular docking of thirteen synthesized flavonoids as horseradish peroxidase inhibitors.

    Science.gov (United States)

    Mahfoudi, Reguia; Djeridane, Amar; Benarous, Khedidja; Gaydou, Emile M; Yousfi, Mohamed

    2017-10-01

    For the first time, the structure-activity relationships of thirteen synthesized flavonoids have been investigated by evaluating their ability to modulate horseradish peroxidase (HRP) catalytic activity. Indeed, a modified spectrophotometrically method was carried out and optimized using 4-methylcatechol (4-MC) as peroxidase co-substrate. The results show that these flavonoids exhibit a great capacity to inhibit peroxidase with Ki values ranged from 0.14±0.01 to 65±0.04mM. Molecular docking has been achieved using Auto Dock Vina program to discuss the nature of interactions and the mechanism of inhibition. According to the docking results, all the flavonoids have shown great binding affinity to peroxidase. These molecular modeling studies suggested that pyran-4-one cycle acts as an inhibition key for peroxidase. Therefore, potent peroxidase inhibitors are flavonoids with these structural requirements: the presence of the hydroxyl (OH) group in 7, 5 and 4' positions and the absence of the methoxy (O-CH 3 ) group. Apigenin contributed better in HRP inhibitory activity. The present study has shown that the studied flavonoids could be promising HRP inhibitors, which can help in developing new molecules to control thyroid diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Red Wine Tannin Structure-Activity Relationships during Fermentation and Maceration.

    Science.gov (United States)

    Yacco, Ralph S; Watrelot, Aude A; Kennedy, James A

    2016-02-03

    The correlation between tannin structure and corresponding activity was investigated by measuring the thermodynamics of interaction between tannins isolated from commercial red wine fermentations and a polystyrene divinylbenzene HPLC column. Must and/or wine samples were collected throughout fermentation/maceration from five Napa Valley wineries. By varying winery, fruit source, maceration time, and cap management practice, it was considered that a reasonably large variation in commercially relevant tannin structure would result. Tannins were isolated from samples collected using low pressure chromatography and were then characterized by gel permeation chromatography and acid-catalyzed cleavage in the presence of excess phloroglucinol (phloroglucinolysis). Corresponding tannin activity was determined using HPLC by measuring the thermodynamics of interaction between isolated tannin and a polystyrene divinylbenzene HPLC column. This measurement approach was designed to determine the ability of tannins to hydrophobically interact with a hydrophobic surface. The results of this study indicate that tannin activity is primarily driven by molecular size. Compositionally, tannin activity was positively associated with seed tannins and negatively associated with skin and pigmented tannins. Although measured indirectly, the extent of tannin oxidation as determined by phloroglucinolysis conversion yield suggests that tannin oxidation at this stage of production reduces tannin activity. Based upon maceration time, this study indicates that observed increases in perceived astringency quality, if related to tannin chemistry, are driven by tannin molecular mass as opposed to pigmented tannin formation or oxidation. Overall, the results of this study give new insight into tannin structure-activity relationships which dominate during extraction.

  15. The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity

    Science.gov (United States)

    Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

    2015-01-01

    In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. PMID:26712768

  16. Deciphering structure-activity relationships in a series of Tat/TAR inhibitors.

    Science.gov (United States)

    Pascale, Lise; González, Alejandro López; Di Giorgio, Audrey; Gaysinski, Marc; Teixido Closa, Jordi; Tejedor, Roger Estrada; Azoulay, Stéphane; Patino, Nadia

    2016-11-01

    A series of pentameric "Polyamide Amino Acids" (PAAs) compounds derived from the same trimeric precursor have been synthesized and investigated as HIV TAR RNA ligands, in the absence and in the presence of a Tat fragment. All PAAs bind TAR with similar sub-micromolar affinities but their ability to compete efficiently with the Tat fragment strongly differs, IC50 ranging from 35 nM to >2 μM. While NMR and CD studies reveal that all PAA interact with TAR at the same site and induce globally the same RNA conformational change upon binding, a comparative thermodynamic study of PAA/TAR equilibria highlights distinct TAR binding modes for Tat competitor and non-competitor PAAs. This led us to suggest two distinct interaction modes that have been further validated by molecular modeling studies. While the binding of Tat competitor PAAs induces a contraction at the TAR bulge region, the binding of non-competitor ones widens it. This could account for the distinct PAA ability to compete with Tat fragment. Our work illustrates how comparative thermodynamic studies of a series of RNA ligands of same chemical family are of value for understanding their binding modes and for rationalizing structure-activity relationships.

  17. Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship.

    Science.gov (United States)

    Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

    2008-05-15

    Several classes of flavonoids [flavanoids (1-10), flavonol (11), isoflavones (12-18), isoflavanones (19-22), isoflavans (23-26), chalcones (27-30), auronol (31), pterocarpans (32-37), 2-arylbenzofuran (38), and neoflavonoid (39)] and lignans (40-42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080 fibrosarcoma cell lines. Based on the observed results, structure-activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxyflavanone (3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66microM), LLC (IC(50), 9.29microM), A549 (IC(50), 8.63microM), and HT-1080 (IC(50), 7.94microM) cancer cell lines, and mucronulatol (26) against LLC (IC(50), 8.38microM) and A549 (IC(50), 9.9microM) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development.

  18. A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs.

    Science.gov (United States)

    Cunningham, Albert R; Carrasquer, C Alex; Mattison, Donald R

    2009-01-01

    The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  19. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Cunningham AlbertR

    2009-11-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  20. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    Directory of Open Access Journals (Sweden)

    Albert R. Cunningham

    2009-01-01

    Full Text Available The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

  1. Calculation of Quantitative Structure-Activity Relationship Descriptors of Artemisinin Derivatives

    Directory of Open Access Journals (Sweden)

    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.

  2. Synthesis and structure-activity relationships of a series of increasingly hydrophobic cationic steroid lipofection reagents.

    Science.gov (United States)

    Gruneich, Jeffrey A; Diamond, Scott L

    2007-05-01

    The use of cholesterol-based cationic lipids and the ability of glucocorticoids to reduce local inflammatory response to lipoplexes motivated an investigation of structure-activity relationships for cationic steroids. A one-step synthetic scheme using iminothiolane was developed to link spermine to the 21-OH position of steroids via an amidine linkage. Five steroids (cortisol, dexamethasone, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone) with increasing hydrophobicity of the parent steroid (Log P(ster) from 1.51 to 3.01) were conjugated with spermine, formulated with dioleoylphosphatidylethanolamine (DOPE) at DOPE : steroid mole ratios (R) of R = 0.5 to 2, and then complexed with 1 microg enhanced green fluorescent protein (EGFP) plasmid DNA at charge ratios (CR) = 2 to 24 amines per phosphate (0.5 to 6 steroids per phosphate). The resulting 105 different formulations of the cationic steroid series were used to lipofect bovine aortic endothelial cells. Transgene expression data at either 24 or 48 h post-lipofection for all formulations was collapsed onto master curves when plotted against a single empirical dimensionless parameter, the lipofection index (LI) = CR (Log P(liposome))(Log P(ster)/|DeltaLog P|) [R/(R + 1)] where DeltaLog P = Log P(DOPE)- Log P(ster) and Log P(liposome) is a mole-weighted average of the DOPE/cationic steroid liposome hydrophobicity. For 7 lipofection increased linearly with LI (EGFP approximately 0 for LI 29, thus providing a predictive design rule based on Log P of the hydrophobic moiety of the cationic steroid lipid. Copyright (c) 2007 John Wiley & Sons, Ltd.

  3. Structure-activity relationship of surfactant for preparing DMFC anodic catalyst

    International Nuclear Information System (INIS)

    Su Yi; Xue Xinzhong; Xu Weilin; Liu Changpeng; Xing Wei; Zhou Xiaochun; Tian Tian; Lu Tianhong

    2006-01-01

    Three kinds of surfactants as stabilizer were applied to the preparation of electrocatalysts for direct methanol fuel cell (DMFC). The catalysts have been characterized by examining their catalytic activities, morphologies and particle sizes by means of cyclic voltammetry, chronoamperometry, X-ray diffraction and transmission electron microscopy (TEM). It is found that the surfactants with different structures have a significantly influence on the catalyst shape and activity. The catalysts prepared with non-ionic surfactants as the stabilizer show higher activity for direct oxidation of methanol. The structure-activity relationship (SAR) analysis has been explored and the effect of hydrophile-lipophile balance (HLB value) has also been discussed

  4. Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

    Science.gov (United States)

    Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

    2014-12-15

    Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Study of the structure-activity relationships of parabens: a practical class

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Joao Paulo dos Santos; Savino, Giovanna; Amarante, Andre Cortinas Goncalves, E-mail: joao.fernandes@mackenzie.br [Centro de Ciencias Biologicas e da Saude, Universidade Presbiteriana Mackenzie, Sao Paulo, SP (Brazil); Sousa, Milena Rodrigues de; Silva, Geane Ramos da [Universidade Camilo Castelo Branco, Sao Paulo, SP (Brazil); Cianciulli, Maria Eliza [Universidade do Grande ABC, Santo Andre, SP (Brazil); Correa, Michelle Fidelis; Ferrarini, Marcio [Centro Universitario Sao Camilo, Sao Paulo, SP (Brazil)

    2013-09-01

    Parabens are p-hydroxybenzoic acid esters widely used as preservatives. With the aim of teaching the structure-activity relationships (SAR) knowledge in a practical form, this paper proposed a practical class to view the SAR of parabens as antimicrobial agents. Methyl, ethyl, n-propyl, isopropyl and isopentyl paraben compounds were synthesized and their respective antimicrobial activities were assessed through determination of minimum inhibitory concentrations (MIC) against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 stains. With the MIC values, it was possible to verify their correlation with calculated lipophilicity (ClogP). This method can be applied in practical Medicinal Chemistry classes. (author)

  6. Quantitative Structure activity relationship and risk analysis of some pesticides in the cattle milk

    OpenAIRE

    Faqir Muhammad*, Ijaz Javed, Masood Akhtar1, Zia-ur-Rahman, Mian Muhammad Awais1, Muhammad Kashif Saleemi2 and Muhammad Irfan Anwar3

    2012-01-01

    Milk of cattle was collected from various localities of Faisalabad, Pakistan. Pesticides concentration was determined by HPLC using solid phase microextraction. The residue analysis revealed that about 40% milk samples were contaminated with pesticides. The mean±SE levels (ppm) of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.38±0.02, 0.26±0.02, 0.072±0.01 and 0.085±0.02, respectively. Quantitative structure activity relationship (QSAR) models were used to predict the residues...

  7. Study of the structure-activity relationships of parabens: a practical class

    International Nuclear Information System (INIS)

    Fernandes, João Paulo dos Santos; Savino, Giovanna; Amarante, André Cortinas Gonçalves; Sousa, Milena Rodrigues de; Silva, Geane Ramos da; Cianciulli, Maria Eliza; Corrêa, Michelle Fidelis; Ferrarini, Márcio

    2013-01-01

    Parabens are p-hydroxybenzoic acid esters widely used as preservatives. With the aim of teaching the structure-activity relationships (SAR) knowledge in a practical form, this paper proposed a practical class to view the SAR of parabens as antimicrobial agents. Methyl, ethyl, n-propyl, isopropyl and isopentyl paraben compounds were synthesized and their respective antimicrobial activities were assessed through determination of minimum inhibitory concentrations (MIC) against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 stains. With the MIC values, it was possible to verify their correlation with calculated lipophilicity (ClogP). This method can be applied in practical Medicinal Chemistry classes. (author)

  8. Structure-Activity Relationships of Pentacyclic Triterpenoids as Potent and Selective Inhibitors against Human Carboxylesterase 1

    Directory of Open Access Journals (Sweden)

    Li-Wei Zou

    2017-06-01

    Full Text Available Human carboxylesterase 1 (hCE1, one of the most important serine hydrolases distributed in liver and adipocytes, plays key roles in endobiotic homeostasis and xenobiotic metabolism. This study aimed to find potent and selective inhibitors against hCE1 from phytochemicals and their derivatives. To this end, a series of natural triterpenoids were collected and their inhibitory effects against human carboxylesterases (hCEs were assayed using D-Luciferin methyl ester (DME and 6,8-dichloro-9,9-dimethyl-7-oxo-7,9-dihydroacridin-2-yl benzoate (DDAB as specific optical substrate for hCE1, and hCE2, respectively. Following screening of a series of natural triterpenoids, oleanolic acid (OA, and ursolic acid (UA were found with strong inhibitory effects on hCE1 and relative high selectivity over hCE2. In order to get the highly selective and potent inhibitors of hCE1, a series of OA and UA derivatives were synthesized from OA and UA by chemical modifications including oxidation, reduction, esterification, and amidation. The inhibitory effects of these derivatives on hCEs were assayed and the structure-activity relationships of tested triterpenoids as hCE1 inhibitors were carefully investigated. The results demonstrated that the carbonyl group at the C-28 site is essential for hCE1 inhibition, the modifications of OA or UA at this site including esters, amides and alcohols are unbeneficial for hCE1 inhibition. In contrast, the structural modifications on OA and UA at other sites, such as converting the C-3 hydroxy group to 3-O-β-carboxypropionyl (compounds 20 and 22, led to a dramatically increase of the inhibitory effects against hCE1 and very high selectivity over hCE2. 3D-QSAR analysis of all tested triterpenoids including OA and UA derivatives provide new insights into the fine relationships linking between the inhibitory effects on hCE1 and the steric-electrostatic properties of triterpenoids. Furthermore, both inhibition kinetic analyses and docking

  9. Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

    Directory of Open Access Journals (Sweden)

    Emmy Tuenter

    2017-02-01

    Full Text Available Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship models were developed, using PLS (partial least squares regression and MLR (multiple linear regression. On the one hand, these models allow for the indication of the most important descriptors (molecular properties responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study.

  10. Structure-activity relationships between sterols and their thermal stability in oil matrix.

    Science.gov (United States)

    Hu, Yinzhou; Xu, Junli; Huang, Weisu; Zhao, Yajing; Li, Maiquan; Wang, Mengmeng; Zheng, Lufei; Lu, Baiyi

    2018-08-30

    Structure-activity relationships between 20 sterols and their thermal stabilities were studied in a model oil system. All sterol degradations were found to be consistent with a first-order kinetic model with determination of coefficient (R 2 ) higher than 0.9444. The number of double bonds in the sterol structure was negatively correlated with the thermal stability of sterol, whereas the length of the branch chain was positively correlated with the thermal stability of sterol. A quantitative structure-activity relationship (QSAR) model to predict thermal stability of sterol was developed by using partial least squares regression (PLSR) combined with genetic algorithm (GA). A regression model was built with R 2 of 0.806. Almost all sterol degradation constants can be predicted accurately with R 2 of cross-validation equals to 0.680. Four important variables were selected in optimal QSAR model and the selected variables were observed to be related with information indices, RDF descriptors, and 3D-MoRSE descriptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Biosynthesis and structure-activity relationships of the lipid a family of glycolipids.

    Science.gov (United States)

    Xiao, Xirui; Sankaranarayanan, Karthik; Khosla, Chaitan

    2017-10-01

    Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the amphipathic glycolipid moiety of LPS. It stimulates the immune system by tightly binding to Toll-like receptor 4. More recently, Lipid A has also been shown to activate intracellular caspase-4 and caspase-5. An impressive diversity is observed in Lipid A structures from different Gram-negative bacteria, and it is well established that subtle changes in chemical structure can result in dramatically different immune activities. For example, Lipid A from Escherichia coli is highly toxic to humans, whereas a biosynthetic precursor called Lipid IV A blocks this toxic activity, and monophosphoryl Lipid A from Salmonella minnesota is a vaccine adjuvant. Thus, an understanding of structure-activity relationships in this glycolipid family could be used to design useful immunomodulatory agents. Here we review the biosynthesis, modification, and structure-activity relationships of Lipid A. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The effect of leverage and/or influential on structure-activity relationships.

    Science.gov (United States)

    Bolboacă, Sorana D; Jäntschi, Lorentz

    2013-05-01

    In the spirit of reporting valid and reliable Quantitative Structure-Activity Relationship (QSAR) models, the aim of our research was to assess how the leverage (analysis with Hat matrix, h(i)) and the influential (analysis with Cook's distance, D(i)) of QSAR models may reflect the models reliability and their characteristics. The datasets included in this research were collected from previously published papers. Seven datasets which accomplished the imposed inclusion criteria were analyzed. Three models were obtained for each dataset (full-model, h(i)-model and D(i)-model) and several statistical validation criteria were applied to the models. In 5 out of 7 sets the correlation coefficient increased when compounds with either h(i) or D(i) higher than the threshold were removed. Withdrawn compounds varied from 2 to 4 for h(i)-models and from 1 to 13 for D(i)-models. Validation statistics showed that D(i)-models possess systematically better agreement than both full-models and h(i)-models. Removal of influential compounds from training set significantly improves the model and is recommended to be conducted in the process of quantitative structure-activity relationships developing. Cook's distance approach should be combined with hat matrix analysis in order to identify the compounds candidates for removal.

  13. Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants

    NARCIS (Netherlands)

    Harju, M.; Hamers, T.; Kamstra, J.H.; Sonneveld, E.; Boon, J.P.

    2007-01-01

    In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs),

  14. Quantitative Structure Activity Relationship of Cinnamaldehyde Compounds against Wood-Decaying Fungi

    Directory of Open Access Journals (Sweden)

    Dongmei Yang

    2016-11-01

    Full Text Available Cinnamaldehyde, of the genius Cinnamomum, is a major constituent of the bark of the cinnamon tree and possesses broad-spectrum antimicrobial activity. In this study, we used best multiple linear regression (BMLR to develop quantitative structure activity relationship (QSAR models for cinnamaldehyde derivatives against wood-decaying fungi Trametes versicolor and Gloeophyllun trabeum. Based on the two optimal QSAR models, we then designed and synthesized two novel cinnamaldehyde compounds. The QSAR models exhibited good correlation coefficients: R2Tv = 0.910 for Trametes versicolor and R2Gt = 0.926 for Gloeophyllun trabeum. Small errors between the experimental and calculated values of two designed compounds indicated that these two QSAR models have strong predictability and stability.

  15. Benzazepines: Structure-activity relationships between D1 receptor blockade and selected pharmacological effects

    International Nuclear Information System (INIS)

    Iorio, L.C.; Billiard, W.; Gold, E.H.

    1986-01-01

    This chapter describes the displacement of 3 H-23390 and 3 H-spiperone binding by dopamine agonists and antagonists. The authors undertook an evaluation of the ability of selected analogs of SCH 23390 to displace 3 H-SCH 23390 and 3 H-spiperone. Structure-activity relationships of SCH 23390 analogs: 7-position substituents, is shown. It is shown that, in general, benzazepines with a variety of substituents in the 7-position retain their selectivity for D 1 sites. Substituents at the 8-position and at the N-position are also discussed. The authors determine a correlation between displacement of 3 H-SCH 23390 and blockade of dopamine-sensitive adenylate cyclase (DSAC). These effects and inhibition of conditioned avoidance responsing (CAS) in rats was also studied. A detailed evaluation is presented of the effects of SCH 23390 and haloperidol in the Inclined Screen and CAR tests

  16. Structure-activity relationships of diverse xanthones against multidrug resistant human tumor cells.

    Science.gov (United States)

    Wang, Qiwen; Ma, Chenyao; Ma, Yun; Li, Xiang; Chen, Yong; Chen, Jianwei

    2017-02-01

    Thirteen xanthones were isolated naturally from the stem of Securidaca inappendiculata Hassk, and structure-activity relationships (SARs) of these compounds were comparatively predicted for their cytotoxic activity against three human multidrug resistant (MDR) cell lines MCF-7/ADR, SMMC-7721/Taxol, and A549/Taxol cells. The results showed that the selected xanthones exhibited different potent cytotoxic activity against the growth of different human tumor cell lines, and most of the xanthones exhibited selective cytotoxicity against SMMC-7721/Taxol cells. Furthermore, some tested xanthones showed stronger cytotoxicity than Cisplatin, which has been used in clinical application extensively. The SARs analysis revealed that the cytotoxic activities of diverse xanthones were affected mostly by the number and position of methoxyl and hydroxyl groups. Xanthones with more free hydroxyl and methoxyl groups increased the cytotoxic activity significantly, especially for those with the presence of C-3 hydroxyl and C-4 methoxyl groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

    2018-03-01

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

  18. Structure modification and functionality of whey proteins: quantitative structure-activity relationship approach.

    Science.gov (United States)

    Nakai, S; Li-Chan, E

    1985-10-01

    According to the original idea of quantitative structure-activity relationship, electric, hydrophobic, and structural parameters should be taken into consideration for elucidating functionality. Changes in these parameters are reflected in the property of protein solubility upon modification of whey proteins by heating. Although solubility is itself a functional property, it has been utilized to explain other functionalities of proteins. However, better correlations were obtained when hydrophobic parameters of the proteins were used in conjunction with solubility. Various treatments reported in the literature were applied to whey protein concentrate in an attempt to obtain whipping and gelling properties similar to those of egg white. Mapping simplex optimization was used to search for the best results. Improvement in whipping properties by pepsin hydrolysis may have been due to higher protein solubility, and good gelling properties resulting from polyphosphate treatment may have been due to an increase in exposable hydrophobicity. However, the results of angel food cake making were still unsatisfactory.

  19. Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

    Science.gov (United States)

    Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

    2006-11-01

    In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.

  20. 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.

  1. Antimalarial benzoheterocyclic 4-aminoquinolines: Structure-activity relationship, in vivo evaluation, mechanistic and bioactivation studies.

    Science.gov (United States)

    Ongarora, Dennis S B; Strydom, Natasha; Wicht, Kathryn; Njoroge, Mathew; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Jurva, Ulrik; Masimirembwa, Collen M; Chibale, Kelly

    2015-09-01

    A novel class of benzoheterocyclic analogues of amodiaquine designed to avoid toxic reactive metabolite formation was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant) and NF54 (sensitive) strains of the malaria parasite Plasmodium falciparum. Structure-activity relationship studies led to the identification of highly promising analogues, the most potent of which had IC50s in the nanomolar range against both strains. The compounds further demonstrated good in vitro microsomal metabolic stability while those subjected to in vivo pharmacokinetic studies had desirable pharmacokinetic profiles. In vivo antimalarial efficacy in Plasmodium berghei infected mice was evaluated for four compounds, all of which showed good activity following oral administration. In particular, compound 19 completely cured treated mice at a low multiple dose of 4×10mg/kg. Mechanistic and bioactivation studies suggest hemozoin formation inhibition and a low likelihood of forming quinone-imine reactive metabolites, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. QUANTITATIVE ELECTRONIC STRUCTURE - ACTIVITY RELATIONSHIP OF ANTIMALARIAL COMPOUND OF ARTEMISININ DERIVATIVES USING PRINCIPAL COMPONENT REGRESSION APPROACH

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    Paul Robert Martin Werfette

    2010-06-01

    Full Text Available Analysis of quantitative structure - activity relationship (QSAR for a series of antimalarial compound artemisinin derivatives has been done using principal component regression. The descriptors for QSAR study were representation of electronic structure i.e. atomic net charges of the artemisinin skeleton calculated by AM1 semi-empirical method. The antimalarial activity of the compound was expressed in log 1/IC50 which is an experimental data. The main purpose of the principal component analysis approach is to transform a large data set of atomic net charges to simplify into a data set which known as latent variables. The best QSAR equation to analyze of log 1/IC50 can be obtained from the regression method as a linear function of several latent variables i.e. x1, x2, x3, x4 and x5. The best QSAR model is expressed in the following equation,  (;;   Keywords: QSAR, antimalarial, artemisinin, principal component regression

  3. Applications of genetic algorithms on the structure-activity relationship analysis of some cinnamamides.

    Science.gov (United States)

    Hou, T J; Wang, J M; Liao, N; Xu, X J

    1999-01-01

    Quantitative structure-activity relationships (QSARs) for 35 cinnamamides were studied. By using a genetic algorithm (GA), a group of multiple regression models with high fitness scores was generated. From the statistical analyses of the descriptors used in the evolution procedure, the principal features affecting the anticonvulsant activity were found. The significant descriptors include the partition coefficient, the molar refraction, the Hammet sigma constant of the substituents on the benzene ring, and the formation energy of the molecules. It could be found that the steric complementarity and the hydrophobic interaction between the inhibitors and the receptor were very important to the biological activity, while the contribution of the electronic effect was not so obvious. Moreover, by construction of the spline models for these four principal descriptors, the effective range for each descriptor was identified.

  4. Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues.

    Science.gov (United States)

    Van Baelen, Gitte; Hostyn, Steven; Dhooghe, Liene; Tapolcsányi, Pál; Mátyus, Péter; Lemière, Guy; Dommisse, Roger; Kaiser, Marcel; Brun, Reto; Cos, Paul; Maes, Louis; Hajós, György; Riedl, Zsuzsanna; Nagy, Ildikó; Maes, Bert U W; Pieters, Luc

    2009-10-15

    Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-beta-carboline, showed the best in vitro activity, with an IC(50) value of 0.45 microM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI>1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure-activity relationships are discussed and compared with related naturally occurring compounds.

  5. Scalable total synthesis and comprehensive structure-activity relationship studies of the phytotoxin coronatine.

    Science.gov (United States)

    Littleson, Mairi M; Baker, Christopher M; Dalençon, Anne J; Frye, Elizabeth C; Jamieson, Craig; Kennedy, Alan R; Ling, Kenneth B; McLachlan, Matthew M; Montgomery, Mark G; Russell, Claire J; Watson, Allan J B

    2018-03-16

    Natural phytotoxins are valuable starting points for agrochemical design. Acting as a jasmonate agonist, coronatine represents an attractive herbicidal lead with novel mode of action, and has been an important synthetic target for agrochemical development. However, both restricted access to quantities of coronatine and a lack of a suitably scalable and flexible synthetic approach to its constituent natural product components, coronafacic and coronamic acids, has frustrated development of this target. Here, we report gram-scale production of coronafacic acid that allows a comprehensive structure-activity relationship study of this target. Biological assessment of a >120 member library combined with computational studies have revealed the key determinants of potency, rationalising hypotheses held for decades, and allowing future rational design of new herbicidal leads based on this template.

  6. Molecular Descriptors Family on Structure Activity Relationships 3. Antituberculotic Activity of some Polyhydroxyxanthones

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    Sorana BOLBOACĂ

    2005-06-01

    Full Text Available The antituberculotic activity of some polyhydroxyxanthones was estimated using the Molecular Descriptors Family on Structure Activity Relationships methodology. From a total number of 298110 real and distinct calculated descriptors, 94843 were significantly different and entered into multiple linear regression analysis. The best performing bi-varied model was obtained by use of all polyhydroxyxanthones. The MDF SAR model was validated splitting the molecules into training and test sets. A correlated correlations analysis was applied in other to compare the MDF SAR models with the previous SAR model. The prediction ability of antituberculotic activity of polyhydroxyxanthones with MDF SAR methodology is sustained by three arguments: leave-one-out procedure, training vs. test procedure, and the correlated correlations analysis. Looking at the bi-varied MDF SAR model, we can conclude that the antituberculotic activity of polyhydroxyxanthones is almost of geometrical nature (99% and is strongly dependent on partial atomic charge and group electronegativity.

  7. STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF DITERPENES FOR TREATMENT OF ALZHEIMER'S DISEASE

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    Gabriel F. dos Santos

    Full Text Available Alzheimer's disease is an irreversible, degenerative and age-related disease which is growing more and more with the increase in life expectancy. Kaurane diterpenes are a class of natural products available in large amounts in nature and isolated from plants grown worldwide. In the present work¸ twenty-seven kaurane diterpenes of natural origin and some readily available derivatives were assayed for acetylcholinesterase inhibition and the structure-activity relationship was analyzed. The kaurenoic acid derivatives screened showed to be promising inhibitors of AChE, which could provide new leads for drugs to fight Alzheimer's disease symptoms. Among them, eleven compounds showed activities comparable or higher than the positive control galantamine. Existence of an allylic hydroxyl group showed to be an important structural feature for AChE inhibition. In addition, presence of free hydroxyl groups at C-17 and C-19, furnished a diol especially active, able to completely inhibit AChE.

  8. Fragment-based quantitative structure-activity relationship (FB-QSAR) for fragment-based drug design.

    Science.gov (United States)

    Du, Qi-Shi; Huang, Ri-Bo; Wei, Yu-Tuo; Pang, Zong-Wen; Du, Li-Qin; Chou, Kuo-Chen

    2009-01-30

    In cooperation with the fragment-based design a new drug design method, the so-called "fragment-based quantitative structure-activity relationship" (FB-QSAR) is proposed. The essence of the new method is that the molecular framework in a family of drug candidates are divided into several fragments according to their substitutes being investigated. The bioactivities of molecules are correlated with the physicochemical properties of the molecular fragments through two sets of coefficients in the linear free energy equations. One coefficient set is for the physicochemical properties and the other for the weight factors of the molecular fragments. Meanwhile, an iterative double least square (IDLS) technique is developed to solve the two sets of coefficients in a training data set alternately and iteratively. The IDLS technique is a feedback procedure with machine learning ability. The standard Two-dimensional quantitative structure-activity relationship (2D-QSAR) is a special case, in the FB-QSAR, when the whole molecule is treated as one entity. The FB-QSAR approach can remarkably enhance the predictive power and provide more structural insights into rational drug design. As an example, the FB-QSAR is applied to build a predictive model of neuraminidase inhibitors for drug development against H5N1 influenza virus. (c) 2008 Wiley Periodicals, Inc.

  9. Structure-activity relationships for novel drug precursor N-substituted-6-acylbenzothiazolon derivatives: A theoretical approach

    Science.gov (United States)

    Sıdır, Yadigar Gülseven; Sıdır, İsa

    2013-08-01

    In this study, the twelve new modeled N-substituted-6-acylbenzothiazolon derivatives having analgesic analog structure have been investigated by quantum chemical methods using a lot of electronic parameters and structure-activity properties; such as molecular polarizability (α), dipole moment (μ), EHOMO, ELUMO, q-, qH+, molecular volume (Vm), ionization potential (IP), electron affinity (EA), electronegativity (χ), molecular hardness (η), molecular softness (S), electrophilic index (ω), heat of formation (HOF), molar refractivity (MR), octanol-water partition coefficient (log P), thermochemical properties (entropy (S), capacity of heat (Cv)); as to investigate activity relationships with molecular structure. The correlations of log P with Vm, MR, ω, EA, EHOMO - ELUMO (ΔE), HOF in aqueous phase, χ, μ, S, η parameters, respectively are obtained, while the linear relation of log P with IP, Cv, HOF in gas phase are not observed. The log P parameter is obtained to be depending on different properties of compounds due to their complexity.

  10. A Quantitative Structure-Activity Relationships (QSAR Study of Piperine Based Derivatives with Leishmanicidal Activity

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    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

  11. Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors.

    Science.gov (United States)

    Nargotra, Amit; Sharma, Sujata; Koul, Jawahir Lal; Sangwan, Pyare Lal; Khan, Inshad Ali; Kumar, Ashwani; Taneja, Subhash Chander; Koul, Surrinder

    2009-10-01

    Quantitative structure activity relationship (QSAR) analysis of piperine analogs as inhibitors of efflux pump NorA from Staphylococcus aureus has been performed in order to obtain a highly accurate model enabling prediction of inhibition of S. aureus NorA of new chemical entities from natural sources as well as synthetic ones. Algorithm based on genetic function approximation method of variable selection in Cerius2 was used to generate the model. Among several types of descriptors viz., topological, spatial, thermodynamic, information content and E-state indices that were considered in generating the QSAR model, three descriptors such as partial negative surface area of the compounds, area of the molecular shadow in the XZ plane and heat of formation of the molecules resulted in a statistically significant model with r(2)=0.962 and cross-validation parameter q(2)=0.917. The validation of the QSAR models was done by cross-validation, leave-25%-out and external test set prediction. The theoretical approach indicates that the increase in the exposed partial negative surface area increases the inhibitory activity of the compound against NorA whereas the area of the molecular shadow in the XZ plane is inversely proportional to the inhibitory activity. This model also explains the relationship of the heat of formation of the compound with the inhibitory activity. The model is not only able to predict the activity of new compounds but also explains the important regions in the molecules in quantitative manner.

  12. Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

    Science.gov (United States)

    Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

    2008-01-01

    Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

  13. Quantitative structure-activity relationship (QSAR) for insecticides: development of predictive in vivo insecticide activity models.

    Science.gov (United States)

    Naik, P K; Singh, T; Singh, H

    2009-07-01

    Quantitative structure-activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r(2) values of 0.949 and 0.838 as well as [image omitted] values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD(50) values for the test set data with r(2) of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.

  14. Anticancer and reversing multidrug resistance activities of natural isoquinoline alkaloids and their structure-activity relationship.

    Science.gov (United States)

    Qing, Zhi-Xing; Huang, Jia-Lu; Yang, Xue-Yi; Liu, Jing-Hong; Cao, Hua-Liang; Xiang, Feng; Cheng, Pi; Zeng, Jian-Guo

    2017-09-20

    The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloid (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Flavonoids as Vasorelaxant Agents: Synthesis, Biological Evaluation and Quantitative Structure Activities Relationship (QSAR Studies

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    Yongzhou Hu

    2011-09-01

    Full Text Available A series of 2-(2-diethylamino-ethoxychalcone and 6-prenyl(or its isomers-flavanones 10a,b and 11a–g were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pretreated with 1 μM phenylephrine (PE. Several compounds showed potent vasorelaxant activities. Compound 10a (EC50 = 7.6 μM, Emax = 93.1%, the most potent one, would be a promising structural template for development of novel and more efficient vasodilators. Further, 2D-QSAR analysis of compounds 10a,b and 11c-e as well as thirty previously synthesized flavonoids 1-3 and 12-38 using Enhanced Replacement Method-Multiple Linear Regression (ERM-MLR was further performed based on an optimal set of molecular descriptors (H5m, SIC2, DISPe, Mor03u and L3m, leading to a reliable model with good predictive ability (Rtrain2 = 0.839, Qloo2 = 0.733 and Rtest2 = 0.804. The results provide good insights into the structure- activity relationships of the target compounds.

  16. Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

    Science.gov (United States)

    Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

    2006-06-01

    The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

  17. The uridine diphosphate glucuronosyltransferases: quantitative structure-activity relationships for hydroxyl polychlorinated biphenyl substrates

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Degao [Dalian University of Technology, Department of Environmental Science and Technology, Dalian (China)

    2005-10-01

    Quantitative structure-activity relationships (QSARs), which relate the glucuronidation of hydroxyl polychlorinated biphenyls (OH-PCBs) - catalyzed by the uridine diphosphate glucuronosyltransferases (UGTs) - to their physicochemical properties and molecular structural parameters, can be used to predict the rate constants and interpret the mechanism of glucuronidation. In this study, QSARs have been developed that use 23 semi-empirical calculated quantum chemical descriptors to predict the logarithms of the constants 1/K{sub m} and V{sub max}, related to enzyme kinetics. A partial least squares regression method was used to select the optimal set of descriptors to minimize the multicollinearity between the descriptors, as well as to maximize the cross-validated coefficient (Q{sup 2} {sub cum}) values. The key descriptors affecting log(1/K{sub m}) were E{sub lumo}- E{sub homo} (the energy gap between the lowest unoccupied molecular orbital and the highest occupied molecular orbital) and q{sub C}{sup -} (the largest negative net atomic charge on a carbon atom), while the key descriptors affecting log V{sub max} were the polarizability {alpha}, the Connolly solvent-excluded volume (CSEV), and logP (the logarithm of the partition coefficient for octanol/water). From the results obtained it can be concluded that hydrophobic and electronic aspects of OH-PCBs are important in the glucuronidation of OH-PCBs. (orig.)

  18. Quantitative Structure--Activity Relationship (QSAR) for the Oxidation of Trace Organic Contaminants by Sulfate Radical.

    Science.gov (United States)

    Xiao, Ruiyang; Ye, Tiantian; Wei, Zongsu; Luo, Shuang; Yang, Zhihui; Spinney, Richard

    2015-11-17

    The sulfate radical anion (SO4•–) based oxidation of trace organic contaminants (TrOCs) has recently received great attention due to its high reactivity and low selectivity. In this study, a meta-analysis was conducted to better understand the role of functional groups on the reactivity between SO4•– and TrOCs. The results indicate that compounds in which electron transfer and addition channels dominate tend to exhibit a faster second-order rate constants (kSO4•–) than that of H–atom abstraction, corroborating the SO4•– reactivity and mechanisms observed in the individual studies. Then, a quantitative structure activity relationship (QSAR) model was developed using a sequential approach with constitutional, geometrical, electrostatic, and quantum chemical descriptors. Two descriptors, ELUMO and EHOMO energy gap (ELUMO–EHOMO) and the ratio of oxygen atoms to carbon atoms (#O:C), were found to mechanistically and statistically affect kSO4•– to a great extent with the standardized QSAR model: ln kSO4•– = 26.8–3.97 × #O:C – 0.746 × (ELUMO–EHOMO). In addition, the correlation analysis indicates that there is no dominant reaction channel for SO4•– reactions with various structurally diverse compounds. Our QSAR model provides a robust predictive tool for estimating emerging micropollutants removal using SO4•– during wastewater treatment processes.

  19. Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction.

    Science.gov (United States)

    De Filippis, Vincenzo; Acquasaliente, Laura; Pontarollo, Giulia; Peterle, Daniele

    2018-01-01

    The advent of recombinant DNA technology allowed to site-specifically insert, delete, or mutate almost any amino acid in a given protein, significantly improving our knowledge of protein structure, stability, and function. Nevertheless, a quantitative description of the physical and chemical basis that makes a polypeptide chain to efficiently fold into a stable and functionally active conformation is still elusive. This mainly originates from the fact that nature combined, in a yet unknown manner, different properties (i.e., hydrophobicity, conformational propensity, polarizability, and hydrogen bonding capability) into the 20 standard natural amino acids, thus making difficult, if not impossible, to univocally relate the change in protein stability or function to the alteration of physicochemical properties caused by amino acid exchange(s). In this view, incorporation of noncoded amino acids with tailored side chains, allowing to finely tune the structure at a protein site, would facilitate to dissect the effects of a given mutation in terms of one or a few physicochemical properties, thus much expanding the scope of physical organic chemistry in the study of proteins. In this review, relevant applications from our laboratory will be presented on the use of noncoded amino acids in structure-activity relationships studies of hirudin binding to thrombin. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  20. Quantitative Structure activity relationship and risk analysis of some pesticides in the cattle milk

    Directory of Open Access Journals (Sweden)

    Faqir Muhammad*, Ijaz Javed, Masood Akhtar1, Zia-ur-Rahman, Mian Muhammad Awais1, Muhammad Kashif Saleemi2 and Muhammad Irfan Anwar3

    2012-10-01

    Full Text Available Milk of cattle was collected from various localities of Faisalabad, Pakistan. Pesticides concentration was determined by HPLC using solid phase microextraction. The residue analysis revealed that about 40% milk samples were contaminated with pesticides. The mean±SE levels (ppm of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.38±0.02, 0.26±0.02, 0.072±0.01 and 0.085±0.02, respectively. Quantitative structure activity relationship (QSAR models were used to predict the residues of unknown pesticides in the milk of cattle using their known physicochemical properties such as molecular weight (MW, melting point (MP, and log octanol to water partition coefficient (Ko/w as well as the milk characteristics such as pH, % fat, and specific gravity (SG in this species. The analysis revealed good correlation coefficients (R2 = 0.91 for cattle QSAR model. The coefficient for Ko/w for the studied pesticides was higher in cattle milk. Risk analysis was conducted based upon the determined pesticide residues and their provisional tolerable daily intakes. The daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study were 3, 11, 2.5 times higher, respectively in cattle milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

  1. Structure-Activity Relationship Analysis of 3-phenylcoumarin-Based Monoamine Oxidase B Inhibitors

    Science.gov (United States)

    Rauhamäki, Sanna; Postila, Pekka A.; Niinivehmas, Sanna; Kortet, Sami; Schildt, Emmi; Pasanen, Mira; Manivannan, Elangovan; Ahinko, Mira; Koskimies, Pasi; Nyberg, Niina; Huuskonen, Pasi; Multamäki, Elina; Pasanen, Markku; Juvonen, Risto O.; Raunio, Hannu; Huuskonen, Juhani; Pentikäinen, Olli T.

    2018-03-01

    Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson’s disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM - 1 µM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activity relationship analysis summarizes the atom-level determinants of the MAO-B inhibition by the derivatives. Finally, the cross-reactivity of the derivatives was tested against monoamine oxidase A and a specific subset of enzymes linked to estradiol metabolism, known to have coumarin-based inhibitors. Overall, the results indicate that the 3-phenylcoumarins, especially derivative 1, present unique pharmacological features worth considering in future drug development.

  2. Attraction Pheromone of The Benthic Diatom Seminavis robusta: Studies on Structure-Activity Relationships.

    Science.gov (United States)

    Lembke, Christine; Stettin, Daniel; Speck, Franziska; Ueberschaar, Nico; De Decker, Sam; Vyverman, Wim; Pohnert, Georg

    2018-04-01

    Recently the first pheromone of a marine diatom was identified to be the diketopiperazine (S,S)-diproline. This compound facilitates attraction between mating partners in the benthic diatom Seminavis robusta. Interestingly, sexualized S. robusta cells are attracted to both the natural pheromone (S,S)-diproline as well as to its enantiomer (R,R)-diproline. Usually stereospecificity is a prerequisite for successful substrate-receptor interactions, and especially pheromone perception is often highly enantioselective. Here we introduce a structure-activity relationship study, to learn more about the principles of pheromone reception in diatoms. We analyzed the activity of nine different diketopiperazines in attraction and interference assays. The pheromone diproline itself, as well as a pipecolic acid derived diketopiperazine with two expanded aliphatic ring systems, showed the highest attractivity. Hydroxylatoin of the aliphatic rings abolished any bioactivity. Diketopiperazines derived from acyclic amino acids were not attrative as well. All stereoisomers of both the diproline and the pipecolic acid derived diketopiperazine were purified by enantioselective high-performance liquid chromatography, and application in bioactivity tests confirmed that attraction pheromone perception in this diatom is indeed not stereospecific. However, the lack of activity of diketopiperazines derived from acyclic amino acids suggests a specificity that prevents misguidance to sources of other naturally occurring diketopiperazines.

  3. Antiproliferative terpenoids from almond hulls (Prunus dulcis): identification and structure-activity relationships.

    Science.gov (United States)

    Amico, Vincenzo; Barresi, Vincenza; Condorelli, Daniele; Spatafora, Carmela; Tringali, Corrado

    2006-02-08

    Bioassay-guided fractionation of the EtOAc crude extract from Sicilian almond hulls, a waste material from Prunus dulcis crop, allowed identification of 10 constituents, isolated as pure compounds (1-5, 7, and 10) or unseparable mixtures (5 + 6 and 8 + 9). All compounds were subjected to spectroscopic analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide bioassay on MCF-7 human breast cancer cells. In addition to the main components oleanolic (1), ursolic (2), and betulinic (3) acids, the 2-hydroxy analogues alphitolic (4), corosolic (5), and maslinic (6) acids, as well as the related aldehydes, namely, betulinic (7), oleanolic (8), and ursolic (9), were identified. From a more polar fraction, the beta-sitosterol 3-O-glucoside (10) was also identified. A sample of commercially available betulin (11) was also included in bioassays as further support to a structure-activity relationship study. Betulinic acid showed antiproliferative activity toward MCF-7 cells (GI50 = 0.27 microM), higher than the anticancer drug 5-fluorouracil.

  4. Structure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439).

    Science.gov (United States)

    Dong, Yuxiang; Wang, Xiaofang; Kamaraj, Sriraghavan; Bulbule, Vivek J; Chiu, Francis C K; Chollet, Jacques; Dhanasekaran, Manickam; Hein, Christopher D; Papastogiannidis, Petros; Morizzi, Julia; Shackleford, David M; Barker, Helena; Ryan, Eileen; Scheurer, Christian; Tang, Yuanqing; Zhao, Qingjie; Zhou, Lin; White, Karen L; Urwyler, Heinrich; Charman, William N; Matile, Hugues; Wittlin, Sergio; Charman, Susan A; Vennerstrom, Jonathan L

    2017-04-13

    Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pK a and lower log D 7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D 7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

  5. Compound toxicity screening and structure-activity relationship modeling in Escherichia coli.

    Science.gov (United States)

    Planson, Anne-Gaëlle; Carbonell, Pablo; Paillard, Elodie; Pollet, Nicolas; Faulon, Jean-Loup

    2012-03-01

    Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/∼faulon/EcoliTox.php). Copyright © 2011 Wiley Periodicals, Inc.

  6. Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout.

    Science.gov (United States)

    Mendenhall, Jeffrey; Meiler, Jens

    2016-02-01

    Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods.

  7. Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

    Science.gov (United States)

    Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik

    2017-07-01

    After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural diverse polymers which are capable to estimate green algae growth inhibition (EC50). The model (N = 43, R 2  = 0.73, RMSE = 0.28) is a regression-based decision tree using one structural descriptor for each of three polymer classes separated based on charge. The QSAR is applicable to linear homo polymers as well as copolymers and does not require information on the size of the polymer particle or underlying core material. Highly branched polymers, non-nitrogen cationic polymers and polymeric surfactants are not included in the model and thus cannot be evaluated. The model works best for cationic and non-ionic polymers for which cellular adsorption, disruption of the cell wall and photosynthesis inhibition were the mechanisms of action. For anionic polymers, specific properties of the polymer and test characteristics need to be known for detailed assessment. The data and QSAR results for anionic polymers, when combined with molecular dynamics simulations indicated that nutrient depletion is likely the dominant mode of toxicity. Nutrient depletion in turn, is determined by the non-linear interplay between polymer charge density and backbone flexibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 6-Nitrobenzimidazole derivatives: potential phosphodiesterase inhibitors: synthesis and structure-activity relationship.

    Science.gov (United States)

    Khan, K M; Shah, Zarbad; Ahmad, V U; Ambreen, N; Khan, M; Taha, M; Rahim, F; Noreen, S; Perveen, S; Choudhary, M I; Voelter, W

    2012-02-15

    6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC(50) values between 1.5±0.043 and 294.0±16.7 μM. Compounds 30 (IC(50)=1.5±0.043 μM), 1 (IC(50)=2.4±0.049 μM), 11 (IC(50)=5.7±0.113 μM), 13 (IC(50)=6.4±0.148 μM), 14 (IC(50)=10.5±0.51 μM), 9 (IC(50)=11.49±0.08 μM), 3 (IC(50)=63.1±1.48 μM), 10 (IC(50)=120.0±4.47 μM), and 6 (IC(50)=153.2±5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC(50)=274±0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Cytotoxic constituents of propolis from Myanmar and their structure-activity relationship.

    Science.gov (United States)

    Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

    2009-12-01

    Thirteen cycloartane-type tritepenes (1-13) and four prenylated flavanones (14-17) isolated from propolis collected in Myanmar, were evaluated for their cytotoxic activity against a panel of six different cancer cell lines; three murine cancer cell lines (colon 26-L5 carcinoma, B16-BL6 melanoma, and Lewis lung carcinoma) and three human cancer cell lines (lung A549 adenocarcinoma, cervix HeLa adenocarcinoma and HT-1080 fibrosarcoma). Among them, a cycloartane-type triterpene, 3alpha,27-dihydroxycycloart-24E-en-26-oic acid (3), showed the most potent cytotoxicity against B16-BL6 cells with an IC(50) value of 5.91 microM, comparable to those of positive controls, doxorubicin (IC(50), 5.66 microM) and 5-fluorouracil (IC(50), 4.88 microM). In addition, (2S)-5,7-dihydroxy-4'-methoxy-8,3'-diprenylflavanone (14) exhibited strong cytotoxicity against all the tested cancer cell lines with the IC(50) values ranging from 14.0 to 26.4 microM. Based on the observed results, the structure-activity relationships are discussed.

  10. Structure-Activity Relationships for Rates of Aromatic Amine Oxidation by Manganese Dioxide.

    Science.gov (United States)

    Salter-Blanc, Alexandra J; Bylaska, Eric J; Lyon, Molly A; Ness, Stuart C; Tratnyek, Paul G

    2016-05-17

    New energetic compounds are designed to minimize their potential environmental impacts, which includes their transformation and the fate and effects of their transformation products. The nitro groups of energetic compounds are readily reduced to amines, and the resulting aromatic amines are subject to oxidation and coupling reactions. Manganese dioxide (MnO2) is a common environmental oxidant and model system for kinetic studies of aromatic amine oxidation. In this study, a training set of new and previously reported kinetic data for the oxidation of model and energetic-derived aromatic amines was assembled and subjected to correlation analysis against descriptor variables that ranged from general purpose [Hammett σ constants (σ(-)), pKas of the amines, and energies of the highest occupied molecular orbital (EHOMO)] to specific for the likely rate-limiting step [one-electron oxidation potentials (Eox)]. The selection of calculated descriptors (pKa, EHOMO, and Eox) was based on validation with experimental data. All of the correlations gave satisfactory quantitative structure-activity relationships (QSARs), but they improved with the specificity of the descriptor. The scope of correlation analysis was extended beyond MnO2 to include literature data on aromatic amine oxidation by other environmentally relevant oxidants (ozone, chlorine dioxide, and phosphate and carbonate radicals) by correlating relative rate constants (normalized to 4-chloroaniline) to EHOMO (calculated with a modest level of theory).

  11. Structure-Activity Relationships for Rates of Aromatic Amine Oxidation by Manganese Dioxide

    International Nuclear Information System (INIS)

    Salter-Blanc, Alexandra J.; Lyon, Molly A.; Science University, Portland, OR; Ness, Stuart C.; Science University, Portland, OR; Tratnyek, Paul G.; Science University, Portland, OR

    2016-01-01

    New energetic compounds are designed to minimize their potential environmental impacts, which includes their transformation and the fate and effects of their transformation products. The nitro groups of energetic compounds are readily reduced to amines, and the resulting aromatic amines are subject to oxidation and coupling reactions. Manganese dioxide (MnO 2 ) is a common environmental oxidant and model system for kinetic studies of aromatic amine oxidation. Here in this study, a training set of new and previously reported kinetic data for the oxidation of model and energetic-derived aromatic amines was assembled and subjected to correlation analysis against descriptor variables that ranged from general purpose [Hammett σ constants (σ − ), pK a s of the amines, and energies of the highest occupied molecular orbital (E HOMO )] to specific for the likely rate-limiting step [one-electron oxidation potentials (E ox )]. The selection of calculated descriptors (pK a ), E HOMO , and E ox ) was based on validation with experimental data. All of the correlations gave satisfactory quantitative structure-activity relationships (QSARs), but they improved with the specificity of the descriptor. The scope of correlation analysis was extended beyond MnO 2 to include literature data on aromatic amine oxidation by other environmentally relevant oxidants (ozone, chlorine dioxide, and phosphate and carbonate radicals) by correlating relative rate constants (normalized to 4-chloroaniline) to E HOMO (calculated with a modest level of theory).

  12. Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

    Science.gov (United States)

    Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

    1998-01-15

    We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

  13. Deep neural nets as a method for quantitative structure-activity relationships.

    Science.gov (United States)

    Ma, Junshui; Sheridan, Robert P; Liaw, Andy; Dahl, George E; Svetnik, Vladimir

    2015-02-23

    Neural networks were widely used for quantitative structure-activity relationships (QSAR) in the 1990s. Because of various practical issues (e.g., slow on large problems, difficult to train, prone to overfitting, etc.), they were superseded by more robust methods like support vector machine (SVM) and random forest (RF), which arose in the early 2000s. The last 10 years has witnessed a revival of neural networks in the machine learning community thanks to new methods for preventing overfitting, more efficient training algorithms, and advancements in computer hardware. In particular, deep neural nets (DNNs), i.e. neural nets with more than one hidden layer, have found great successes in many applications, such as computer vision and natural language processing. Here we show that DNNs can routinely make better prospective predictions than RF on a set of large diverse QSAR data sets that are taken from Merck's drug discovery effort. The number of adjustable parameters needed for DNNs is fairly large, but our results show that it is not necessary to optimize them for individual data sets, and a single set of recommended parameters can achieve better performance than RF for most of the data sets we studied. The usefulness of the parameters is demonstrated on additional data sets not used in the calibration. Although training DNNs is still computationally intensive, using graphical processing units (GPUs) can make this issue manageable.

  14. Biosynthetically Guided Structure-Activity Relationship Studies of Merochlorin A, an Antibiotic Marine Natural Product.

    Science.gov (United States)

    López-Pérez, Borja; Pepper, Henry P; Ma, Rong; Fawcett, Benjamin J; Pehere, Ashok D; Wei, Qi; Ji, Zengchun; Polyak, Steven W; Dai, Huanqin; Song, Fuhang; Abell, Andrew D; Zhang, Lixin; George, Jonathan H

    2017-12-07

    The onset of new multidrug-resistant strains of bacteria demands continuous development of antibacterial agents with new chemical scaffolds and mechanisms of action. We present the first structure-activity relationship (SAR) study of 16 derivatives of a structurally novel antibiotic merochlorin A that were designed using a biosynthetic blueprint. Our lead compounds are active against several Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are relatively nontoxic to human cell lines. Furthermore, derivative 12 c {(±)-(3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione} was found to inhibit the growth of Bacillus Calmette-Guérin (BCG)-infected cells at concentrations similar to rifampicin. These results outperform the natural product, underscoring the potential of merochlorin analogues as a new class of antibiotics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Structure-Activity Relationships of the Human Immunodeficiency Virus Type 1 Maturation Inhibitor PF-46396.

    Science.gov (United States)

    Murgatroyd, Christopher; Pirrie, Lisa; Tran, Fanny; Smith, Terry K; Westwood, Nicholas J; Adamson, Catherine S

    2016-09-15

    HIV-1 maturation inhibitors are a novel class of antiretroviral compounds that consist of two structurally distinct chemical classes: betulinic acid derivatives and the pyridone-based compound PF-46396. It is currently believed that both classes act by similar modes of action to generate aberrant noninfectious particles via inhibition of CA-SP1 cleavage during Gag proteolytic processing. In this study, we utilized a series of novel analogues with decreasing similarity to PF-46396 to determine the chemical groups within PF-46396 that contribute to antiviral activity, Gag binding, and the relationship between these essential properties. A spectrum of antiviral activity (active, intermediate, and inactive) was observed across the analogue series with respect to CA-SP1 cleavage and HIV-1 (NL4-3) replication kinetics in Jurkat T cells. We demonstrate that selected inactive analogues are incorporated into wild-type (WT) immature particles and that one inactive analogue is capable of interfering with PF-46396 inhibition of CA-SP1 cleavage. Mutations that confer PF-46396 resistance can impose a defective phenotype on HIV-1 that can be rescued in a compound-dependent manner. Some inactive analogues retained the capacity to rescue PF-46396-dependent mutants (SP1-A3V, SP1-A3T, and CA-P157S), implying that they can also interact with mutant Gag. The structure-activity relationships observed in this study demonstrate that (i) the tert-butyl group is essential for antiviral activity but is not an absolute requirement for Gag binding, (ii) the trifluoromethyl group is optimal but not essential for antiviral activity, and (iii) the 2-aminoindan group is important for antiviral activity and Gag binding but is not essential, as its replacement is tolerated. Combinations of antiretroviral drugs successfully treat HIV/AIDS patients; however, drug resistance problems make the development of new mechanistic drug classes an ongoing priority. HIV-1 maturation inhibitors are novel as they

  16. Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity

    International Nuclear Information System (INIS)

    Morales, Aliuska Helguera; Perez, Miguel Angel Cabrera; Combes, Robert D.; Gonzalez, Maykel Perez

    2006-01-01

    Several nitrocompounds have been screened for carcinogenicity in rodents, but this is a lengthy and expensive process, taking two years and typically costing 2.5 million dollars, and uses large numbers of animals. There is, therefore, much impetus to develop suitable alternative methods. One possible way of predicting carcinogenicity is to use quantitative structure-activity relationships (QSARs). QSARs have been widely utilized for toxicity testing, thereby contributing to a reduction in the need for experimental animals. This paper describes the results of applying a TOPological substructural molecular design (TOPS-MODE) approach for predicting the rodent carcinogenicity of nitrocompounds. The model described 79.10% of the experimental variance, with a standard deviation of 0.424. The predictive power of the model was validated by leave-one-out validation, with a determination coefficient of 0.666. In addition, this approach enabled the contribution of different fragments to carcinogenic potency to be assessed, thereby making the relationships between structure and carcinogenicity to be transparent. It was found that the carcinogenic activity of the chemicals analysed was increased by the presence of a primary amine group bonded to the aromatic ring, a manner that was proportional to the ring aromaticity. The nitro group bonded to an aromatic carbon atom is a more important determinant of carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the TOPS-MODE approach was compared with four other predictive models, but none of these could explain more than 66% of the variance in the carcinogenic potency with the same number of variables

  17. Evolution of the international workshops on quantitative structure-activity relationships (QSARs) in environmental toxicology.

    Science.gov (United States)

    Kaiser, K L E

    2007-01-01

    This presentation will review the evolution of the workshops from a scientific and personal perspective. From their modest beginning in 1983, the workshops have developed into larger international meetings, regularly held every two years. Their initial focus on the aquatic sphere soon expanded to include properties and effects on atmospheric and terrestrial species, including man. Concurrent with this broadening of their scientific scope, the workshops have become an important forum for the early dissemination of all aspects of qualitative and quantitative structure-activity research in ecotoxicology and human health effects. Over the last few decades, the field of quantitative structure/activity relationships (QSARs) has quickly emerged as a major scientific method in understanding the properties and effects of chemicals on the environment and human health. From substances that only affect cell membranes to those that bind strongly to a specific enzyme, QSARs provides insight into the biological effects and chemical and physical properties of substances. QSARs are useful for delineating the quantitative changes in biological effects resulting from minor but systematic variations of the structure of a compound with a specific mode of action. In addition, more holistic approaches are being devised that result in our ability to predict the effects of structurally unrelated compounds with (potentially) different modes of action. Research in QSAR environmental toxicology has led to many improvements in the manufacturing, use, and disposal of chemicals. Furthermore, it has led to national policies and international agreements, from use restrictions or outright bans of compounds, such as polychlorinated biphenyls (PCBs), mirex, and highly chlorinated pesticides (e.g. DDT, dieldrin) for the protection of avian predators, to alternatives for ozone-depleting compounds, to better waste treatment systems, to more powerful and specific acting drugs. Most of the recent advances

  18. Quantitative structure activity relationship and risk analysis of some pesticides in the goat milk.

    Science.gov (United States)

    Muhammad, Faqir; Awais, Mian Muhammad; Akhtar, Masood; Anwar, Muhammad Irfan

    2013-01-04

    The detection and quantification of different pesticides in the goat milk samples collected from different localities of Faisalabad, Pakistan was performed by HPLC using solid phase microextraction. The analysis showed that about 50% milk samples were contaminated with pesticides. The mean±SEM levels (ppm) of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.34±0.007, 0.063±0.002, 0.034±0.002 and 0.092±0.002, respectively; whereas, methyl parathion was not detected in any of the analyzed samples. Quantitative structure activity relationship (QSAR) models were suggested to predict the residues of unknown pesticides in the goat milk using their known physicochemical characteristics including molecular weight (MW), melting point (MP), and log octanol to water partition coefficient (Ko/w) in relation to the characteristics such as pH, % fat, specific gravity and refractive index of goat milk. The analysis revealed good correlation coefficient (R2 = 0.985) for goat QSAR model. The coefficients for Ko/w and refractive index for the studied pesticides were higher in goat milk. This suggests that these are better determinants for pesticide residue prediction in the milk of these animals. Based upon the determined pesticide residues and their provisional tolerable daily intakes, risk analysis was also conducted which showed that daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study are 2.68, 5.19 and 2.71 times higher, respectively in the goat milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

  19. Quantitative Structure Activity Relationship and Risk Analysis of Some Pesticides in the Goat milk

    Directory of Open Access Journals (Sweden)

    Faqir Muhammad

    2013-01-01

    Full Text Available The detection and quantification of different pesticides in the goat milk samples collected from different localities of Faisalabad, Pakistan was performed by HPLC using solid phase microextraction. The analysis showed that about 50% milk samples were contaminated with pesticides. The mean+/-SEM levels (ppm of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.34+/-0.007, 0.063+/-0.002, 0.034+/-0.002 and 0.092+/-0.002, respectively; whereas, methyl parathion was not detected in any of the analyzed samples. Quantitative structure activity relationship (QSAR models were suggested to predict the residues of unknown pesticides in the goat milk using their known physicochemical characteristics including molecular weight (MW, melting point (MP, and log octanol to water partition coefficient (Ko/w in relation to the characteristics such as pH, % fat, specific gravity and refractive index of goat milk. The analysis revealed good correlation coefficient (R2 = 0.985 for goat QSAR model. The coefficients for Ko/w and refractive index for the studied pesticides were higher in goat milk. This suggests that these are better determinants for pesticide residue prediction in the milk of these animals. Based upon the determined pesticide residues and their provisional tolerable daily intakes, risk analysis was also conducted which showed that daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study are 2.68, 5.19 and 2.71 times higher, respectively in the goat milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

  20. Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

    Science.gov (United States)

    Carbone, V; Kim, H; Huang, J X; Baker, M A; Ong, C; Cooper, M A; Li, J; Rockman, S; Velkov, T

    2013-01-01

    Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.

  1. Structure Activity Relationships of α-L-LNA Modified Phosphorothioate Gapmer Antisense Oligonucleotides in Animals

    Directory of Open Access Journals (Sweden)

    Punit P Seth

    2012-01-01

    Full Text Available We report the structure activity relationships of short 14-mer phosphorothioate gapmer antisense oligonucleotides (ASOs modified with α-L-locked nucleic acid (LNA and related modifications targeting phosphatase and tensin homologue (PTEN messenger RNA in mice. α-L-LNA represents the α-anomer of enantio-LNA and modified oligonucleotides show LNA like binding affinity for complementary RNA. In contrast to sequence matched LNA gapmer ASOs which showed elevations in plasma alanine aminotransferase (ALT levels indicative of hepatotoxicity, gapmer ASOs modified with α-L-LNA and related analogs in the flanks showed potent downregulation of PTEN messenger RNA in liver tissue without producing elevations in plasma ALT levels. However, the α-L-LNA ASO showed a moderate dose-dependent increase in liver and spleen weights suggesting a higher propensity for immune stimulation. Interestingly, replacing α-L-LNA nucleotides in the 3′- and 5′-flanks with R-5′-Me-α-L-LNA but not R-6′-Me- or 3′-Me-α-L-LNA nucleotides, reversed the drug induced increase in organ weights. Examination of structural models of dinucleotide units suggested that the 5′-Me group increases steric bulk in close proximity to the phosphorothioate backbone or produces subtle changes in the backbone conformation which could interfere with recognition of the ASO by putative immune receptors. Our data suggests that introducing steric bulk at the 5′-position of the sugar-phosphate backbone could be a general strategy to mitigate the immunostimulatory profile of oligonucleotide drugs. In a clinical setting, proinflammatory effects manifest themselves as injection site reactions and flu-like symptoms. Thus, a mitigation of these effects could increase patient comfort and compliance when treated with ASOs.

  2. An automated pulse labelling method for structure-activity relationship studies with antibacterial oxazolidinones.

    Science.gov (United States)

    Eustice, D C; Brittelli, D R; Feldman, P A; Brown, L J; Borkowski, J J; Slee, A M

    1990-01-01

    The 3-aryl-2-oxooxazolidinones are a new class of synthetic antibacterial agents that potently inhibit protein synthesis. An automated pulse labelling method with [3H]-lysine was developed with Bacillus subtilis to obtain additional quantitative activity data for structure-activity relationship studies with the oxazolidinones. Inhibition constants were calculated after a Logit fit of the data into the formula: % of control = 100/(1 + e[-B(X - A)]), where B is the slope of the model, X is the natural log of the inhibitor concentration and A is the natural log of the inhibitor concentration required to inhibit protein synthesis by 50% (ln IC50). When substituents at the 5-methyl position of the heterocyclic ring (B-substituent) were NHCOCH3, OH or Cl, the correlation coefficient was 0.87 between the MIC and IC50 values (for all compounds with MICs less than or equal to 16 micrograms/ml). The D-isomers of DuP 721 (A-substituent = CH3CO) and DuP 105 (A-substituent = CH3SO) gave MICs of 128 micrograms/ml and IC50s of greater than or equal to 50 micrograms/ml for protein synthesis, showing that only the L-isomers were active. By MIC testing, oxazolidinones with the B-substituent of NHCOCH3 and the A-substituent of CH3CO, NO2, CH3S, CH3SO2 or (CH3)2CH had comparable antibacterial potency; however, pulse labelling analysis showed that compounds with an A-substituent of CH3CO or NO2 were more potent inhibitors of protein synthesis.

  3. QUANTITAVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR OF ANTIMALARIAL 1,10-PHENANTHROLINE DERIVATIVES COMPOUNDS

    Directory of Open Access Journals (Sweden)

    Ruslin Hadanu

    2010-06-01

    Full Text Available Quantitative Electronic Structure-Activity Relationship (QSAR analysis of a series of 1,10-phenanthroline derivatives as antiplasmodial compounds have been conducted using atomic net charges (q, dipole moment (μ ELUMO, EHOMO, polarizability (α and log P as the descriptors. The descriptors were obtained from computational chemistry method using semi-empirical PM3. Antiplasmodial activities were taken as the activity of the drugs  against  chloroquine-resistant Plasmodium falciparum FCR3 strain and are presented as the value of ln (1/IC50 where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best model of QSAR model was determine by multiple linear regression method and giving equation of QSAR: ln 1/IC50  =  3.732 + (5.098 qC5 + (7.051 qC7 + (36.696 qC9 + (41.467 qC11 -(135.497 qC12 + (0.332 μ -                    (0.170 α + (0.757 log P. The equation was significant on the 95% level with statistical parameters: n=16; r=0.987; r2= 0.975; SE=0.317;  Fcalc/Ftable = 15.337 and gave the PRESS=0.707. Its means that there were only a relatively few deviations between the experimental and theoretical data of antimalarial activity.   Keywords: QSAR, antimalarial, semi-empirical method, 1,10-phenanthroline.

  4. Validation of Quantitative Structure-Activity Relationship (QSAR Model for Photosensitizer Activity Prediction

    Directory of Open Access Journals (Sweden)

    Sharifuddin M. Zain

    2011-11-01

    Full Text Available Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA method. Based on the method, r2 value, r2 (CV value and r2 prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC50 values ranging from 0.39 µM to 7.04 µM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r2 prediction for external test set of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.

  5. A Review of Recent Advances towards the Development of (Quantitative) Structure-Activity Relationships for Metallic Nanomaterials.

    NARCIS (Netherlands)

    Chen, Guangchao; Vijver, Martina G; Xiao, Yinlong; Peijnenburg, Willie J G M

    2017-01-01

    Gathering required information in a fast and inexpensive way is essential for assessing the risks of engineered nanomaterials (ENMs). The extension of conventional (quantitative) structure-activity relationships ((Q)SARs) approach to nanotoxicology, i.e., nano-(Q)SARs, is a possible solution. The

  6. Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein

    DEFF Research Database (Denmark)

    Zhang, Hang; Xiong, Xiao-feng; Boesgaard, Michael W

    2017-01-01

    that specifically inhibit signaling mediated by the Gq subfamily. In this study we exploit a newly developed synthetic strategy for this compound class in the design, synthesis, and pharmacological evaluation of eight new analogues of YM-254890. These structure-activity relationship studies led to the discovery...

  7. Quantitative structure-activity relationship modeling of the toxicity of organothiophosphate pesticides to Daphnia magna and Cyprinus carpio

    NARCIS (Netherlands)

    Zvinavashe, E.; Du, T.; Griff, T.; Berg, van den J.H.J.; Soffers, A.E.M.F.; Vervoort, J.J.M.; Murk, A.J.; Rietjens, I.

    2009-01-01

    Within the REACH regulatory framework in the EU, quantitative structure-activity relationships (QSAR) models are expected to help reduce the number of animals used for experimental testing. The objective of this study was to develop QSAR models to describe the acute toxicity of organothiophosphate

  8. Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships (MCBIOS)

    Science.gov (United States)

    Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships Jie Liu1,2, Richard Judson1, Matthew T. Martin1, Huixiao Hong3, Imran Shah1 1National Center for Computational Toxicology (NCCT), US EPA, RTP, NC...

  9. Discovery and Structure-Activity Relationship of a Bioactive Fragment of ELABELA that Modulates Vascular and Cardiac Functions

    NARCIS (Netherlands)

    Murza, Alexandre; Sainsily, Xavier; Coquerel, David; Côté, Jérôme; Marx, Patricia; Besserer-Offroy, Élie; Longpré, Jean-Michel; Lainé, Jean; Reversade, Bruno; Salvail, Dany; Leduc, Richard; Dumaine, Robert; Lesur, Olivier; Auger-Messier, Mannix; Sarret, Philippe; Marsault, Éric

    2016-01-01

    ELABELA (ELA) was recently discovered as a novel endogenous ligand of the apelin receptor (APJ), a G protein-coupled receptor. ELA signaling was demonstrated to be crucial for normal heart and vasculature development during embryogenesis. We delineate here ELA's structure- activity relationships and

  10. 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.

  11. Structure-activity relationship analysis of cytotoxic cyanoguanidines: selection of CHS 828 as candidate drug

    Directory of Open Access Journals (Sweden)

    Gullbo Joachim

    2009-06-01

    ten cell lines were compared. Substances with similar structures correlated well, whilst substances with large differences in molecular structure demonstrated lower correlation coefficients. Conclusion According to this structure-activity relationship (SAR study, CHS 828 meets the requirements for optimal cytotoxic activity for this class of compounds.

  12. Quantitative structure-activity relationship analysis of substituted arylazo pyridone dyes in photocatalytic system: Experimental and theoretical study

    Energy Technology Data Exchange (ETDEWEB)

    Dostanić, J., E-mail: jasmina@nanosys.ihtm.bg.ac.rs [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Lončarević, D. [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia); Zlatar, M. [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, Njegoševa 12, 11000 Belgrade (Serbia); Vlahović, F. [University of Belgrade, Innovation center of the Faculty of Chemistry, 11000 Belgrade (Serbia); Jovanović, D.M. [University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Department of Catalysis and Chemical Engineering, Njegoševa 12, 11000 Belgrade (Serbia)

    2016-10-05

    Highlights: • Electronic effects of para substituted arylazo pyridone dyes. • Linear relationship between Hammett σ{sub p} constants and dyes photoreactivity. • The photocatalytic reactions facilitated by el.-acceptors and retarded by el.-donors. • Fukui functions to analyze the reactivity on concurrent sites within a molecule. • Hydroxyl radicals sustain attack from two reaction sites, depending on a substituent type. - Abstract: A series of arylazo pyridone dyes was synthesized by changing the type of the substituent group in the diazo moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The structural and electronic properties of the investigated dyes was calculated at the M062X/6-31 + G(d,p) level of theory. The observed good linear correlations between atomic charges and Hammett σ{sub p} constants provided a basis to discuss the transmission of electronic substituent effects through a dye framework. The reactivity of synthesized dyes was tested through their decolorization efficiency in TiO{sub 2} photocatalytic system (Degussa P-25). Quantitative structure-activity relationship analysis revealed a strong correlation between reactivity of investigated dyes and Hammett substituent constants. The reaction was facilitated by electron-withdrawing groups, and retarded by electron-donating ones. Quantum mechanical calculations was used in order to describe the mechanism of the photocatalytic oxidation reactions of investigated dyes and interpret their reactivities within the framework of the Density Functional Theory (DFT). According to DFT based reactivity descriptors, i.e. Fukui functions and local softness, the active site moves from azo nitrogen atom linked to benzene ring to pyridone carbon atom linked to azo bond, going from dyes with electron-donating groups to dyes with electron-withdrawing groups.

  13. Quantitative structure-activity relationship analysis of substituted arylazo pyridone dyes in photocatalytic system: Experimental and theoretical study

    International Nuclear Information System (INIS)

    Dostanić, J.; Lončarević, D.; Zlatar, M.; Vlahović, F.; Jovanović, D.M.

    2016-01-01

    Highlights: • Electronic effects of para substituted arylazo pyridone dyes. • Linear relationship between Hammett σ_p constants and dyes photoreactivity. • The photocatalytic reactions facilitated by el.-acceptors and retarded by el.-donors. • Fukui functions to analyze the reactivity on concurrent sites within a molecule. • Hydroxyl radicals sustain attack from two reaction sites, depending on a substituent type. - Abstract: A series of arylazo pyridone dyes was synthesized by changing the type of the substituent group in the diazo moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The structural and electronic properties of the investigated dyes was calculated at the M062X/6-31 + G(d,p) level of theory. The observed good linear correlations between atomic charges and Hammett σ_p constants provided a basis to discuss the transmission of electronic substituent effects through a dye framework. The reactivity of synthesized dyes was tested through their decolorization efficiency in TiO_2 photocatalytic system (Degussa P-25). Quantitative structure-activity relationship analysis revealed a strong correlation between reactivity of investigated dyes and Hammett substituent constants. The reaction was facilitated by electron-withdrawing groups, and retarded by electron-donating ones. Quantum mechanical calculations was used in order to describe the mechanism of the photocatalytic oxidation reactions of investigated dyes and interpret their reactivities within the framework of the Density Functional Theory (DFT). According to DFT based reactivity descriptors, i.e. Fukui functions and local softness, the active site moves from azo nitrogen atom linked to benzene ring to pyridone carbon atom linked to azo bond, going from dyes with electron-donating groups to dyes with electron-withdrawing groups.

  14. Investigating Interdimensional Relationships

    Science.gov (United States)

    Valentine, Keri Duncan

    2017-01-01

    The phrase "interdimensional relationships" may conjure images of UFOs, alien beings, wormholes, and even mystical powers. These notions of interdimensionality were not out of bounds in the middle school learners' experiences described in this article. However, these notions do not entirely capture the mathematical relationships…

  15. Isolation of Insecticidal Constituent from Ruta graveolens and Structure-Activity Relationship Studies against Stored-Food Pests (Coleoptera).

    Science.gov (United States)

    Jeon, Ju-Hyun; Lee, Sang-Guei; Lee, Hoi-Seon

    2015-08-01

    Isolates from essential oil extracted from the flowers and leaves of Ruta graveolens and commercial phenolic analogs were evaluated using fumigant and contact toxicity bioassays against adults of the stored-food pests Sitophilus zeamais, Sitophilus oryzae, and Lasioderma serricorne. The insecticidal activity of these compounds was then compared with that of the synthetic insecticide dichlorvos. To investigate the structure-activity relationships, the activity of 2-isopropyl-5-methylphenol and its analogs was examined against these stored-food pests. Based on the 50% lethal dose, the most toxic compound against S. zeamais was 3-isopropylephenol, followed by 2-isopropylphenol, 4-isopropylphenol, 5-isopropyl-2-methylphenol, 2-isopropyl-5-methylphenol, 3-methylphenol, and 2-methylphenol. Similar results were observed with phenolic compounds against S. oryzae. However, when 2-isopropyl-5-methylphenol isolated from R. graveolens oil and its structurally related analogs were used against L. serricorne, little or no insecticidal activity was found regardless of bioassay. These results indicate that introducing and changing the positions of functional groups in the phenol skeleton have an important effect on insecticidal activity of these compounds against stored-food pests.

  16. Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.

    Science.gov (United States)

    Bahl, Deepa; Athar, Fareeda; Soares, Milena Botelho Pereira; de Sá, Matheus Santos; Moreira, Diogo Rodrigo Magalhães; Srivastava, Rajendra Mohan; Leite, Ana Cristina Lima; Azam, Amir

    2010-09-15

    A useful concept for the rational design of antiparasitic drug candidates is the complexation of bioactive ligands with transition metals. In view of this, an investigation was conducted into a new set of metal complexes as potential antiplasmodium and antiamoebic agents, in order to examine the importance of metallic atoms, as well as the kind of sphere of co-ordination, in these biological properties. Four functionalized furyl-thiosemicarbazones (NT1-4) treated with divalent metals (Cu, Co, Pt, and Pd) to form the mononuclear metallic complexes of formula [M(L)2Cl2] or [M(L)Cl2] were examined. The pharmacological characterization, including assays against Plasmodium falciparum and Entamoeba histolytica, cytotoxicity to mammalian cells, and interaction with pBR 322 plasmid DNA was performed. Structure-activity relationship data revealed that the metallic complexation plays an essential role in antiprotozoal activity, rather than the simple presence of the ligand or metal alone. Important steps towards identification of novel antiplasmodium (NT1Cu, IC50 of 4.6 microM) and antiamoebic (NT2Pd, IC50 of 0.6 microM) drug prototypes were achieved. Of particular relevance to this work, these prototypes were able to reduce the proliferation of these parasites at concentrations that are not cytotoxic to mammalian cells. Copyright (c) 2010. Published by Elsevier Ltd.

  17. A quantitative structure-activity relationship to predict efficacy of granular activated carbon adsorption to control emerging contaminants.

    Science.gov (United States)

    Kennicutt, A R; Morkowchuk, L; Krein, M; Breneman, C M; Kilduff, J E

    2016-08-01

    A quantitative structure-activity relationship was developed to predict the efficacy of carbon adsorption as a control technology for endocrine-disrupting compounds, pharmaceuticals, and components of personal care products, as a tool for water quality professionals to protect public health. Here, we expand previous work to investigate a broad spectrum of molecular descriptors including subdivided surface areas, adjacency and distance matrix descriptors, electrostatic partial charges, potential energy descriptors, conformation-dependent charge descriptors, and Transferable Atom Equivalent (TAE) descriptors that characterize the regional electronic properties of molecules. We compare the efficacy of linear (Partial Least Squares) and non-linear (Support Vector Machine) machine learning methods to describe a broad chemical space and produce a user-friendly model. We employ cross-validation, y-scrambling, and external validation for quality control. The recommended Support Vector Machine model trained on 95 compounds having 23 descriptors offered a good balance between good performance statistics, low error, and low probability of over-fitting while describing a wide range of chemical features. The cross-validated model using a log-uptake (qe) response calculated at an aqueous equilibrium concentration (Ce) of 1 μM described the training dataset with an r(2) of 0.932, had a cross-validated r(2) of 0.833, and an average residual of 0.14 log units.

  18. Antiparasitic activity of natural and semi-synthetic tirucallane triterpenoids from Schinus terebinthifolius (Anacardiaceae): structure/activity relationships.

    Science.gov (United States)

    Morais, Thiago R; da Costa-Silva, Thais A; Tempone, Andre G; Borborema, Samanta Etel T; Scotti, Marcus T; de Sousa, Raquel Maria F; Araujo, Ana Carolina C; de Oliveira, Alberto; de Morais, Sérgio Antônio L; Sartorelli, Patricia; Lago, João Henrique G

    2014-05-05

    Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae), and nine semi-synthetic derivatives were investigated against Leishmania (L.) infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR) data as well as electrospray ionization mass spectrometry (ESI-MS). Additionally, structure-activity relationships were performed using Decision Trees.

  19. Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae: Structure/Activity Relationships

    Directory of Open Access Journals (Sweden)

    Thiago R. Morais

    2014-05-01

    Full Text Available Leishmaniasis and Chagas are diseases caused by parasitic protozoans that affect the poorest population in the World, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, the discovery of novel, safe and more efficacious drugs is essential. In this work, the in vitro antiparasitic activity and mammalian cytotoxicity of three natural tirucallane triterpenoids, isolated from leaves of Schinus terebinthifolius (Anacardiaceae, and nine semi-synthetic derivatives were investigated against Leishmania (L. infantum and Trypanosoma cruzi. Trypomastigotes of T. cruzi were the most susceptible parasites and seven compounds demonstrated a trypanocidal activity with IC50 values in the range between 15 and 58 µg/mL. Four compounds demonstrated selectivity towards the intracellular amastigotes of Leishmania, with IC50 values in the range between 28 and 97 µg/mL. The complete characterization of triterpenoids was afforded after thorough analysis of nuclear magnetic resonance (NMR data as well as electrospray ionization mass spectrometry (ESI-MS. Additionally, structure-activity relationships were performed using Decision Trees.

  20. Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

    Science.gov (United States)

    Kim, In-Hae; Park, Yong-Kyu; Nishiwaki, Hisashi; Hammock, Bruce D; Nishi, Kosuke

    2015-11-15

    Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as a secondary pharmacophore. A tert-butyl group (16) on the alpha carbon was found to yield most potent inhibition on the target enzyme. A 4-50-fold drop in inhibition was induced by other substituents such as aryls, substituted aryls, cycloalkyls, and alkyls. Then, the modification of the O-substituents on the phosphonate function revealed that diethyl groups (16 and 23) were preferable for inhibition to other longer alkyls or substituted alkyls. In amide compounds with the optimized diethylphosphonate moiety and an alkyl substitution such as adamantane (16), tetrahydronaphthalene (31), or adamantanemethane (36), highly potent inhibitions were gained. In addition, the resulting potent amide-phosphonate compounds had reasonable water solubility, suggesting that substituted phosphonates in amide inhibitors are effective for both inhibition potency on the human sEH and water solubility as a secondary pharmacophore. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Quantitative structure-activity relationships of the antimalarial agent artemisinin and some of its derivatives - a DFT approach.

    Science.gov (United States)

    Rajkhowa, Sanchaita; Hussain, Iftikar; Hazarika, Kalyan K; Sarmah, Pubalee; Deka, Ramesh Chandra

    2013-09-01

    Artemisinin form the most important class of antimalarial agents currently available, and is a unique sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many derivatives of artemisinin were prepared. A comparative study on the chemical reactivity of artemisinin and some of its derivatives is performed using density functional theory (DFT) calculations. DFT based global and local reactivity descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity calculated at the optimized geometries are used to investigate the usefulness of these descriptors for understanding the reactive nature and reactive sites of the molecules. Multiple regression analysis is applied to build up a quantitative structure-activity relationship (QSAR) model based on the DFT based descriptors against the chloroquine-resistant, mefloquine-sensitive Plasmodium falciparum W-2 clone.

  2. Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.

    Science.gov (United States)

    Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L

    2016-03-23

    Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. 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.

  4. A structure-activity relationship study on antiosteoclastogenesis effect of triterpenoids from the leaves of loquat (Eriobotrya japonica).

    Science.gov (United States)

    Tan, Hui; Ashour, Ahmed; Katakura, Yoshinori; Shimizu, Kuniyoshi

    2015-04-15

    Our previous results elucidated that the leaves of Eriobotrya japonica possessed the potential to suppress ovariectomy-induced bone mineral density deterioration, and ursolic acid, the major bioactive component in these leaves, suppressed the osteoclast differentiation. The aim of this study was to discover more candidates for development of novel antiosteoclastogenesis agents from the leaves of E. japonica. Phytochemical analysis following a cell-based osteoclastic tartrate-resistant acid phosphatase (TRAP) activity assay revealed 11 more compounds with a potent antiosteoclastogenesis effect. The potency of ursane-type triterpenoids from the leaves of E. japonica prompted us to investigate the structure-activity relationships underlying their antiosteoclastogenesis. The results revealed that both the hydroxyl group at C-3 and the carboxylic group at C-17 played indispensable roles in the antiosteoclastogenesis activity of ursane-type triterpenoids. The configuration at C-3 (a beta-form of the hydroxyl group) was found to be important for this activity. While introducing a hydroxyl group at C-19 increased the inhibitory activity of ursane-type triterpenoids carrying an alpha-form hydroxyl group at C-3. The bioactivity analyses of ursolic acid and oleanolic acid demonstrated that the antiosteoclastogenesis effect of ursolic acid may be related to different positions of the C-29 and C-30 methyl groups on the E-ring, since oleanolic acid showed limited activity. The addition of a hydroxyl group at C-2 would dramatically improve the inhibition of oleanane-type triterpenoids. Collectively, these findings could provide important clues for the improvement of multi-targeted antiosteoclastogenesis agents from the leaves of E. japonica. Copyright © 2015 Elsevier GmbH. All rights reserved.

  5. Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567.

    Science.gov (United States)

    Kuduk, Scott D; Di Marco, Christina N; Bodmer-Narkevitch, Vera; Cook, Sean P; Cato, Matthew J; Jovanovska, Aneta; Urban, Mark O; Leitl, Michael; Sain, Nova; Liang, Annie; Spencer, Robert H; Kane, Stefanie A; Hartman, George D; Bilodeau, Mark T

    2010-01-20

    The synthesis, structure-activity relationship (SAR), and pharmacological evaluation of analogs of the acid-sensing ion channel (ASIC) inhibitor A-317567 are reported. It was found that the compound with an acetylenic linkage was the most potent ASIC-3 channel blocker. This compound reversed mechanical hypersensitivity in the rat iodoacetate model of osteoarthritis pain, although sedation was noted. Sedation was also observed in ASIC-3 knockout mice, questioning whether sedation and antinociception are mediated via a non-ASIC-3 specific mechanism.

  6. Obscure phenomena in statistical analysis of quantitative structure-activity relationships. Part 1: Multicollinearity of physicochemical descriptors.

    Science.gov (United States)

    Mager, P P; Rothe, H

    1990-10-01

    Multicollinearity of physicochemical descriptors leads to serious consequences in quantitative structure-activity relationship (QSAR) analysis, such as incorrect estimators and test statistics of regression coefficients of the ordinary least-squares (OLS) model applied usually to QSARs. Beside the diagnosis of the known simple collinearity, principal component regression analysis (PCRA) also allows the diagnosis of various types of multicollinearity. Only if the absolute values of PCRA estimators are order statistics that decrease monotonically, the effects of multicollinearity can be circumvented. Otherwise, obscure phenomena may be observed, such as good data recognition but low predictive model power of a QSAR model.

  7. Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.

    Science.gov (United States)

    Sun, Wenlong; Zhuang, Chunlin; Li, Xia; Zhang, Bowei; Lu, Xinhua; Zheng, Zhihui; Dong, Yuesheng

    2017-08-01

    Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

    Science.gov (United States)

    Li, Minyong; Xia, Lin

    2007-11-01

    In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

  9. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

    DEFF Research Database (Denmark)

    Gimenéz-Arnau, Elena; Andersen, K E; Bruze, M

    2000-01-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application...

  10. Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship.

    Science.gov (United States)

    Hou, Jin-Jun; Shen, Yao; Yang, Zhou; Fang, Lin; Cai, Lu-Ying; Yao, Shuai; Long, Hua-Li; Wu, Wan-Ying; Guo, De-An

    2017-10-01

    Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC 50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  11. Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study

    NARCIS (Netherlands)

    Hendriks, Jerome J. A.; de Vries, Helga E.; van der Pol, Susanne M. A.; van den Berg, Timo K.; van Tol, Eric A. F.; Dijkstra, Christine D.

    2003-01-01

    Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds,

  12. p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

    Science.gov (United States)

    Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

    2016-07-25

    We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

  13. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

    Science.gov (United States)

    Arnau, E G; Andersen, K E; Bruze, M; Frosch, P J; Johansen, J D; Menné, T; Rastogi, S C; White, I R; Lepoittevin, J P

    2000-12-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

  14. Molecular Descriptors Family on Structure Activity Relationships 6. Octanol-Water Partition Coefficient of Polychlorinated Biphenyls

    Directory of Open Access Journals (Sweden)

    Lorentz JÄNTSCHI

    2006-01-01

    Full Text Available Octanol-water partition coefficient of two hundred and six polychlorinated biphenyls was model by the use of an original method based on complex information obtained from compounds structure. The regression analysis shows that best results are obtained in four-varied model (r2 = 0.9168. The prediction ability of the model was studied through leave-one-out analysis (r2cv(loo = 0.9093 and in training and test sets analysis. Modeling the octanol-water partition coefficient of polychlorinated biphenyls by integration of complex structural information provide a stable and performing four-varied model, allowing us to make remarks about relationship between structure of polychlorinated biphenyls and associated octanol-water partition coefficients.

  15. Synthesis and structure-activity relationship exploration of some potent anti-cancer phenyl amidrazone derivatives.

    Science.gov (United States)

    Habashneh, Almeqdad Y; El-Abadelah, Mustafa M; Bardaweel, Sanaa K; Taha, Mutasem O

    2017-12-04

    Amidrazones have been reported to have significant anti-tumor properties against several cancer cell lines. The current project aims to profile the structure-anticancer activity relationship of phenyl-amidrazons. Fifteen phenyl-amidrazone-piperazine derivatives were prepared and tested against four cancer cell lines (leukemia, prostate, breast and colon cancers). Six compounds illustrated low micromolar anticancer IC50 values, while the remaining compounds were either inactive or of moderate potencies. All compounds were virtually nontoxic against normal fibroblast cells. Docking into the oncogenic kinase bcr/abl illustrated the critical importance of (i) p-halogen substituent on the ligand's phenyl ring and (ii) the presence of positive ionizable moiety at the ligand's piperazine fragment for anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Nε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling.

    Science.gov (United States)

    Wodtke, Robert; Hauser, Christoph; Ruiz-Gómez, Gloria; Jäckel, Elisabeth; Bauer, David; Lohse, Martin; Wong, Alan; Pufe, Johanna; Ludwig, Friedrich-Alexander; Fischer, Steffen; Hauser, Sandra; Greif, Dieter; Pisabarro, M Teresa; Pietzsch, Jens; Pietsch, Markus; Löser, Reik

    2018-05-24

    Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N ε -acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M -1 s -1 , which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

  17. Structure-activity relationships of lanostane-type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors.

    Science.gov (United States)

    Fatmawati, Sri; Kondo, Ryuichiro; Shimizu, Kuniyoshi

    2013-11-01

    A series of lanostane-type triterpenoids, identified as ganoderma alcohols and ganoderma acids, were isolated from the fruiting body of Ganoderma lingzhi. Some of these compounds were confirmed as active inhibitors of the in vitro human recombinant aldose reductase. This paper aims to explain the structural requirement for α-glucosidase inhibition. Our structure-activity studies of ganoderma alcohols showed that the OH substituent at C-3 and the double-bond moiety at C-24 and C-25 are necessary to increase α-glucosidase inhibitory activity. The structure-activity relationships of ganoderma acids revealed that the OH substituent at C-11 is an important feature and that the carboxylic group in the side chain is essential for the recognition of α-glucosidase inhibitory activity. Moreover, the double-bond moiety at C-20 and C-22 in the side chain and the OH substituent at C-3 of ganoderma acids improve α-glucosidase inhibitory activity. These results provide an approach with which to consider the structural requirements of lanostane-type triterpenoids from G. lingzhi. An understanding of these requirements is considered necessary in order to improve a new type of α-glucosidase inhibitor. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. A Structure-Activity Relationship (SAR Study of Neolignan Compounds with Anti-schistosomiasis Activity

    Directory of Open Access Journals (Sweden)

    Alves Claúdio N.

    2002-01-01

    Full Text Available A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors to be correlated to their biological activities. Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA, discriminant analysis (DA and the Kth nearest neighbor (KNN method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE, molecular refractivity (MR and charge on the C19 carbon atom (Q19. These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.

  19. Structure-activity relationships and prediction of the phototoxicity and phototoxic potential of new drugs.

    Science.gov (United States)

    Barratt, Martin D

    2004-11-01

    Relationships between the structure and properties of chemicals can be programmed into knowledge-based systems such as DEREK for Windows (DEREK is an acronym for "Deductive Estimation of Risk from Existing Knowledge"). The DEREK for Windows computer system contains a subset of over 60 rules describing chemical substructures (toxophores) responsible for skin sensitisation. As part of the European Phototox Project, the rule base was supplemented by a number of rules for the prospective identification of photoallergens, either by extension of the scope of existing rules or by the generation of new rules where a sound mechanistic rationale for the biological activity could be established. The scope of the rules for photoallergenicity was then further refined by assessment against a list of chemicals identified as photosensitisers by the Centro de Farmacovigilancia de la Comunidad Valenciana, Valencia, Spain. This paper contains an analysis of the mechanistic bases of activity for eight important groups of photoallergens and phototoxins, together with rules for the prospective identification of the photobiological activity of new or untested chemicals belonging to those classes. The mechanism of action of one additional chemical, nitrofurantoin, is well established; however, it was deemed inappropriate to write a rule on the basis of a single chemical structure.

  20. Benzoxazolone carboxamides as potent acid ceramidase inhibitors: Synthesis and structure-activity relationship (SAR) studies

    DEFF Research Database (Denmark)

    Bach, Anders

    2015-01-01

    be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We...... examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic...

  1. Synthesis and structure-activity relationship studies of furan-ring fused chalcones as antiproliferative agents.

    Science.gov (United States)

    Saito, Yusuke; Kishimoto, Maho; Yoshizawa, Yuko; Kawaii, Satoru

    2015-02-01

    As part of our continuing investigation of flavonoid derivatives as potential anticancer substances, the synthesis of 25 cinnamoyl derivatives of benzofuran as furan-fused chalcones was carried-out and these compounds were further evaluated for their antiproliferative activity towards HL60 promyelocytic leukemia cells. In comparison with 2',4'-dihydroxychalcone, attachment of a furan moiety on the A-ring enhanced activity by more than twofold. Benzofurans may be useful in the design of biologically active flavonoids. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

    Science.gov (United States)

    Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

    2017-04-01

    Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

  3. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study.

    Science.gov (United States)

    Proença, Carina; Freitas, Marisa; Ribeiro, Daniela; Oliveira, Eduardo F T; Sousa, Joana L C; Tomé, Sara M; Ramos, Maria J; Silva, Artur M S; Fernandes, Pedro A; Fernandes, Eduarda

    2017-12-01

    α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme's activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure-activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC 50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.

  4. Multistep continuous-flow synthesis in medicinal chemistry: discovery and preliminary structure-activity relationships of CCR8 ligands.

    Science.gov (United States)

    Petersen, Trine P; Mirsharghi, Sahar; Rummel, Pia C; Thiele, Stefanie; Rosenkilde, Mette M; Ritzén, Andreas; Ulven, Trond

    2013-07-08

    A three-step continuous-flow synthesis system and its application to the assembly of a new series of chemokine receptor ligands directly from commercial building blocks is reported. No scavenger columns or solvent switches are necessary to recover the desired test compounds, which were obtained in overall yields of 49-94%. The system is modular and flexible, and the individual steps of the sequence can be interchanged with similar outcome, extending the scope of the chemistry. Biological evaluation confirmed activity on the chemokine CCR8 receptor and provided initial structure-activity-relationship (SAR) information for this new ligand series, with the most potent member displaying full agonist activity with single-digit nanomolar potency. To the best of our knowledge, this represents the first published example of efficient use of multistep flow synthesis combined with biological testing and SAR studies in medicinal chemistry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessments.

    Science.gov (United States)

    Comber, Mike H I; Walker, John D; Watts, Chris; Hermens, Joop

    2003-08-01

    The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed.

  6. Structure-activity relationship of 9-methylstreptimidone, a compound that induces apoptosis selectively in adult T-cell leukemia cells.

    Science.gov (United States)

    Takeiri, Masatoshi; Ota, Eisuke; Nishiyama, Shigeru; Kiyota, Hiromasa; Umezawa, Kazuo

    2012-01-01

    We previously reported that 9-methylstreptimidone, a piperidine compound isolated from a culture filtrate of Streptomyces, induces apoptosis selectively in adult T-cell leukemia cells. It was screened for a compound that inhibits LPS-induced NF-kappaB and NO production in mouse macrophages. However, 9-methystreptimidone is poorly obtained from the producing microorganism and difficult to synthesize. Therefore, in the present research, we studied the structure-activity relationship to look for new selective inhibitors. We found that the structure of the unsaturated hydrophobic portion of 9-methylstreptimidone was essential for the inhibition of LPS-induced NO production. Among the 9-methylstreptimidone-related compounds tested, (+/-)-4,alpha-diepi-streptovitacin A inhibited NO production in macrophage-like cells as potently as 9-methylstreptimidone and without cellular toxicity. Moreover, this compound selectively induced apoptosis in adult T-cell leukemia MT-1 cells.

  7. Non-linear quantitative structure-activity relationship for adenine derivatives as competitive inhibitors of adenosine deaminase

    International Nuclear Information System (INIS)

    Sadat Hayatshahi, Sayyed Hamed; Abdolmaleki, Parviz; Safarian, Shahrokh; Khajeh, Khosro

    2005-01-01

    Logistic regression and artificial neural networks have been developed as two non-linear models to establish quantitative structure-activity relationships between structural descriptors and biochemical activity of adenosine based competitive inhibitors, toward adenosine deaminase. The training set included 24 compounds with known k i values. The models were trained to solve two-class problems. Unlike the previous work in which multiple linear regression was used, the highest of positive charge on the molecules was recognized to be in close relation with their inhibition activity, while the electric charge on atom N1 of adenosine was found to be a poor descriptor. Consequently, the previously developed equation was improved and the newly formed one could predict the class of 91.66% of compounds correctly. Also optimized 2-3-1 and 3-4-1 neural networks could increase this rate to 95.83%

  8. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities.

    Science.gov (United States)

    Akhtar, Jawaid; Khan, Ahsan Ahmed; Ali, Zulphikar; Haider, Rafi; Shahar Yar, M

    2017-01-05

    The present review article offers a detailed account of the design strategies employed for the synthesis of nitrogen-containing anticancer agents. The results of different studies describe the N-heterocyclic ring system is a core structure in many synthetic compounds exhibiting a broad range of biological activities. Benzimidazole, benzothiazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, triazoles, quinolines and quinazolines including others drugs containing pyridazine, pyridine and pyrimidines are covered. The following studies of these compounds suggested that these compounds showed their antitumor activities through multiple mechanisms including inhibiting protein kinase (CDK, MK-2, PLK1, kinesin-like protein Eg5 and IKK), topoisomerase I and II, microtubule inhibition, and many others. Our concise representation exploits the design and anticancer potency of these compounds. The direct comparison of anticancer activities with the standard enables a systematic analysis of the structure-activity relationship among the series. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Synthesis and Structure-Activity Relationships of Novel Amino/Nitro Substituted 3-Arylcoumarins as Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Ysabel Santos

    2013-01-01

    Full Text Available A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive and Escherichia coli (Gram-negative was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin. The preliminary structure-activity relationship (SAR study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported.

  10. Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.

    Science.gov (United States)

    Menezes, Carla M S; Rivera, Gildardo; Alves, Marina A; do Amaral, Daniel N; Thibaut, Jean Pierre B; Noël, François; Barreiro, Eliezer J; Lima, Lídia M

    2012-06-01

    The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. © 2012 John Wiley & Sons A/S.

  11. Structure-activity relationship of pentacylic triterpene esters from Uncaria rhynchophylla as inhibitors of phospholipase Cgamma1.

    Science.gov (United States)

    Lee, Ji Suk; Yoo, Hunseung; Suh, Young Ger; Jung, Jae Kyung; Kim, Jinwoong

    2008-10-01

    A systematic structure-activity relationship of 3beta-hydroxy-27- P- E-coumaroyloxyurs-12-en-28-oic acid ( 7), a triterpene ester isolated from UNCARIA RHYNCHOPHYLLA as a phospholipase Cgamma1 inhibitor, was undertaken with a view toward elucidating its chemical mode of action on PLCgamma1. Related derivatives and analogues of 7 were synthesized and their inhibitory activities against PLCgamma1 were evaluated IN VITRO. The results indicate that 3-OH and 27-esterification may be essential, and that 28-COOH and the 2' double bond appear to be important for activity. Furthermore, the compound possessing a P-coumaroyloxy at position 27 rather than at the 3 and 28 positions shows the greatest inhibitory activity against PLCgamma1. Therefore, this inhibitor will be providing a chemical lead for the further development of cancer chemopreventive or cancer chemotherapeutic agents that have lower toxicity against normal tissues.

  12. Structure-Activity Relationship Studies of the Cyclic Depsipeptide Natural Product YM-254890, Targeting the Gq Protein.

    Science.gov (United States)

    Zhang, Hang; Xiong, Xiao-Feng; Boesgaard, Michael W; Underwood, Christina R; Bräuner-Osborne, Hans; Strømgaard, Kristian

    2017-06-07

    Extracellular signals perceived by G protein-coupled receptors are transmitted via G proteins, and subsequent intracellular signaling cascades result in a plethora of physiological responses. The natural product cyclic depsipeptides YM-254890 and FR900359 are the only known compounds that specifically inhibit signaling mediated by the G q subfamily. In this study we exploit a newly developed synthetic strategy for this compound class in the design, synthesis, and pharmacological evaluation of eight new analogues of YM-254890. These structure-activity relationship studies led to the discovery of three new analogues, YM-13, YM-14, and YM-18, which displayed potent and selective G q inhibitory activity. This provides pertinent information for the understanding of the G q inhibitory mechanism by this class of compounds and importantly provides a pathway for the development of labeled YM-254890 analogues. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors.

    Science.gov (United States)

    Zeng, Debin; Ma, Yuying; Zhang, Rui; Nie, Quandeng; Cui, Zhengjie; Wang, Yaxin; Shang, Luqing; Yin, Zheng

    2016-04-01

    α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26μM, 1.88±0.35μM and 1.52±0.31μM, respectively) and favorable CC50 values (CC50>100μM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Negative inotropism of terpenes on guinea pig left atrium: structure-activity relationships.

    Science.gov (United States)

    Vasconcelos, Carla M L; Oliveira, Ingrid S N; Santos, José N A; Souza, Américo A; Menezes-Filho, José E R; Silva Neto, Júlio A; Lima, Tamires C; de Sousa, Damião P

    2018-06-01

    The aim of this work was to evaluate the pharmacological effect of seven structurally related terpenes on the contractility of cardiac muscle. The effect of terpenes was studied on isolated electrically driven guinea pig left atrium. From concentration-response curves for inotropic effect were determined the EC 50 and relative potency of such terpenes. Our results revealed that all terpenes, except phytol, showed ability to reduce the contractile response of guinea pig left atrium. Further, relative potency was directly related to the number of isoprene units and to the lipophilicity of the compounds. For example, sesquiterpenes farnesol and nerolidol showed higher relative potency when compared with the monoterpenes citronellol, geraniol and nerol. We can conclude that most of the evaluated terpenes showed a promising negative inotropism on the atrial muscle. Future studies are necessary to investigate their action mechanism.

  15. Structure-activity relationships of benzimidazole-based glutaminyl cyclase inhibitors featuring a heteroaryl scaffold.

    Science.gov (United States)

    Ramsbeck, Daniel; Buchholz, Mirko; Koch, Birgit; Böhme, Livia; Hoffmann, Torsten; Demuth, Hans-Ulrich; Heiser, Ulrich

    2013-09-12

    Glutaminyl cyclase (hQC) has emerged as a new potential target for the treatment of Alzheimer's disease (AD). The inhibition of hQC prevents of the formation of the Aβ3(pE)-40,42 species which were shown to be of elevated neurotoxicity and are likely to act as a seeding core, leading to an accelerated formation of Aβ-oligomers and fibrils. This work presents a new class of inhibitors of hQC, resulting from a pharmacophore-based screen. Hit molecules were identified, containing benzimidazole as the metal binding group connected to 1,3,4-oxadiazole as the central scaffold. The subsequent optimization resulted in benzimidazolyl-1,3,4-thiadiazoles and -1,2,3-triazoles with an inhibitory potency in the nanomolar range. Further investigation into the potential binding mode of the new compound classes combined molecular docking and site directed mutagenesis studies.

  16. In vitro toxicological effects of estrogenic mycotoxins on human placental cells: Structure activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Prouillac, Caroline, E-mail: c.prouillac@vetagro-sup.fr [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Koraichi, Farah; Videmann, Bernadette; Mazallon, Michelle [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France); Rodriguez, Frédéric; Baltas, Michel [Université Paul Sabatier, SPCMIB-UMR5068, Laboratoire de Synthèse et de Physicochimie des Molécules d' Intérêt Biologique, 118 route de Narbonne, 31062 TOULOUSE cedex 9 (France); Lecoeur, Sylvaine [Université Lyon, US/C 1233 INRA VetAgroSup, Métabolisme et Toxicologie Comparée des Xénobiotiques, 1 avenue Bourgelat, BP 83, 69280 Marcy l' Etoile (France)

    2012-03-15

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  17. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

    2010-07-15

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  18. In vitro toxicological effects of estrogenic mycotoxins on human placental cells: Structure activity relationships

    International Nuclear Information System (INIS)

    Prouillac, Caroline; Koraichi, Farah; Videmann, Bernadette; Mazallon, Michelle; Rodriguez, Frédéric; Baltas, Michel; Lecoeur, Sylvaine

    2012-01-01

    Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to α- and β-zearalenol (αZEL and βZEL). These reduced metabolites possess estrogenic properties, αZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of αZEL and βΖΕL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARγ). Our results demonstrated that in spite of structure similarities between ZEN, αZEL and βZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. -- Highlights: ► ZEN and metabolites have differential effect on trophoblast differentiation. ► ZEN and metabolites have differential effect on ABC transporter expression. ► ZEN and metabolites effects involved nuclear receptors interaction.

  19. Quantitative structure-activation barrier relationship modeling for Diels-Alder ligations utilizing quantum chemical structural descriptors.

    Science.gov (United States)

    Nandi, Sisir; Monesi, Alessandro; Drgan, Viktor; Merzel, Franci; Novič, Marjana

    2013-10-30

    In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software. Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers. A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation.

  20. Structure-activity relationships of novel salicylaldehyde isonicotinoyl hydrazone (SIH analogs: iron chelation, anti-oxidant and cytotoxic properties.

    Directory of Open Access Journals (Sweden)

    Eliška Potůčková

    Full Text Available Salicylaldehyde isonicotinoyl hydrazone (SIH is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability. Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O, which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

  1. Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies

    Directory of Open Access Journals (Sweden)

    André Luiz Lourenço

    2015-04-01

    Full Text Available The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations.

  2. Novel Insights into Structure-Activity Relationships of N-Terminally Modified PACE4 Inhibitors.

    Science.gov (United States)

    Kwiatkowska, Anna; Couture, Frédéric; Levesque, Christine; Ly, Kévin; Beauchemin, Sophie; Desjardins, Roxane; Neugebauer, Witold; Dory, Yves L; Day, Robert

    2016-02-04

    PACE4 plays important roles in prostate cancer cell proliferation. The inhibition of this enzyme has been shown to slow prostate cancer progression and is emerging as a promising therapeutic strategy. In previous work, we developed a highly potent and selective PACE4 inhibitor, the multi-Leu (ML) peptide, an octapeptide with the sequence Ac-LLLLRVKR-NH2 . Here, with the objective of developing a useful compound for in vivo administration, we investigate the effect of N-terminal modifications. The inhibitory activity, toxicity, stability, and cell penetration properties of the resulting analogues were studied and compared to the unmodified inhibitor. Our results show that the incorporation of a polyethylene glycol (PEG) moiety leads to a loss of antiproliferative activity, whereas the attachment of a lipid chain preserves or improves it. However, the lipidated peptides are significantly more toxic when compared with their unmodified counterparts. Therefore, the best results were achieved not by the N-terminal extension but by the protection of both ends with the d-Leu residue and 4-amidinobenzylamide, which yielded the most stable inhibitor, with an excellent activity and toxicity profile. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

    International Nuclear Information System (INIS)

    Venkatapathy, Raghuraman; Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

    2009-01-01

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD 50 ]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD 50 ) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD 50 and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD 50 s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD 50 for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction

  4. Structure-activity relationship studies of 5,7-dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells.

    Science.gov (United States)

    Ninomiya, Masayuki; Nishida, Kyohei; Tanaka, Kaori; Watanabe, Kunitomo; Koketsu, Mamoru

    2013-07-01

    Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure-activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring.

  5. In Vitro Antioxidant versus Metal Ion Chelating Properties of Flavonoids: A Structure-Activity Investigation

    Science.gov (United States)

    Cherrak, Sabri Ahmed; Mokhtari-Soulimane, Nassima; Berroukeche, Farid; Bensenane, Bachir; Cherbonnel, Angéline; Merzouk, Hafida; Elhabiri, Mourad

    2016-01-01

    Natural flavonoids such as quercetin, (+)catechin and rutin as well as four methoxylated derivatives of quercetin used as models were investigated to elucidate their impact on the oxidant and antioxidant status of human red blood cells (RBCs). The impact of these compounds against metal toxicity was studied as well as their antiradical activities with DPPH assay. Antihemolytic experiments were conducted on quercetin, (+)catechin and rutin with excess of Fe, Cu and Zn (400 μM), and the oxidant (malondialdehyde, carbonyl proteins) and antioxidant (reduced glutathione, catalase activity) markers were evaluated. The results showed that Fe and Zn have the highest prooxidant effect (37 and 33% of hemolysis, respectively). Quercetin, rutin and (+)catechin exhibited strong antioxidant properties toward Fe, but this effect was decreased with respect to Zn ions. However, the Cu showed a weak antioxidant effect at the highest flavonoid concentration (200 μM), while a prooxidant effect was observed at the lowest flavonoid concentration (100 μM). These results are in agreement with the physico-chemical and antiradical data which demonstrated that binding of the metal ions (for FeNTA: (+)Catechin, KLFeNTA = 1.6(1) × 106 M-1 > Rutin, KLFeNTA = 2.0(9) × 105 M-1 > Quercetin, KLFeNTA = 1.0(7) × 105 M-1 > Q35OH, KLFeNTA = 6.3(8.7) × 104 M-1 > Quercetin3’4’OH and Quercetin 3OH, KLFeNTA ~ 2 × 104 M-1) reflects the (anti)oxidant status of the RBCs. This study reveals that flavonoids have both prooxidant and antioxidant activity depending on the nature and concentration of the flavonoids and metal ions. PMID:27788249

  6. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships

    DEFF Research Database (Denmark)

    Arnau, E G; Andersen, Klaus Ejner; Bruze, M

    2000-01-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships...... (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application......" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance...

  7. Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells.

    Science.gov (United States)

    Jiang, Wen-Jun; Daikonya, Akihiro; Ohkawara, Mitsuyoshi; Nemoto, Takashi; Noritake, Ryusuke; Takamiya, Tomoko; Kitanaka, Susumu; Iijima, Hiroshi

    2017-01-15

    We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R 3' =R 5' ). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q 2 value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Modeling the Dispersibility of Single Walled Carbon Nanotubes in Organic Solvents by Quantitative Structure-Activity Relationship Approach

    Science.gov (United States)

    Yilmaz, Hayriye; Rasulev, Bakhtiyor; Leszczynski, Jerzy

    2015-01-01

    The knowledge of physico-chemical properties of carbon nanotubes, including behavior in organic solvents is very important for design, manufacturing and utilizing of their counterparts with improved properties. In the present study a quantitative structure-activity/property relationship (QSAR/QSPR) approach was applied to predict the dispersibility of single walled carbon nanotubes (SWNTs) in various organic solvents. A number of additive descriptors and quantum-chemical descriptors were calculated and utilized to build QSAR models. The best predictability is shown by a 4-variable model. The model showed statistically good results (R2training = 0.797, Q2 = 0.665, R2test = 0.807), with high internal and external correlation coefficients. Presence of the X0Av descriptor and its negative term suggest that small size solvents have better SWCNTs solubility. Mass weighted descriptor ATS6m also indicates that heavier solvents (and small in size) most probably are better solvents for SWCNTs. The presence of the Dipole Z descriptor indicates that higher polarizability of the solvent molecule increases the solubility. The developed model and contributed descriptors can help to understand the mechanism of the dispersion process and predictorganic solvents that improve the dispersibility of SWNTs. PMID:28347035

  9. A Review of Recent Advances towards the Development of (Quantitative Structure-Activity Relationships for Metallic Nanomaterials

    Directory of Open Access Journals (Sweden)

    Guangchao Chen

    2017-08-01

    Full Text Available Gathering required information in a fast and inexpensive way is essential for assessing the risks of engineered nanomaterials (ENMs. The extension of conventional (quantitative structure-activity relationships ((QSARs approach to nanotoxicology, i.e., nano-(QSARs, is a possible solution. The preliminary attempts of correlating ENMs’ characteristics to the biological effects elicited by ENMs highlighted the potential applicability of (QSARs in the nanotoxicity field. This review discusses the current knowledge on the development of nano-(QSARs for metallic ENMs, on the aspects of data sources, reported nano-(QSARs, and mechanistic interpretation. An outlook is given on the further development of this frontier. As concluded, the used experimental data mainly concern the uptake of ENMs by different cell lines and the toxicity of ENMs to cells lines and Escherichia coli. The widely applied techniques of deriving models are linear and non-linear regressions, support vector machine, artificial neural network, k-nearest neighbors, etc. Concluded from the descriptors, surface properties of ENMs are seen as vital for the cellular uptake of ENMs; the capability of releasing ions and surface redox properties of ENMs are of importance for evaluating nanotoxicity. This review aims to present key advances in relevant nano-modeling studies and stimulate future research efforts in this quickly developing field of research.

  10. Modeling the Dispersibility of Single Walled Carbon Nanotubes in Organic Solvents by Quantitative Structure-Activity Relationship Approach

    Directory of Open Access Journals (Sweden)

    Hayriye Yilmaz

    2015-05-01

    Full Text Available The knowledge of physico-chemical properties of carbon nanotubes, including behavior in organic solvents is very important for design, manufacturing and utilizing of their counterparts with improved properties. In the present study a quantitative structure-activity/property relationship (QSAR/QSPR approach was applied to predict the dispersibility of single walled carbon nanotubes (SWNTs in various organic solvents. A number of additive descriptors and quantum-chemical descriptors were calculated and utilized to build QSAR models. The best predictability is shown by a 4-variable model. The model showed statistically good results (R2training = 0.797, Q2 = 0.665, R2test = 0.807, with high internal and external correlation coefficients. Presence of the X0Av descriptor and its negative term suggest that small size solvents have better SWCNTs solubility. Mass weighted descriptor ATS6m also indicates that heavier solvents (and small in size most probably are better solvents for SWCNTs. The presence of the Dipole Z descriptor indicates that higher polarizability of the solvent molecule increases the solubility. The developed model and contributed descriptors can help to understand the mechanism of the dispersion process and predictorganic solvents that improve the dispersibility of SWNTs.

  11. Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

    Science.gov (United States)

    Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

    2011-04-14

    Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

  12. Determination of boiling point of petrochemicals by gas chromatography-mass spectrometry and multivariate regression analysis of structural activity relationship.

    Science.gov (United States)

    Fakayode, Sayo O; Mitchell, Breanna S; Pollard, David A

    2014-08-01

    Accurate understanding of analyte boiling points (BP) is of critical importance in gas chromatographic (GC) separation and crude oil refinery operation in petrochemical industries. This study reported the first combined use of GC separation and partial-least-square (PLS1) multivariate regression analysis of petrochemical structural activity relationship (SAR) for accurate BP determination of two commercially available (D3710 and MA VHP) calibration gas mix samples. The results of the BP determination using PLS1 multivariate regression were further compared with the results of traditional simulated distillation method of BP determination. The developed PLS1 regression was able to correctly predict analytes BP in D3710 and MA VHP calibration gas mix samples, with a root-mean-square-%-relative-error (RMS%RE) of 6.4%, and 10.8% respectively. In contrast, the overall RMS%RE of 32.9% and 40.4%, respectively obtained for BP determination in D3710 and MA VHP using a traditional simulated distillation method were approximately four times larger than the corresponding RMS%RE of BP prediction using MRA, demonstrating the better predictive ability of MRA. The reported method is rapid, robust, and promising, and can be potentially used routinely for fast analysis, pattern recognition, and analyte BP determination in petrochemical industries. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors.

    Science.gov (United States)

    Ma, Fei; Liu, Jian; Zhou, Tingting; Lei, Min; Chen, Jing; Wang, Xiachang; Zhang, Yinan; Shen, Xu; Hu, Lihong

    2018-05-25

    Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC 50  = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF 3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC 50  = 16.8 μM) and 9d (IC 50  = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Structure-Activity Relationship of Curcumin: Role of the Methoxy Group in Anti-inflammatory and Anticolitis Effects of Curcumin.

    Science.gov (United States)

    Yang, Haixia; Du, Zheyuan; Wang, Weicang; Song, Mingyue; Sanidad, Katherine; Sukamtoh, Elvira; Zheng, Jennifer; Tian, Li; Xiao, Hang; Liu, Zhenhua; Zhang, Guodong

    2017-06-07

    Curcumin, a dietary compound from turmeric, has beneficial effects on inflammatory diseases such as inflammatory bowel disease. Most previous studies have focused on the structure-activity relationship of the thiol-reactive α,β-unsaturated carbonyl groups of curcumin, so little is known about the roles of methoxy groups in biological activities of curcumin. Here we synthesized a series of curcumin analogues with different substitution groups (R = H-, Br-, Cl-, F-, NO 2 -, CH 3 -, and OH-) to replace the methoxy group and evaluated their biological effects in vitro and in vivo. Curcumin, Cur-OH, and Cur-Br (25 μM) suppressed 74.91 ± 0.88, 77.75 ± 0.89, and 71.75 ± 0.90% of LPS-induced NO production, respectively (P 0.05). In the dextran sulfate sodium (DSS)-induced colitis mouse model, the Cur-Br analogue also showed a beneficial effect the same as curcumin (P 0.05). Together, the analogues have dramatically different effects on inflammation, supporting that the substitution group on the methoxy position plays an important role in the anti-inflammatory effects of curcumin. The methoxy group is a potential structural candidate for modification to design curcumin-based drugs for inflammatory diseases.

  15. Application of quantitative structure-activity relationship to the determination of binding constant based on fluorescence quenching

    Energy Technology Data Exchange (ETDEWEB)

    Wen Yingying [Department of Applied Chemistry, Yantai University, Yantai 264005 (China); Liu Huitao, E-mail: liuht-ytu@163.co [Department of Applied Chemistry, Yantai University, Yantai 264005 (China); Luan Feng; Gao Yuan [Department of Applied Chemistry, Yantai University, Yantai 264005 (China)

    2011-01-15

    Quantitative structure-activity relationship (QSAR) model was used to predict and explain binding constant (log K) determined by fluorescence quenching. This method allowed us to predict binding constants of a variety of compounds with human serum albumin (HSA) based on their structures alone. Stepwise multiple linear regression (MLR) and nonlinear radial basis function neural network (RBFNN) were performed to build the models. The statistical parameters provided by the MLR model (R{sup 2}=0.8521, RMS=0.2678) indicated satisfactory stability and predictive ability while the RBFNN predictive ability is somewhat superior (R{sup 2}=0.9245, RMS=0.1736). The proposed models were used to predict the binding constants of two bioactive components in traditional Chinese medicines (isoimperatorin and chrysophanol) whose experimental results were obtained in our laboratory and the predicted results were in good agreement with the experimental results. This QSAR approach can contribute to a better understanding of structural factors of the compounds responsible for drug-protein interactions, and can be useful in predicting the binding constants of other compounds. - Research Highlights: QSAR models for binding constants of some compounds to HSA were developed. The models provide a simple and straightforward way to predict binding constant. QSAR can give some insight into structural features related to binding behavior.

  16. Designing quantitative structure activity relationships to predict specific toxic endpoints for polybrominated diphenyl ethers in mammalian cells.

    Science.gov (United States)

    Rawat, S; Bruce, E D

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are known as effective flame retardants and have vast industrial application in products like plastics, building materials and textiles. They are found to be structurally similar to thyroid hormones that are responsible for regulating metabolism in the body. Structural similarity with the hormones poses a threat to human health because, once in the system, PBDEs have the potential to affect thyroid hormone transport and metabolism. This study was aimed at designing quantitative structure-activity relationship (QSAR) models for predicting toxic endpoints, namely cell viability and apoptosis, elicited by PBDEs in mammalian cells. Cell viability was evaluated quantitatively using a general cytotoxicity bioassay using Janus Green dye and apoptosis was evaluated using a caspase assay. This study has thus modelled the overall cytotoxic influence of PBDEs at an early and a late endpoint by the Genetic Function Approximation method. This research was a twofold process including running in vitro bioassays to collect data on the toxic endpoints and modeling the evaluated endpoints using QSARs. Cell viability and apoptosis responses for Hep G2 cells exposed to PBDEs were successfully modelled with an r(2) of 0.97 and 0.94, respectively.

  17. QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR OF VINCADIFFORMINE ANALOGUES AS THE ANTIPLASMODIAL COMPOUNDS OF THE CHLOROQUINOSENSIBLE STRAIN

    Directory of Open Access Journals (Sweden)

    Iqmal Tahir

    2010-06-01

    Full Text Available Quantitative Structure-Activity Relationship (QSAR analysis of vincadifformine analogs as an antimalarial drug has been conducted using atomic net charges (q, moment dipole (, LUMO (Lowest Unoccupied Molecular Orbital and HOMO (Highest Occupied Molecular Orbital energies, molecular mass (m as well as surface area (A as the predictors to their activity. Data of predictors are obtained from computational chemistry method using semi-empirical molecular orbital AM1 calculation. Antimalarial activities were taken as the activity of the drugs against chloroquine-sensitive Plasmodium falciparum (Nigerian Cell strain and were presented as the value of ln(1/IC50 where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best QSAR model has been determined by multiple linier regression analysis giving QSAR equation: Log (1/IC50 = 9.602.qC1 -17.012.qC2 +6.084.qC3 -19.758.qC5 -6.517.qC6 +2.746.qC7 -6.795.qN +6.59.qC8 -0.190. -0.974.ELUMO +0.515.EHOMO -0.274. +0.029.A -1.673 (n = 16; r = 0.995; SD = 0.099; F = 2.682   Keywords: QSAR analysis, antimalaria, vincadifformine.

  18. Structural Characterization and Evaluation of the Antioxidant Activity of Phenolic Compounds from Astragalus taipaishanensis and Their Structure-Activity Relationship

    Science.gov (United States)

    Pu, Wenjun; Wang, Dongmei; Zhou, Dan

    2015-09-01

    Eight phenolic compounds were isolated using bio-guided isolation and purified from the roots of Astragalus taipaishanensis Y. C. Ho et S. B. Ho (A. taipaishanensis) for the first time. Their structures were elucidated by ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR as 7,2‧-dihydroxy-3‧,4‧-dimethoxy isoflavan (1), formononetin (2), isoliquiritigenin (3), quercetin (4), kaempferol (5), ononin (6), p-hydroxybenzoic acid (7) and vanillic acid (8). Six flavonoids (compounds 1-6) exhibited stronger antioxidant activities (determined by DPPH, ABTS, FRAP and lipid peroxidation inhibition assays) than those of BHA and TBHQ and also demonstrated noticeable protective effects (particularly quercetin and kaempferol) on Escherichia coli under oxidative stress. Additionally, the chemical constituents compared with those of Astragalus membranaceus and the structure-activity relationship of the isolated compounds were both analyzed. The results clearly demonstrated that A. taipaishanensis has the potential to be selected as an alternative medicinal and food plant that can be utilized in health food products, functional tea and pharmaceutical products.

  19. Structure-activity relationship and mechanism of action studies of manzamine analogues for the control of neuroinflammation and cerebral infections.

    Science.gov (United States)

    Peng, Jiangnan; Kudrimoti, Sucheta; Prasanna, Sivaprakasam; Odde, Srinivas; Doerksen, Robert J; Pennaka, Hari K; Choo, Yeun-Mun; Rao, Karumanchi V; Tekwani, Babu L; Madgula, Vamsi; Khan, Shabana I; Wang, Bin; Mayer, Alejandro M S; Jacob, Melissa R; Tu, Lan Chun; Gertsch, Jürg; Hamann, Mark T

    2010-01-14

    Structure-activity relationship studies were carried out by chemical modification of manzamine A (1), 8-hydroxymanzamine A (2), manzamine F (14), and ircinal isolated from the sponge Acanthostrongylophora. The derived analogues were evaluated for antimalarial, antimicrobial, and antineuroinflammatory activities. Several modified products exhibited potent and improved in vitro antineuroinflammatory, antimicrobial, and antimalarial activity. 1 showed improved activity against malaria compared to chloroquine in both multi- and single-dose in vivo experiments. The significant antimalarial potential was revealed by a 100% cure rate of malaria in mice with one administration of 100 mg/kg of 1. The potent antineuroinflammatory activity of the manzamines will provide great benefit for the prevention and treatment of cerebral infections (e.g., Cryptococcus and Plasmodium). In addition, 1 was shown to permeate across the blood-brain barrier (BBB) in an in vitro model using a MDR-MDCK monolayer. Docking studies support that 2 binds to the ATP-noncompetitive pocket of glycogen synthesis kinase-3beta (GSK-3beta), which is a putative target of manzamines. On the basis of the results presented here, it will be possible to initiate rational drug design efforts around this natural product scaffold for the treatment of several different diseases.

  20. Selective kappa-opioid agonists: synthesis and structure-activity relationships of piperidines incorporating on oxo-containing acyl group.

    Science.gov (United States)

    Giardina, G; Clarke, G D; Dondio, G; Petrone, G; Sbacchi, M; Vecchietti, V

    1994-10-14

    This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2-(aminomethyl)piperidine derivatives, using kappa-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their kappa-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]-1-[(5,6,7,8-tetrahydro-5-oxo-2- naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 mumol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective kappa-agonists, has a reduced propensity to cause a number of kappa-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 mumol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.

  1. Design, synthesis and structure-activity relationships studies on the D ring of the natural product triptolide.

    Science.gov (United States)

    Xu, Hongtao; Tang, Huanyu; Feng, Huijin; Li, Yuanchao

    2014-02-01

    Triptolide is a diterpene triepoxide natural product isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal herb. Triptolide has previously been shown to possess antitumor, anti-inflammatory, immunosuppressive, and antifertility activities. Earlier reports suggested that the five-membered unsaturated lactone ring (D ring) is essential for potent cytotoxicity, however, to the best of our knowledge, systematic structure-activity relationship studies have not yet been reported. Here, four types of D ring-modified triptolide analogues were designed, synthesized and evaluated against human ovarian (SKOV-3) and prostate (PC-3) carcinoma cell lines. The results suggest that the D ring is essential to potency, however it can be modified, for example to C18 hydrogen bond acceptor and/or donor furan ring analogues, without complete loss of cytotoxic activity. Interestingly, evaluation of the key series of C19 analogues showed that this site is exquisitely sensitive to polarity. Together, these results will guide further optimization of this natural product lead compound for the development of potent and potentially clinically useful triptolide analogues. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Design, synthesis, and in vitro transfection biology of novel tocopherol based monocationic lipids: a structure-activity investigation.

    Science.gov (United States)

    Kedika, Bhavani; Patri, Srilakshmi V

    2011-01-27

    Herein, we report on the design, synthesis, and in vitro gene delivery efficacies of five novel tocopherol based cationic lipids (1-5) in transfecting CHO, B16F10, A-549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids (1-5) were evaluated by both β-galactosidase reporter gene expression and inverted fluorescent microscopic experiments. The results of the present structure-activity investigation convincingly demonstrate that the tocopherol based lipid with three hydroxyl groups in its headgroup region showed 4-fold better transfection efficiency than the commercial formulation. The results also demonstrate that these tocopherol based lipids may be targeted to liver. Transfection efficiency of all the relevant lipids was maintained even when the serum was present during the transfection conditions. The results indicated that the designed systems are quite capable of transferring the DNA into all four types of cells studied with low or no toxicity.

  3. Broad spectrum antibacterial and antifungal polymeric paint materials: synthesis, structure-activity relationship, and membrane-active mode of action.

    Science.gov (United States)

    Hoque, Jiaul; Akkapeddi, Padma; Yadav, Vikas; Manjunath, Goutham B; Uppu, Divakara S S M; Konai, Mohini M; Yarlagadda, Venkateswarlu; Sanyal, Kaustuv; Haldar, Jayanta

    2015-01-28

    Microbial attachment and subsequent colonization onto surfaces lead to the spread of deadly community-acquired and hospital-acquired (nosocomial) infections. Noncovalent immobilization of water insoluble and organo-soluble cationic polymers onto a surface is a facile approach to prevent microbial contamination. In the present study, we described the synthesis of water insoluble and organo-soluble polymeric materials and demonstrated their structure-activity relationship against various human pathogenic bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and beta lactam-resistant Klebsiella pneumoniae as well as pathogenic fungi such as Candida spp. and Cryptococcus spp. The polymer coated surfaces completely inactivated both bacteria and fungi upon contact (5 log reduction with respect to control). Linear polymers were more active and found to have a higher killing rate than the branched polymers. The polymer coated surfaces also exhibited significant activity in various complex mammalian fluids such as serum, plasma, and blood and showed negligible hemolysis at an amount much higher than minimum inhibitory amounts (MIAs). These polymers were found to have excellent compatibility with other medically relevant polymers (polylactic acid, PLA) and commercial paint. The cationic hydrophobic polymer coatings disrupted the lipid membrane of both bacteria and fungi and thus showed a membrane-active mode of action. Further, bacteria did not develop resistance against these membrane-active polymers in sharp contrast to conventional antibiotics and lipopeptides, thus the polymers hold great promise to be used as coating materials for developing permanent antimicrobial paint.

  4. Stereodivergent Synthesis of 1,3-Syn-Polyol Natural Product for Stereochemical-Based Structure Activity Relationship Studies

    Science.gov (United States)

    Zheng, Jiamin

    The 1,3-syn-diol functionality is very common in many natural products. An important class containing this moiety are the 1,3-syn-polyol/pyranone natural products, which have been isolated from a variety of plant sources, and possess biological activities like plant growth inhibition as well as antifeedant, antifungal, antibacterial, and antitumor properties. The feature of this class is a 6-membered lactone where the lactoe oxygen is part of a 1,3-syn-diol motif. To pursue the 1,3-syn-polyol/pyranone natural products, an iterative hydration of polyene strategy was utilized to provide the 1,3- syn-diol functionality, and asymmetric synthetic strategies were explored to form the requisite stereochemistry. The versatility of the asymmetric approach was demonstrated in the synthesis of eupatorium pyranone and also in an ongoing project aimed at the synthesis of SIA7248. As an outgrowth of our work on the total syntheses of 1,3-syn -polyol natural products inspired a stereo-divergent synthesis of 1,3-syn-polyol natural products and their analogs for stereochemical-based structure-activity relationship (SSAR) studies. To identify the key structural factors important for the anticancer activity of the 1,3-syn-polyol/pyranones, a stereo-divergent 16-member library of pyranone/polyol congeners was designed, synthesized and tested with variations in both stereochemistry and numbers of polyol repeat units. Having access to stereochemical isomers of the biologically active natural products allowed us to design experiments that help illustrate their mechanisms of action.

  5. Characteristics of chemical binding to alpha 2u-globulin in vitro--evaluating structure-activity relationships

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Miller, A.B.; Bowen, J.P.; Swenberg, J.A.

    1991-01-01

    alpha 2u-Globulin (alpha 2u) has been shown to accumulate in the kidneys of male rats treated with 2,2,4-trimethylpentane (TMP). 2,4,4-Trimethyl-2-pentanol (TMP-2-OH), a metabolite of TMP, is found reversibly bound to alpha 2u isolated from the kidneys of these treated rats. The objectives of the following study were to characterize the ability of [3H]TMP-2-OH to bind to alpha 2u in vitro and to determine whether other compounds that cause this protein to accumulate have the same binding characteristics. Although compounds that have been shown to cause the accumulation of alpha 2u in male rat kidneys compete in vitro with [3H]TMP-2-OH for binding to alpha 2u, they do so to varying degrees. The binding affinity (Kd) of the [3H]TMP-2-OH-alpha 2u complex was calculated to be on the order of 10(-7) M. The inhibition constant values (Ki) determined for d-limonene, 1,4-dichlorobenzene, and 2,5-dichlorophenol were all in the range 10(-4) M, whereas the Ki values for isophorone, 2,4,4- or 2,2,4-trimethyl-1-pentanol, and d-limonene oxide were determined to be in the range 10(-6) and 10(-7) M, respectively. TMP and 2,4,4- and 2,2,4-trimethylpentanoic acid did not compete for binding. This suggests that other factors, besides binding, are involved in the accumulation of alpha 2u. In this study the ability of a chemical to bind to alpha 2u was used as a measure of biological activity to assess structure-activity relationships among the chemicals tested and known to cause the accumulation of alpha 2u. The results so far suggest that binding is dependent on both hydrophobic interactions and hydrogen bonding

  6. Quantitative structure-activity relationship study of antioxidative peptide by using different sets of amino acids descriptors

    Science.gov (United States)

    Li, Yao-Wang; Li, Bo; He, Jiguo; Qian, Ping

    2011-07-01

    A database consisting of 214 tripeptides which contain either His or Tyr residue was applied to study quantitative structure-activity relationships (QSAR) of antioxidative tripeptides. Partial Least-Squares Regression analysis (PLSR) was conducted using parameters individually of each amino acid descriptor, including Divided Physico-chemical Property Scores (DPPS), Hydrophobic, Electronic, Steric, and Hydrogen (HESH), Vectors of Hydrophobic, Steric, and Electronic properties (VHSE), Molecular Surface-Weighted Holistic Invariant Molecular (MS-WHIM), isotropic surface area-electronic charge index (ISA-ECI) and Z-scale, to describe antioxidative tripeptides as X-variables and antioxidant activities measured with ferric thiocyanate methods were as Y-variable. After elimination of outliers by Hotelling's T 2 method and residual analysis, six significant models were obtained describing the entire data set. According to cumulative squared multiple correlation coefficients ( R2), cumulative cross-validation coefficients ( Q2) and relative standard deviation for calibration set (RSD c), the qualities of models using DPPS, HESH, ISA-ECI, and VHSE descriptors are better ( R2 > 0.6, Q2 > 0.5, RSD c 0.44). Furthermore, the predictive ability of models using DPPS descriptor is best among the six descriptors systems (cumulative multiple correlation coefficient for predict set ( Rext2) > 0.7). It was concluded that the DPPS is better to describe the amino acid of antioxidative tripeptides. The results of DPPS descriptor reveal that the importance of the center amino acid and the N-terminal amino acid are far more than the importance of the C-terminal amino acid for antioxidative tripeptides. The hydrophobic (positively to activity) and electronic (negatively to activity) properties of the N-terminal amino acid are suggested to play the most important significance to activity, followed by the hydrogen bond (positively to activity) of the center amino acid. The N-terminal amino acid

  7. The influence of R and S configurations of a series of amphetamine derivatives on quantitative structure-activity relationship models

    Energy Technology Data Exchange (ETDEWEB)

    Fresqui, Maira A.C., E-mail: maira@iqsc.usp.br [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil); Ferreira, Marcia M.C., E-mail: marcia@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, POB 6154, 13083-970 Campinas, SP (Brazil); Trsic, Milan, E-mail: cra612@gmail.com [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil)

    2013-01-08

    Highlights: Black-Right-Pointing-Pointer The QSAR model is not dependent of ligand conformation. Black-Right-Pointing-Pointer Amphetamines were analyzed by quantum chemical, steric and hydrophobic descriptors. Black-Right-Pointing-Pointer CHELPG atomic charges on the benzene ring are one of the most important descriptors. Black-Right-Pointing-Pointer The PLS models built were extensively validated. Black-Right-Pointing-Pointer Manual docking supports the QSAR results by pi-pi stacking interactions. - Abstract: Chiral molecules need special attention in drug design. In this sense, the R and S configurations of a series of thirty-four amphetamines were evaluated by quantitative structure-activity relationship (QSAR). This class of compounds has antidepressant, anti-Parkinson and anti-Alzheimer effects against the enzyme monoamine oxidase A (MAO A). A set of thirty-eight descriptors, including electronic, steric and hydrophobic ones, were calculated. Variable selection was performed through the correlation coefficients followed by the ordered predictor selection (OPS) algorithm. Six descriptors (CHELPG atomic charges C3, C4 and C5, electrophilicity, molecular surface area and log P) were selected for both configurations and a satisfactory model was obtained by PLS regression with three latent variables with R{sup 2} = 0.73 and Q{sup 2} = 0.60, with external predictability Q{sup 2} = 0.68, and R{sup 2} = 0.76 and Q{sup 2} = 0.67 with external predictability Q{sup 2} = 0.50, for R and S configurations, respectively. To confirm the robustness of each model, leave-N-out cross validation (LNO) was carried out and the y-randomization test was used to check if these models present chance correlation. Moreover, both automated or a manual molecular docking indicate that the reaction of ligands with the enzyme occurs via pi-pi stacking interaction with Tyr407, inclined face-to-face interaction with Tyr444, while aromatic hydrogen-hydrogen interactions with Tyr197 are preferable

  8. Discovery and preliminary structure-activity relationship of the marine natural product manzamines as herpes simplex virus type-1 inhibitors.

    Science.gov (United States)

    Palem, Jayavardhana R; Mudit, Mudit; Hsia, Shao-Chung V; Sayed, Khalid A El

    2017-01-01

    Herpes simplex virus type-1 (HSV-1) is a member of alpha-herpesviridae family and is known to cause contagious human infections. The marine habitat is a rich source of structurally unique bioactive secondary metabolites. A small library of marine natural product classes 1-10 has been screened to discover a new hit entity active against HSV-1. Manzamine A showed potent activity against HSV-1 via targeting the viral gene ICP0. Manzamine A is a β-carboline alkaloid isolated from the Indo-Pacific sponge Acanthostrongylophora species. Currently, acyclovir is the drug of choice for HSV-1 infections. Compared with 50 µM acyclovir, manzamine A at 1 µM concentration produced potent repressive effects on viral replication and release of infectious viruses in SIRC cells in recent studies. The potent anti-HSV-1 activity of manzamine A prompted a preliminary structure-activity relationship study by testing targeted manzamines. These included 8-hydroxymanzamine A (11), to test the effect of the C-8 hydroxy substitution at the β-carboline moiety; manzamine E (12), to assess the importance of substitution at the azacyclooctane ring; and ircinal A (13), to determine whether the β-carboline ring is required for the activity. Manzamine A was chemically transformed to its salt forms, manzamine A monohydrochloride (14) and manzamine A monotartrate (15), to test whether improving water solubility and hydrophilicity will positively affect the activity. Compounds were tested for activity against HSV-1 using fluorescent microscopy and plaque assay. The results showed the reduced anti-HSV-1 activity of 11, suggesting that C-8 hydroxy substitution might adversely affect the activity. Similarly, manzamines 12 and 13 showed no activity against HSV-1, indicating the preference of the unsubstituted azacylcooctane and β-carboline rings to the activity. Anti-HSV-1 activity was significantly improved for the manzamine A salts 14 and 15, suggesting that improving the overall water solubility

  9. Effect of O-methylated and glucuronosylated flavonoids from Tamarix gallica on α-glucosidase inhibitory activity: structure-activity relationship and synergistic potential.

    Science.gov (United States)

    Ben Hmidene, Asma; Smaoui, Abderrazak; Abdelly, Chedly; Isoda, Hiroko; Shigemori, Hideyuki

    2017-03-01

    O-Methylated and glucuronosylated flavonoids were isolated from Tamarix gallica as α-glucosidase inhibitors. Structure-activity relationship of these flavonoids suggests that catechol moiety and glucuronic acid at C-3 are factors in the increase in α-glucosidase inhibitory activity. Furthermore, rhamnetin, tamarixetin, rhamnazin, KGlcA, KGlcA-Me, QGlcA, and QGlcA-Me exhibit synergistic potential when applied with a very low concentration of acarbose to α-glucosidase from rat intestine.

  10. Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.

    Science.gov (United States)

    Hu, Yi; Ma, Lifu; Wu, Min; Wong, Melissa S; Li, Bei; Corral, Sergio; Yu, Zhizhou; Nomanbhoy, Tyzoon; Alemayehu, Senaiet; Fuller, Stacy R; Rosenblum, Jonathan S; Rozenkrants, Natasha; Minimo, Lauro C; Ripka, William C; Szardenings, Anna K; Kozarich, John W; Shreder, Kevin R

    2005-10-01

    The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

  11. Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

    Science.gov (United States)

    Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

    2002-01-07

    A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

  12. Synthesis and structure-activity relationship of the first nonpeptidergic inverse agonists for the human cytomegalovirus encoded chemokine receptor US28.

    Science.gov (United States)

    Hulshof, Janneke W; Casarosa, Paola; Menge, Wiro M P B; Kuusisto, Leena M S; van der Goot, Henk; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

    2005-10-06

    US28 is a human cytomegalovirus (HCMV) encoded G-protein-coupled receptor that signals in a constitutively active manner. Recently, we identified 1 [5-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2,2-diphenylpentanenitrile] as the first reported nonpeptidergic inverse agonist for a viral-encoded chemokine receptor. Interestingly, this compound is able to partially inhibit the viral entry of HIV-1. In this study we describe the synthesis of 1 and several of its analogues and unique structure-activity relationships for this first class of small-molecule ligands for the chemokine receptor US28. Moreover, the compounds have been pharmacologically characterized as inverse agonists on US28. By modification of lead structure 1, it is shown that a 4-phenylpiperidine moiety is essential for affinity and activity. Other structural features of 1 are shown to be of less importance. These compounds define the first SAR of ligands on a viral GPCR (US28) and may therefore serve as important tools to investigate the significance of US28-mediated constitutive activity during viral infection.

  13. Structure-activity relationship studies of 1,7-diheteroarylhepta-1,4,6-trien-3-ones with two different terminal rings in prostate epithelial cell models.

    Science.gov (United States)

    Wang, Rubing; Zhang, Xiaojie; Chen, Chengsheng; Chen, Guanglin; Sarabia, Cristian; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong

    2017-06-16

    To systematically investigate the structure-activity relationships of 1,7-diheteroarylhepta-1,4,6-trien-3-ones in three human prostate cancer cell models and one human prostate non-neoplastic epithelial cell model, thirty five 1,7-diarylhepta-1,4,6-trien-3-ones with different terminal heteroaromatic rings have been designed for evaluation of their anti-proliferative potency in vitro. These target compounds have been successfully synthesized through two sequential Horner-Wadsworth-Emmons reactions starting from the appropriate aldehydes and tetraethyl (2-oxopropane-1,3-diyl)bis(phosphonate). Their anti-proliferative potency against PC-3, DU-145 and LNCaP human prostate cancer cell lines can be significantly enhanced by the manipulation of the terminal heteroaromatic rings, further demonstrating the utility of 1,7-diarylhepta-1,4,6-trien-3-one as a potential scaffold for the development of anti-prostate cancer agents. The optimal analog 40 is 82-, 67-, and 39-fold more potent than curcumin toward the three prostate cancer cell lines, respectively. The experimental data also reveal that the trienones with two different terminal aromatic rings possess greater potency toward three prostate cancer cell lines, but also have greater capability of suppressing the proliferation of PWR-1E benign human prostate epithelial cells, as compared to the corresponding counterparts with two identical terminal rings and curcumin. The terminal aromatic rings also affect the cell apoptosis perturbation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Effects of heterocyclic-based head group modifications on the structure-activity relationship of tocopherol-based lipids for non-viral gene delivery.

    Science.gov (United States)

    Gosangi, Mallikarjun; Mujahid, Thasneem Yoosuf; Gopal, Vijaya; Patri, Srilakshmi V

    2016-07-12

    Gene therapy, a promising strategy for the delivery of therapeutic nucleic acids, is greatly dependent on the development of efficient vectors. In this study, we designed and synthesized several tocopherol-based lipids varying in the head group region. Here, we present the structure-activity relationship of stable aqueous suspensions of lipids that were synthetically prepared and formulated with 1,2-dioleoyl phosphatidyl ethanolamine (DOPE) as the co-lipid. The physicochemical properties such as the hydrodynamic size, zeta potential, stability and morphology of these formulations were investigated. Interaction with plasmid DNA was clearly demonstrated through gel binding and EtBr displacement assays. Further, the transfection potential was examined in mouse neuroblastoma Neuro-2a, hepatocarcinoma HepG2, human embryonic kidney and Chinese hamster ovarian cell lines, all of different origins. Cell-uptake assays with N-methylpiperidinium, N-methylmorpholinium, N-methylimidazolium and N,N-dimethylaminopyridinium head group containing formulations evidently depicted efficient cell uptake as observed by particulate cytoplasmic fluorescence. Trafficking of lipoplexes using an endocytic marker and rhodamine-labeled phospholipid DHPE indicated that the lipoplexes were not sequestered in the lysosomes. Importantly, lipoplexes were non-toxic and mediated good transfection efficiency as analyzed by β-Gal and GFP reporter gene expression assays which established the superior activity of lipids whose structures correlate strongly with the transfection efficiency.

  15. Investigation of structure-activity relationships of Oxyntomodulin (Oxm) using Oxm analogs.

    Science.gov (United States)

    Druce, Maralyn R; Minnion, James S; Field, Benjamin C T; Patel, Sejal R; Shillito, Joyceline C; Tilby, Michael; Beale, Kylie E L; Murphy, Kevin G; Ghatei, Mohammad A; Bloom, Stephen R

    2009-04-01

    Oxyntomodulin (Oxm) is an intestinal peptide that inhibits food intake and body weight in rodents and humans. These studies used peptide analogs to study aspects of structure and function of Oxm, and the sensitivity of parts of the Oxm sequence to degradation. Analogs of Oxm were synthesized and studied using receptor binding and degradation studies in vitro. Their effects on food intake and conditioned taste avoidance were measured in vivo in rodents. Oxm breakdown by the enzyme dipeptidyl peptidase IV (DPPIV) was demonstrated in vitro and in vivo. In vitro degradation was reduced and in vivo bioactivity increased by inhibitors of DPPIV. Modifications to the N terminus of Oxm modulated binding to the glucagon-like peptide (GLP)-1 receptor and degradation by DPPIV. Modifications to the midsection of Oxm modulated binding to the GLP-1 receptor and degradation by neutral endopeptidase. These modifications also altered bioactivity in vivo. The C-terminal octapeptide of Oxm was shown to contribute to the properties of Oxm in vitro and in vivo but was not alone sufficient for the effects of the peptide. Elongation and acylation of the C terminus of Oxm altered GLP-1 receptor binding and duration of action in vivo, which may be due to changes in peptide clearance. An Oxm analog was developed with enhanced pharmaceutical characteristics, with greater potency and longevity with respect to effects on food intake. These studies suggest that Oxm is a potential target for antiobesity drug design.

  16. Investigating the relationship between social responsibility and ...

    African Journals Online (AJOL)

    Investigating the relationship between social responsibility and improving organizational commitment in employees of Tehran Ghavamin Bank with respect to the mediating role of psychological empowerment.

  17. Structure determination of glycogen synthase kinase-3 from Leishmania major and comparative inhibitor structure-activity relationships with Trypanosoma brucei GSK-3

    Energy Technology Data Exchange (ETDEWEB)

    Ojo, Kayode K; Arakaki, Tracy L; Napuli, Alberto J; Inampudi, Krishna K; Keyloun, Katelyn R; Zhang, Li; Hol, Wim G.J.; Verlind, Christophe L.M.J.; Merritt, Ethan A; Van Voorhis, Wesley C [UWASH

    2012-04-24

    Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation in pharmaceutical companies and constitutes an attractive piggyback target for eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about 150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has previously been validated genetically as a drug target in Trypanosoma brucei by RNAi induced growth retardation; and chemically by correlation between enzyme and in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3 short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270, identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of LmajGSK-3 short at 2 Å resolution. The inhibitor structure-activity relationships (SARs) of L. major and L. infantum are virtually identical, suggesting that inhibitors could be useful for both cutaneous and visceral leishmaniasis. Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short, which can be explained mostly by two variant residues in the ATP-binding pocket. Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR more similar to that of TbruGSK-3 short. The differences between human GSK-3β (HsGSK-3β) and LmajGSK-3 short SAR suggest that compounds which selectively inhibit LmajGSK-3 short may be found.

  18. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size : Structure-activity relationships of non-digestible oligosaccharides.

    Science.gov (United States)

    Akbari, Peyman; Fink-Gremmels, Johanna; Willems, Rianne H A M; Difilippo, Elisabetta; Schols, Henk A; Schoterman, Margriet H C; Garssen, Johan; Braber, Saskia

    2017-08-01

    The direct effects of galacto-oligosaccharides (GOS), including Vivinal ® GOS syrup (VGOS) and purified Vivinal ® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure-activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin. Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA. In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release. This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

  19. Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.

    Science.gov (United States)

    Perucca, Paola; Savio, Monica; Cazzalini, Ornella; Mocchi, Roberto; Maccario, Cristina; Sommatis, Sabrina; Ferraro, Daniela; Pizzala, Roberto; Pretali, Luca; Fasani, Elisa; Albini, Angelo; Stivala, Lucia Anna

    2014-11-01

    The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O₂ partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Development of quantitative structure activity relationship (QSAR) model for disinfection byproduct (DBP) research: A review of methods and resources

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Baiyang, E-mail: poplar_chen@hotmail.com [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China); Zhang, Tian [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China); Bond, Tom [Department of Civil and Environmental Engineering, Imperial College, London SW7 2AZ (United Kingdom); Gan, Yiqun [Harbin Institute of Technology Shenzhen Graduate School, Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Shenzhen 518055 (China)

    2015-12-15

    Quantitative structure–activity relationship (QSAR) models are tools for linking chemical activities with molecular structures and compositions. Due to the concern about the proliferating number of disinfection byproducts (DBPs) in water and the associated financial and technical burden, researchers have recently begun to develop QSAR models to investigate the toxicity, formation, property, and removal of DBPs. However, there are no standard procedures or best practices regarding how to develop QSAR models, which potentially limit their wide acceptance. In order to facilitate more frequent use of QSAR models in future DBP research, this article reviews the processes required for QSAR model development, summarizes recent trends in QSAR-DBP studies, and shares some important resources for QSAR development (e.g., free databases and QSAR programs). The paper follows the four steps of QSAR model development, i.e., data collection, descriptor filtration, algorithm selection, and model validation; and finishes by highlighting several research needs. Because QSAR models may have an important role in progressing our understanding of DBP issues, it is hoped that this paper will encourage their future use for this application.

  1. Development of quantitative structure activity relationship (QSAR) model for disinfection byproduct (DBP) research: A review of methods and resources

    International Nuclear Information System (INIS)

    Chen, Baiyang; Zhang, Tian; Bond, Tom; Gan, Yiqun

    2015-01-01

    Quantitative structure–activity relationship (QSAR) models are tools for linking chemical activities with molecular structures and compositions. Due to the concern about the proliferating number of disinfection byproducts (DBPs) in water and the associated financial and technical burden, researchers have recently begun to develop QSAR models to investigate the toxicity, formation, property, and removal of DBPs. However, there are no standard procedures or best practices regarding how to develop QSAR models, which potentially limit their wide acceptance. In order to facilitate more frequent use of QSAR models in future DBP research, this article reviews the processes required for QSAR model development, summarizes recent trends in QSAR-DBP studies, and shares some important resources for QSAR development (e.g., free databases and QSAR programs). The paper follows the four steps of QSAR model development, i.e., data collection, descriptor filtration, algorithm selection, and model validation; and finishes by highlighting several research needs. Because QSAR models may have an important role in progressing our understanding of DBP issues, it is hoped that this paper will encourage their future use for this application.

  2. Dopamine D(3) receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans.

    Science.gov (United States)

    Haadsma-Svensson, S R; Cleek, K A; Dinh, D M; Duncan, J N; Haber, C L; Huff, R M; Lajiness, M E; Nichols, N F; Smith, M W; Svensson, K A; Zaya, M J; Carlsson, A; Lin, C H

    2001-12-20

    5,6-Dimethoxy-2-(N-dipropyl)-aminoindan (3, PNU-99194A) was found to be a selective dopamine D(3) receptor antagonist with potential antipsychotic properties in animal models. To investigate the effects of nitrogen substitution on structure-activity relationships, a series of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans were synthesized and evaluated in vitro for binding affinity and metabolic stability. The results indicate that substitution at the amine nitrogen of the 2-aminoindans is fairly limited to the di-N-propyl group in order to achieve selective D(3) antagonists. Thus, combinations of various alkyl groups were generally inactive at the D(3) receptor. Although substitution with an N-alkylaryl or N-alkylheteroaryl group yields compounds with potent D(3) binding affinity, the D(2) affinity is also enhanced, resulting in a less than 4-fold preference for the D(3) receptor site, and no improvements in metabolic stability were noted. A large-scale synthesis of the D(3) antagonist 3 has been developed that has proven to be reproducible with few purification steps. The improvements include the use of 3,4-dimethoxybenzaldehyde as a low-cost starting material to provide the desired 5,6-dimethoxy-1-indanone 5c in good overall yield (65%) and the formation of a soluble silyl oxime 17 that was reduced efficiently with BH(3).Me(2)S. The resulting amino alcohol was alkylated and then deoxygenated using a Lewis acid and Et(3)SiH to give the desired product 3 in good overall yield of ( approximately 65%) from the indanone 5c.

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

    Directory of Open Access Journals (Sweden)

    Jerzy Leszczynski

    2000-10-01

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

  4. Structure-activity relationship of the ionic cocrystal: 5-amino-2-naphthalene sulfonate·ammonium ions for pharmaceutical applications

    Science.gov (United States)

    Sangeetha, M.; Mathammal, R.

    2018-02-01

    The ionic cocrystals of 5-amino-2-naphthalene sulfonate · ammonium ions (ANSA-ṡNH4+) were grown under slow evaporation method and examined in detail for pharmaceutical applications. The crystal structure and intermolecular interactions were studied from the single X-ray diffraction analysis and the Hirshfeld surfaces. The 2D fingerprint plots displayed the inter-contacts possible in the ionic crystal. Computational DFT method was established to determine the structural, physical and chemical properties. The molecular geometries obtained from the X-ray studies were compared with the optimized geometrical parameters calculated using DFT/6-31 + G(d,p) method. The band gap energy calculated from the UV-Visible spectral analysis and the HOMO-LUMO energy gap are compared. The theoretical UV-Visible calculations helped in determining the type of electronic transition taking place in the title molecule. The maximum absorption bands and transitions involved in the molecule represented the drug reaction possible. Non-linear optical properties were characterized from SHG efficiency measurements experimentally and the NLO parameters are also calculated from the optimized structure. The reactive sites within the molecule are detailed from the MEP surface maps. The molecular docking studies evident the structure-activity of the ionic cocrystal for anti-cancer drug property.

  5. Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

    Science.gov (United States)

    Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

    2015-07-15

    Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Structure-activity relationship of prenyl-substituted polyphenols from Artocarpus heterophyllus as inhibitors of melanin biosynthesis in cultured melanoma cells.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2007-09-01

    A series of prenylated, flavone-based polyphenols, compounds 1-8, were isolated from the wood of Artocarpus heterophyllus. These compounds, which have previously been shown not to inhibit tyrosinase activity, were found to be active inhibitors of the in vivo melanin biosynthesis in B16 melanoma cells, with little or no cytotoxicity. To clarify the structural requirement for inhibition, some structure-activity relationships were studied, in comparison with related compounds lacking prenyl side chains. Our experiments indicate that both prenyl and OH groups, as well as the type of substitution pattern, are crucial for the inhibition of melanin production in B16 melanoma cells.

  7. Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

    Science.gov (United States)

    Argade, Ankush; Bhamidipati, Somasekhar; Li, Hui; Carroll, David; Clough, Jeffrey; Keim, Holger; Sylvain, Catherine; Rossi, Alexander B; Coquilla, Christina; Issakani, Sarkiz D; Masuda, Esteban S; Payan, Donald G; Singh, Rajinder

    2015-01-01

    Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives: Synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery.

    Science.gov (United States)

    Quiliano, Miguel; Pabón, Adriana; Moles, Ernest; Bonilla-Ramirez, Leonardo; Fabing, Isabelle; Fong, Kim Y; Nieto-Aco, Diego A; Wright, David W; Pizarro, Juan C; Vettorazzi, Ariane; López de Cerain, Adela; Deharo, Eric; Fernández-Busquets, Xavier; Garavito, Giovanny; Aldana, Ignacio; Galiano, Silvia

    2018-05-25

    Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC 50 s activity in chloroquine-sensitive and multidrug-resistant strains (IC 50 s antimalarial compounds. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  9. PLS-based quantitative structure-activity relationship for substituted benzamides of clebopride type. Application of experimental design in drug design.

    Science.gov (United States)

    Norinder, U; Högberg, T

    1992-04-01

    The advantageous approach of using an experimentally designed training set as the basis for establishing a quantitative structure-activity relationship with good predictive capability is described. The training set was selected from a fractional factorial design scheme based on a principal component description of physico-chemical parameters of aromatic substituents. The derived model successfully predicts the activities of additional substituted benzamides of 6-methoxy-N-(4-piperidyl)salicylamide type. The major influence on activity of the 3-substituent is demonstrated.

  10. Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A role played by the lactone moiety.

    Science.gov (United States)

    Qiu, Haibo; Qian, Shan; Head, Sarah A; Liu, Jun O; Jin, Zhendong

    2016-10-01

    Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, a new analog ZJ-109 was designed and synthesized to probe the importance of the lactone moiety of the molecule by replacing the lactone in ZJ-101 with a lactam. The biological evaluation showed that ZJ-109 is about 8-12 times less active against cancer cells in vitro than ZJ-101, suggesting that the lactone moiety of the molecule is important for its anticancer activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Modeling Chemical Interaction Profiles: I. Spectral Data-Activity Relationship and Structure-Activity Relationship Models for Inhibitors and Non-inhibitors of Cytochrome P450 CYP3A4 and CYP2D6 Isozymes

    OpenAIRE

    McPhail, Brooks; Tie, Yunfeng; Hong, Huixiao; Pearce, Bruce A.; Schnackenberg, Laura K.; Ge, Weigong; Valerio, Luis G.; Fuscoe, James C.; Tong, Weida; Buzatu, Dan A.; Wilkes, Jon G.; Fowler, Bruce A.; Demchuk, Eugene; Beger, Richard D.

    2012-01-01

    An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals—drugs, pesticides, and environmental pollutants—interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP) enzymes. In the present work, spectral data-activity relationship (SDAR) and structure-activity relationship (SAR) approaches were used to develop machine-learning classifi...

  12. Quantitative structure-activity relationship (QSAR) models for polycyclic aromatic hydrocarbons (PAHs) dissipation in rhizosphere based on molecular structure and effect size

    International Nuclear Information System (INIS)

    Ma Bin; Chen Huaihai; Xu Minmin; Hayat, Tahir; He Yan; Xu Jianming

    2010-01-01

    Rhizoremediation is a significant form of bioremediation for polycyclic aromatic hydrocarbons (PAHs). This study examined the role of molecular structure in determining the rhizosphere effect on PAHs dissipation. Effect size in meta-analysis was employed as activity dataset for building quantitative structure-activity relationship (QSAR) models and accumulative effect sizes of 16 PAHs were used for validation of these models. Based on the genetic algorithm combined with partial least square regression, models for comprehensive dataset, Poaceae dataset, and Fabaceae dataset were built. The results showed that information indices, calculated as information content of molecules based on the calculation of equivalence classes from the molecular graph, were the most important molecular structural indices for QSAR models of rhizosphere effect on PAHs dissipation. The QSAR model, based on the molecular structure indices and effect size, has potential to be used in studying and predicting the rhizosphere effect of PAHs dissipation. - Effect size based on meta-analysis was used for building PAHs dissipation quantitative structure-activity relationship (QSAR) models.

  13. Quantitative structure-activity relationship (QSAR) models for polycyclic aromatic hydrocarbons (PAHs) dissipation in rhizosphere based on molecular structure and effect size

    Energy Technology Data Exchange (ETDEWEB)

    Ma Bin; Chen Huaihai; Xu Minmin; Hayat, Tahir [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China); He Yan, E-mail: yhe2006@zju.edu.c [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China); Xu Jianming, E-mail: jmxu@zju.edu.c [Zhejiang Provincial Key Laboratory of Subtropical Soil and Plant Nutrition, College of Environmental and Natural Resource Sciences, Zhejiang University, Hangzhou 310029 (China)

    2010-08-15

    Rhizoremediation is a significant form of bioremediation for polycyclic aromatic hydrocarbons (PAHs). This study examined the role of molecular structure in determining the rhizosphere effect on PAHs dissipation. Effect size in meta-analysis was employed as activity dataset for building quantitative structure-activity relationship (QSAR) models and accumulative effect sizes of 16 PAHs were used for validation of these models. Based on the genetic algorithm combined with partial least square regression, models for comprehensive dataset, Poaceae dataset, and Fabaceae dataset were built. The results showed that information indices, calculated as information content of molecules based on the calculation of equivalence classes from the molecular graph, were the most important molecular structural indices for QSAR models of rhizosphere effect on PAHs dissipation. The QSAR model, based on the molecular structure indices and effect size, has potential to be used in studying and predicting the rhizosphere effect of PAHs dissipation. - Effect size based on meta-analysis was used for building PAHs dissipation quantitative structure-activity relationship (QSAR) models.

  14. Quantitative structure-activity relationship analysis to elucidate the clearance mechanisms of Tc-99m labeled quinolone antibiotics

    International Nuclear Information System (INIS)

    Salahinejad, M.; Mirshojaei, S.F.

    2016-01-01

    This study aims to establish molecular modeling methods for predicting the liver and kidney uptakes of Tc-99m labeled quinolone antibiotics. Some three-dimensional quantitative-activity relationships (3D-QSAR) models were developed using comparative molecular field analysis and grid-independent descriptors procedures. As a first report on 3D-QSAR modeling, the predicted liver and kidney uptakes for quinolone antibiotics were in good agreement with the experimental values. The obtained results confirm the importance of hydrophobic interactions, size and steric hindrance of antibiotic molecules in their liver uptakes, while the electrostatic interactions and hydrogen bonding ability have impressive effects on their kidney uptakes. (author)

  15. Effect of green tea catechins and hydrolyzable tannins on benzo[a]pyrene-induced DNA adducts and structure-activity relationship.

    Science.gov (United States)

    Cao, Pengxiao; Cai, Jian; Gupta, Ramesh C

    2010-04-19

    Green tea catechins and hydrolyzable tannins are gaining increasing attention as chemopreventive agents. However, their mechanism of action is poorly understood. We investigated the effects of four green tea catechins and two hydrolyzable tannins on microsome-induced benzo[a]pyrene (BP)-DNA adducts and the possible structure-activity relationship. BP (1 microM) was incubated with rat liver microsomes and DNA in the presence of the test compound (1-200 microM) or vehicle. The purified DNA was analyzed by (32)P-postlabeling. The inhibitory activity of the catechins was in the following descending order: epigallocatechin gallate (IC(50) = 16 microM) > epicatechin gallate (24 microM) > epigallocatechin (146 microM) > epicatechin (462 microM), suggesting a correlation between the number of adjacent aromatic hydroxyl groups in the molecular structure and their potencies. Tannic acid (IC(50) = 4 microM) and pentagalloglucose (IC(50) = 26 microM) elicited as much DNA adduct inhibitory activity as the catechins or higher presumably due to the presence of more functional hydroxyl groups. To determine if the activity of these compounds was due to direct interaction of phenolic groups with electrophilic metabolite(s) of BP, DNA was incubated with anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) (0.5 microM) in the presence of test compounds (200 microM) or vehicle. Significant inhibition of DNA adduct formation was found (tannic acid > pentagalloglucose > epigallocatechin gallate > epicatechin gallate). This notion was confirmed by analysis of the reaction products of anti-BPDE with the catechins and pentagalloglucose by electrospray ionization mass spectrometry and liquid chromatography-mass spectrometry. In conclusion, our data demonstrate that green tea catechins and the hydrolyzable tannins are highly effective in inhibiting BP-DNA adduct formation at least, in part, due to direct interaction of adjacent hydroxyl groups in their structures and that the activity is

  16. Optimization of triazine nitriles as rhodesain inhibitors: structure-activity relationships, bioisosteric imidazopyridine nitriles, and X-ray crystal structure analysis with human cathepsin L.

    Science.gov (United States)

    Ehmke, Veronika; Winkler, Edwin; Banner, David W; Haap, Wolfgang; Schweizer, W Bernd; Rottmann, Matthias; Kaiser, Marcel; Freymond, Céline; Schirmeister, Tanja; Diederich, François

    2013-06-01

    The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 substituent led to high-affinity ligands with inhibition constants down to 2 nM for compounds bearing cyclohexyl substituents. Systematic investigations on the S3 pocket revealed its potential to achieve high activities with aromatic vectors that undergo stacking interactions with the planar peptide backbone forming part of the pocket. X-ray crystal structure analysis with the structurally related enzyme human cathepsin L confirmed the binding mode of the triazine ligand series as proposed by molecular modeling. Sub-micromolar inhibition of the proliferation of cultured parasites was achieved for ligands decorated with the best substituents identified through the optimization cycles. In cell-based assays, the introduction of a basic side chain on the inhibitors resulted in a 35-fold increase in antitrypanosomal activity. Finally, bioisosteric imidazopyridine nitriles were studied in order to prevent off-target effects with unselective nucleophiles by decreasing the inherent electrophilicity of the triazine nitrile headgroup. Using this ligand, the stabilization by intramolecular hydrogen bonding of the thioimidate intermediate, formed upon attack of the catalytic cysteine residue, compensates for the lower reactivity of the headgroup. The imidazopyridine nitrile ligand showed

  17. Structure-Activity Relationship Study of Sesquiterpene Lactones and Their Semi-Synthetic Amino Derivatives as Potential Antitrypanosomal Products

    Directory of Open Access Journals (Sweden)

    Stefanie Zimmermann

    2014-03-01

    Full Text Available Sesquiterpene lactones (STLs are natural products that have potent antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce parasitemia in the murine model of trypanosomiasis. To explore their structure-antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes East African sleeping sickness and mammalian cancer cells (rat bone myoblast L6 cells. It was found that the α-methylene-γ-lactone moiety is necessary for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity is facilitated by 2-(hydroxymethylacrylate or 3,4-dihydroxy-2-methylenebutylate side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL amines with morpholino and dimethylamino groups showed improved in vitro activity over the native STLs. The dimethylamino derivative of cynaropicrin was prepared and tested orally in the T. b. rhodesiense acute mouse model, where it showed reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity.

  18. Quantitative structure activity relationships (QSAR) for binary mixtures at non-equitoxic ratios based on toxic ratios-effects curves.

    Science.gov (United States)

    Tian, Dayong; Lin, Zhifen; Yin, Daqiang

    2013-01-01

    The present study proposed a QSAR model to predict joint effects at non-equitoxic ratios for binary mixtures containing reactive toxicants, cyanogenic compounds and aldehydes. Toxicity of single and binary mixtures was measured by quantifying the decrease in light emission from the Photobacterium phosphoreum for 15 min. The joint effects of binary mixtures (TU sum) can thus be obtained. The results showed that the relationships between toxic ratios of the individual chemicals and their joint effects can be described by normal distribution function. Based on normal distribution equations, the joint effects of binary mixtures at non-equitoxic ratios ( [Formula: see text]) can be predicted quantitatively using the joint effects at equitoxic ratios ( [Formula: see text]). Combined with a QSAR model of [Formula: see text]in our previous work, a novel QSAR model can be proposed to predict the joint effects of mixtures at non-equitoxic ratios ( [Formula: see text]). The proposed model has been validated using additional mixtures other than the one used for the development of the model. Predicted and observed results were similar (p>0.05). This study provides an approach to the prediction of joint effects for binary mixtures at non-equitoxic ratios.

  19. Kinetics and structure-activity relationship of dendritic bridged hindered phenol antioxidants to protect styrene against free radical induced peroxidation

    Science.gov (United States)

    Li, Cui-Qin; Guo, Su-Yue; Wang, Jun; Shi, Wei-Guang; Zhang, Zhi-Qiu; Wang, Peng-Xiang

    2017-12-01

    A series of dendritic poly(amido-amine) (PAMAM) bridged hindered phenols antioxidants were synthesized. The active antioxidant group (3-(3,5-di- tert-butyl-4-hydroxyphenyl)propionic acid) was attached to two generations of PAMAM dendrimers, and their structure was verified by nuclear magnetic resonance (NMR) and fourier transform infrared spectra (FT-IR). The antioxidant abilities of the dendritic phenols to inhibit the oxidation of styrene were evaluated and the relationships between the length of core, the generation of dendrimers and the antioxidant activities were established. The reaction kinetics of scavenging peroxyl radicals was followed by oxygen consumption. The inhibition time ( t inh) values showed the dendritic phenols had the ability of scavenging peroxyl radicals, and that the antioxidant ability increased with the increasing length of the core and the generation. The kinetic analysis demonstrated that dendritic phenols could slow the rate of styrene peroxidation induced by AIBN, as shown by the number of trapping ROO· ( n), and this role was in accordance with that of the t inh values.

  20. Identification of phototransformation products of thalidomide and mixture toxicity assessment: an experimental and quantitative structural activity relationships (QSAR) approach.

    Science.gov (United States)

    Mahmoud, Waleed M M; Toolaram, Anju P; Menz, Jakob; Leder, Christoph; Schneider, Mandy; Kümmerer, Klaus

    2014-02-01

    The fate of thalidomide (TD) was investigated after irradiation with a medium-pressure Hg-lamp. The primary elimination of TD was monitored and structures of phototransformation products (PTPs) were assessed by LC-UV-FL-MS/MS. Environmentally relevant properties of TD and its PTPs as well as hydrolysis products (HTPs) were predicted using in silico QSAR models. Mutagenicity of TD and its PTPs was investigated in the Ames microplate format (MPF) aqua assay (Xenometrix, AG). Furthermore, a modified luminescent bacteria test (kinetic luminescent bacteria test (kinetic LBT)), using the luminescent bacteria species Vibrio fischeri, was applied for the initial screening of environmental toxicity. Additionally, toxicity of phthalimide, one of the identified PTPs, was investigated separately in the kinetic LBT. The UV irradiation eliminated TD itself without complete mineralization and led to the formation of several PTPs. TD and its PTPs did not exhibit mutagenic response in the Salmonella typhimurium strains TA 98, and TA 100 with and without metabolic activation. In contrast, QSAR analysis of PTPs and HTPs provided evidence for mutagenicity, genotoxicity and carcinogenicity using additional endpoints in silico software. QSAR analysis of different ecotoxicological endpoints, such as acute toxicity towards V. fischeri, provided positive alerts for several identified PTPs and HTPs. This was partially confirmed by the results of the kinetic LBT, in which a steady increase of acute and chronic toxicity during the UV-treatment procedure was observed for the photolytic mixtures at the highest tested concentration. Moreover, the number of PTPs within the reaction mixture that might be responsible for the toxification of TD during UV-treatment was successfully narrowed down by correlating the formation kinetics of PTPs with QSAR predictions and experimental toxicity data. Beyond that, further analysis of the commercially available PTP phthalimide indicated that transformation of

  1. The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships.

    Science.gov (United States)

    Shaghafi, Michael B; Barrett, David G; Willard, Francis S; Overman, Larry E

    2014-02-15

    We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Structure-activity relationship study of oxindole-based inhibitors of cyclin-dependent kinases based on least-squares support vector machines

    International Nuclear Information System (INIS)

    Li Jiazhong; Liu Huanxiang; Yao Xiaojun; Liu Mancang; Hu Zhide; Fan Botao

    2007-01-01

    The least-squares support vector machines (LS-SVMs), as an effective modified algorithm of support vector machine, was used to build structure-activity relationship (SAR) models to classify the oxindole-based inhibitors of cyclin-dependent kinases (CDKs) based on their activity. Each compound was depicted by the structural descriptors that encode constitutional, topological, geometrical, electrostatic and quantum-chemical features. The forward-step-wise linear discriminate analysis method was used to search the descriptor space and select the structural descriptors responsible for activity. The linear discriminant analysis (LDA) and nonlinear LS-SVMs method were employed to build classification models, and the best results were obtained by the LS-SVMs method with prediction accuracy of 100% on the test set and 90.91% for CDK1 and CDK2, respectively, as well as that of LDA models 95.45% and 86.36%. This paper provides an effective method to screen CDKs inhibitors

  3. Seamless integration of dose-response screening and flow chemistry: efficient generation of structure-activity relationship data of β-secretase (BACE1) inhibitors.

    Science.gov (United States)

    Werner, Michael; Kuratli, Christoph; Martin, Rainer E; Hochstrasser, Remo; Wechsler, David; Enderle, Thilo; Alanine, Alexander I; Vogel, Horst

    2014-02-03

    Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure-activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a flow-based biochemical assay and its seamless integration into a fully automated system comprising flow chemical synthesis, purification and in-line quantification of compound concentration. This novel synthesis-screening platform enables to obtain SAR data on b-secretase (BACE1) inhibitors at an unprecedented cycle time of only 1 h instead of several days. Full integration and automation of industrial processes have always led to productivity gains and cost reductions, and this work demonstrates how applying these concepts to SAR generation may lead to a more efficient drug discovery process. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Structure-Activity Relationship Study of N(6)-Benzoyladenine-Type BRD4 Inhibitors and Their Effects on Cell Differentiation and TNF-α Production.

    Science.gov (United States)

    Amemiya, Seika; Yamaguchi, Takao; Sakai, Taki; Hashimoto, Yuichi; Noguchi-Yachide, Tomomi

    2016-01-01

    Bromodomains are epigenetic 'readers' of histone acetylation. The first potent bromodomain and extra-terminal domain (BET) inhibitors, (+)-JQ1 and I-BET762 (also known as GSK525762), were reported in 2010. Some BET inhibitors are already under clinical trial for the treatment of cancers, but so far, only a few chemical scaffolds are available. We have reported potent N(6)-benzoyladenine-based inhibitors of BRD4, a BET family member that serves as a key mediator of transcriptional elongation. Here we present an analysis of the structure-activity relationships of these inhibitors. Among the compounds examined, 20, 28 and 29 enhanced all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation and inhibited tumor necrosis factor (TNF)-α production by THP-1 cells.

  5. Antimitotic antitumor agents: synthesis, structure-activity relationships, and biological characterization of N-aryl-N'-(2-chloroethyl)ureas as new selective alkylating agents.

    Science.gov (United States)

    Mounetou, E; Legault, J; Lacroix, J; C-Gaudreault, R

    2001-03-01

    A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl ring or a fluorenyl/indanyl group, (ii) an exocyclic urea function, and (iii) a N'-2-chloroethyl moiety were required to ensure significant cytotoxicity. Biological experiments, such as immunofluorescence microscopy, confirmed that these promising compounds alter the cytoskeleton by inducing microtubule depolymerization via selective alkylation of beta-tubulin. Subsequent evaluations demonstrated that potent CEUs were weak alkylators, were non-DNA-damaging agents, and did not interact with the thiol function of either glutathione or glutathione reductase. Therefore, CEUs are part of a new class of antimitotic agents. Finally, among the series of CEUs evaluated, compounds 12, 15, 16, and 27 were selected for further in vivo trials.

  6. Inhibition of 125I-labeled ristocetin binding to Micrococcus luteus cells by the peptides related to bacterial cell wall mucopeptide precursors: quantitative structure-activity relationships

    International Nuclear Information System (INIS)

    Kim, K.H.; Martin, Y.; Otis, E.; Mao, J.

    1989-01-01

    Quantitative structure-activity relationships (QSAR) of N-Ac amino acids, N-Ac dipeptides, and N-Ac tripeptides in inhibition of 125 I-labeled ristocetin binding to Micrococcus luteus cell wall have been developed to probe the details of the binding between ristocetin and N-acetylated peptides. The correlation equations indicate that (1) the binding is stronger for peptides in which the side chain of the C-terminal amino acid has a large molar refractivity (MR) value, (2) the binding is weaker for peptides with polar than for those with nonpolar C-terminal side chains, (3) the N-terminal amino acid in N-Ac dipeptides contributes 12 times that of the C-terminal amino acid to binding affinity, and (4) the interactions between ristocetin and the N-terminal amino acid of N-acetyl tripeptides appear to be much weaker than those with the first two amino acids

  7. Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides.

    Science.gov (United States)

    Du, Shijie; Tian, Zaimin; Yang, Dongyan; Li, Xiuyun; Li, Hong; Jia, Changqing; Che, Chuanliang; Wang, Mian; Qin, Zhaohai

    2015-05-08

    A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

  8. Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

    Directory of Open Access Journals (Sweden)

    Shijie Du

    2015-05-01

    Full Text Available A series of novel 3-(difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-ylphenyl-3-(difluoro-methyl-1-methyl-1H-pyrazole-4-carboxamide (9m exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

  9. Structure-Activity Relationship Study on the Ethyl p-Methoxycinnamate as an Anti-Inflammatory Agent

    Directory of Open Access Journals (Sweden)

    Ismiarni Komala

    2018-02-01

    Full Text Available Ethyl p-methoxycinnamate (EPMC (1 has been isolated as a major compound from the rhizome of Kaempferia galanga together with the other compound ethyl cinnamate (2. As reported in the literature, EPMC (1 exhibited a significant in vitro and in vivo anti-inflammatory activity. In this research, we investigated the anti-inflammatory activity of compounds 1 and 2 by using anti-denaturation of heat bovine serum albumin (BSA method. In order to analyze active sites that are responsible for the anti-inflammatory activity, therefore, it is necessary to conduct structural modification of EPMC (1. The structural modification was performed through re-esterification reaction by using conventional and assistance of the unmodified microwave oven. Evaluation of the results of the bioassay indicated that the ester and methoxy functional groups of EPMC (1 play an important role for the anti-inflammatory activity.

  10. Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei

    Directory of Open Access Journals (Sweden)

    Stefano Fiorucci

    2012-11-01

    Full Text Available Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present.

  11. Structure-activity relationships of new cyanothiophene inhibitors of the essential peptidoglycan biosynthesis enzyme MurF.

    Science.gov (United States)

    Hrast, Martina; Turk, Samo; Sosič, Izidor; Knez, Damijan; Randall, Christopher P; Barreteau, Hélène; Contreras-Martel, Carlos; Dessen, Andréa; O'Neill, Alex J; Mengin-Lecreulx, Dominique; Blanot, Didier; Gobec, Stanislav

    2013-08-01

    Peptidoglycan is an essential component of the bacterial cell wall, and enzymes involved in its biosynthesis represent validated targets for antibacterial drug discovery. MurF catalyzes the final intracellular peptidoglycan biosynthesis step: the addition of D-Ala-D-Ala to the nucleotide precursor UDP-MurNAc-L-Ala-γ-D-Glu-meso-DAP (or L-Lys). As MurF has no human counterpart, it represents an attractive target for the development of new antibacterial drugs. Using recently published cyanothiophene inhibitors of MurF from Streptococcus pneumoniae as a starting point, we designed and synthesized a series of structurally related derivatives and investigated their inhibition of MurF enzymes from different bacterial species. Systematic structural modifications of the parent compounds resulted in a series of nanomolar inhibitors of MurF from S. pneumoniae and micromolar inhibitors of MurF from Escherichia coli and Staphylococcus aureus. Some of the inhibitors also show antibacterial activity against S. pneumoniae R6. These findings, together with two new co-crystal structures, represent an excellent starting point for further optimization toward effective novel antibacterials. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

    Science.gov (United States)

    Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

    2016-01-01

    We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

  13. Investigating the relationship between knowledge management and ...

    African Journals Online (AJOL)

    The purpose of current study is to investigate the relationship between knowledge management and employees' empowerment in Agriculture Bank of Tehran Province. Method is descriptive-survey and correlation type. Statistical population of the research is all employees of Agriculture Bank in Tehran that are 2800 ...

  14. Investigating the relationship between Malaysian rugby sevens ...

    African Journals Online (AJOL)

    The objective of this study is is to investigate the relationship between rugbgby match officials physical fitness to their perfor formance. 132 rugby side match official seven wewere selected as the respondent of the study. ANOANOVA indicated no significant differences [F = (3, 128) = 0.322, p = 0.809] in physical fitness ac ...

  15. Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species

    Directory of Open Access Journals (Sweden)

    Chiara Cheng Lim

    2009-03-01

    Full Text Available DNA damage by reactive species is associated with susceptibility to chronic human degenerative disorders. Anthocyanins are naturally occurring antioxidants, that may prevent or reverse such damage. There is considerable interest in anthocyanic food plants as good dietary sources, with the potential for reducing susceptibility to chronic disease. While structure-activity relationships have provided guidelines on molecular structure in relation to free hydroxyl- radical scavenging, this may not cover the situation in food plants where the anthocyanins are part of a complex mixture, and may be part of complex structures, including anthocyanic vacuolar inclusions (AVIs. Additionally, new analytical methods have revealed new structures in previously-studied materials. We have compared the antioxidant activities of extracts from six anthocyanin-rich edible plants (red cabbage, red lettuce, blueberries, pansies, purple sweetpotato skin, purple sweetpotato flesh and Maori potato flesh using three chemical assays (DPPH, TRAP and ORAC, and the in vitro Comet assay. Extracts from the flowering plant, lisianthus, were used for comparison. The extracts showed differential effects in the chemical assays, suggesting that closely related structures have different affinities to scavenge different reactive species. Integration of anthocyanins to an AVI led to more sustained radical scavenging activity as compared with the free anthocyanin. All but the red lettuce extract could reduce endogenous DNA damage in HT-29 colon cancer cells. However, while extracts from purple sweetpotato skin and flesh, Maori potato and pansies, protected cells against subsequent challenge by hydrogen peroxide at 0oC, red cabbage extracts were pro-oxidant, while other extracts had no effect. When the peroxide challenge was at 37oC, all of the extracts appeared pro-oxidant. Maori potato extract, consistently the weakest antioxidant in all the chemical assays, was more effective in the

  16. Polybrominated diphenyl ether (PBDE) effects in rat neuronal cultures: 14C-PBDE accumulation, biological effect, and structure-activity relationships

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, P.R.; Ward, T. [Neurotoxicology Div., NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Burka, T. [National Insts. of Environmental Health Sciences, Research Triangle Park, NC (United States); Ludewig, G.; Robertson, L. [The Univ. of Iowa Coll. of Public Health, Iowa City, IA (United States); Birnbaum, L. [Experimental Toxicology Div., NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2004-09-15

    Polybrominated diphenyl ethers (PBDEs) are used as flame-retardants in many types of consumer products such as electrical equipment, plastics, and building materials. PBDEs are structurally similar to dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs). PBDEs are now ubiquitous; they can be found in air, water, fish, birds, marine mammals, and humans, and in many cases, they are increasing over time. In spite of their widespread occurrence in the environment, only limited information is available on the toxicology of PBDEs. Recent studies showed that PBDE exposure caused aberrations in spontaneous behavior and reduced learning and memory in mice these effects are similar to those seen after exposure to DDT or PCBs. However, the mode of action for this group of chemicals remains unclear. Previously, we demonstrated that PCBs, which are known to cause neurotoxic effects, affected intracellular signaling pathways including [{sup 3}H]arachidonic acid ([{sup 3}H]AA) release, calcium homeostasis, and translocation of protein kinase C (PKC). Regarding PBDEs, we have reported that PBDEs altered [{sup 3}H]AA release in neuronal cultures like PCBs. These signaling pathways have been associated with learning and memory, and the development of the nervous system. The objectives of the present study were to test: (a) whether biologically relevant PBDE congeners affected PKC translocation in neuronal cultures in a similar way to those of other organohalogens; (b) compare the potency and efficacy of PBDE congeners with their 14C-accumulation; and (c) understand the structure-activity relationships among PBDE congeners.

  17. Discovery, synthesis, and structure-activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2β1γ1 activators.

    Science.gov (United States)

    Liu, Junhua; Chen, Dakai; Liu, Peng; He, Mengna; Li, Jia; Li, Jingya; Hu, Lihong

    2014-05-22

    Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype α2β1γ1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure-activity relationship study showed that the amine derivatives at the 24-position (groups I-VI) can improve the potency (EC50: 0.7-2.3 μM) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 1.2 and 0.7 μM) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Three-dimensional quantitative structure-activity relationships and docking studies of some structurally diverse flavonoids and design of new aldose reductase inhibitors

    Directory of Open Access Journals (Sweden)

    Utpal Chandra De

    2015-01-01

    Full Text Available Aldose reductase (AR plays an important role in the development of several long-term diabetic complications. Inhibition of AR activities is a strategy for controlling complications arising from chronic diabetes. Several AR inhibitors have been reported in the literature. Flavonoid type compounds are shown to have significant AR inhibition. The objective of this study was to perform a computational work to get an idea about structural insight of flavonoid type compounds for developing as well as for searching new flavonoid based AR inhibitors. The data-set comprising 68 flavones along with their pIC 50 values ranging from 0.44 to 4.59 have been collected from literature. Structure of all the flavonoids were drawn in Chembiodraw Ultra 11.0, converted into corresponding three-dimensional structure, saved as mole file and then imported to maestro project table. Imported ligands were prepared using LigPrep option of maestro 9.6 version. Three-dimensional quantitative structure-activity relationships and docking studies were performed with appropriate options of maestro 9.6 version installed in HP Z820 workstation with CentOS 6.3 (Linux. A model with partial least squares factor 5, standard deviation 0.2482, R 2 = 0.9502 and variance ratio of regression 122 has been found as the best statistical model.

  19. Structure-activity relationship study of Aib-containing amphipathic helical peptide-cyclic RGD conjugates as carriers for siRNA delivery.

    Science.gov (United States)

    Wada, Shun-Ichi; Takesada, Anna; Nagamura, Yurie; Sogabe, Eri; Ohki, Rieko; Hayashi, Junsuke; Urata, Hidehito

    2017-12-15

    The conjugation of Aib-containing amphipathic helical peptide with cyclo(-Arg-Gly-Asp-d-Phe-Cys-) (cRGDfC) at the C-terminus of the helix peptide (PI) has been reported to be useful for constructing a carrier for targeted siRNA delivery into cells. In order to explore structure-activity relationships for the development of potential carriers for siRNA delivery, we synthesized conjugates of Aib-containing amphipathic helical peptide with cRGDfC at the N-terminus (PII) and both the N- and C-termini (PIII) of the helical peptide. Furthermore, to examine the influence of PI helical chain length on siRNA delivery, truncated peptides containing 16 (PIV), 12 (PV), and 8 (PVI) amino acid residues at the N-terminus of the helical chain were synthesized. PII and PIII, as well as PI, could deliver anti-luciferase siRNA into cells to induce the knockdown of luciferase stably expressed in cells. In contrast, all of the truncated peptides were unlikely to transport siRNA into cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Linear and non-linear quantitative structure-activity relationship models on indole substitution patterns as inhibitors of HIV-1 attachment.

    Science.gov (United States)

    Nirouei, Mahyar; Ghasemi, Ghasem; Abdolmaleki, Parviz; Tavakoli, Abdolreza; Shariati, Shahab

    2012-06-01

    The antiviral drugs that inhibit human immunodeficiency virus (HIV) entry to the target cells are already in different phases of clinical trials. They prevent viral entry and have a highly specific mechanism of action with a low toxicity profile. Few QSAR studies have been performed on this group of inhibitors. This study was performed to develop a quantitative structure-activity relationship (QSAR) model of the biological activity of indole glyoxamide derivatives as inhibitors of the interaction between HIV glycoprotein gp120 and host cell CD4 receptors. Forty different indole glyoxamide derivatives were selected as a sample set and geometrically optimized using Gaussian 98W. Different combinations of multiple linear regression (MLR), genetic algorithms (GA) and artificial neural networks (ANN) were then utilized to construct the QSAR models. These models were also utilized to select the most efficient subsets of descriptors in a cross-validation procedure for non-linear log (1/EC50) prediction. The results that were obtained using GA-ANN were compared with MLR-MLR and MLR-ANN models. A high predictive ability was observed for the MLR, MLR-ANN and GA-ANN models, with root mean sum square errors (RMSE) of 0.99, 0.91 and 0.67, respectively (N = 40). In summary, machine learning methods were highly effective in designing QSAR models when compared to statistical method.

  2. Antitumor potential of crown ethers: structure-activity relationships, cell cycle disturbances, and cell death studies of a series of ionophores.

    Science.gov (United States)

    Marjanović, Marko; Kralj, Marijeta; Supek, Fran; Frkanec, Leo; Piantanida, Ivo; Smuc, Tomislav; Tusek-Bozić, Ljerka

    2007-03-08

    The present paper demonstrates the antiproliferative ability and structure-activity relationships (SAR) of 14 crown and aza-crown ether analogues on five tumor-cell types. The most active compounds were di-tert-butyldicyclohexano-18-crown-6 (3), which exhibited cytotoxicity in the submicromolar range, and di-tert-butyldibenzo-18-crown-6 (5) (IC50 values of approximately 2 microM). Also, 3 and 5 induced marked influence on the cell cycle phase distribution--strong G1 arrest, followed by the induction of apoptosis. A computational SAR modeling effort offers insight into possible mechanisms of crown ether biological activity, presumably involving penetration into cell membranes, and points out structural features of molecules important for this activity. The results reveal that crown ethers possess marked tumor-cell growth inhibitory activity, the extent of which depends on the characteristics of the hydrophilic macrocylic cavity and the surrounding hydrophobic ring. Our work supports the hypothesis that crown ether compounds inhibit tumor-cell growth by disrupting potassium ion homeostasis, which in turn leads to cell cycle perturbations and apoptosis.

  3. Effects of synthetic and naturally occurring flavonoids on Na+, K+-ATPase: Aspects of the structure-activity relationship and action mechanism

    International Nuclear Information System (INIS)

    Hirano, T.; Oka, K.; Akiba, M.

    1989-01-01

    A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na + , K + -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na + , K + -ATPase from dog kidney cortex when present at concentrations from 40-1000 μM. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC 50 at 257-320 μM. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one much-gt 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one > 2-cyclohexyl-6-hydroxy-benzopyran-4-one > 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block [ 3 H] ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na + , K + -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme

  4. Studies on Synthesis and Structure-Activity Relationship (SAR of Derivatives of a New Natural Product from Marine Fungi as Inhibitors of Influenza Virus Neuraminidase

    Directory of Open Access Journals (Sweden)

    Yongcheng Lin

    2011-10-01

    Full Text Available Based on the natural isoprenyl phenyl ether from a mangrove-derived fungus, 32 analogues were synthesized and evaluated for inhibitory activity against influenza H1N1 neuraminidase. Compound 15 (3-(allyloxy-4-hydroxybenzaldehyde exhibited the most potent inhibitory activity, with IC50 values of 26.96 μM for A/GuangdongSB/01/2009 (H1N1, 27.73 μM for A/Guangdong/03/2009 (H1N1, and 25.13 μM for A/Guangdong/05/2009 (H1N1, respectively, which is stronger than the benzoic acid derivatives (~mM level. These are a new kind of non-nitrogenous aromatic ether Neuraminidase (NA inhibitors. Their structures are simple and the synthesis routes are not complex. The structure-activity relationship (SAR analysis revealed that the aryl aldehyde and unsubstituted hydroxyl were important to NA inhibitory activities. Molecular docking studies were carried out to explain the SAR of the compounds, and provided valuable information for further structure modification.

  5. Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid

    DEFF Research Database (Denmark)

    Krogsgaard-Larsen, Niels; Storgaard, Morten; Møller, Charlotte

    2015-01-01

    Herein we describe the first structure-activity relationship study of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5' positions and the bioisosteric substitution of the distal...... carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4' position 2a which induced a preference in binding affinity for homomeric GluK3 over GluK1 (Ki = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: 2e in GluA2-LBD...... and 2f in GluK1-LBD, both at 1.9 Å resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8° and 2f a domain opening in GluK1-LBD of 17.0-17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f shows a similar binding mode as kainate...

  6. In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

    International Nuclear Information System (INIS)

    Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaelle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Francoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Veronique; Dufrasne, Francois; Van Antwerpen, Pierre; Poumay, Yves

    2011-01-01

    The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.

  7. Quantitative Structure-Activity Relationships Predicting the Antioxidant Potency of 17β-Estradiol-Related Polycyclic Phenols to Inhibit Lipid Peroxidation

    Directory of Open Access Journals (Sweden)

    Katalin Prokai-Tatrai

    2013-01-01

    Full Text Available The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order to relate their molecular structure and properties with their capacity to inhibit lipid peroxidation, a marker of oxidative stress, quantitative structure-activity relationship (QSAR studies were conducted. The inhibition of Fe3+-induced lipid peroxidation in rat brain homogenate, measured through an assay detecting thiobarbituric acid reactive substances for about seventy compounds were correlated with various molecular descriptors. We found that lipophilicity (modeled by the logarithm of the n-octanol/water partition coefficient, logP was the property that influenced most profoundly the potency of these compounds to inhibit lipid peroxidation in the biological medium studied. Additionally, the important contribution of the bond dissociation enthalpy of the phenolic O-H group, a shape index, the solvent-accessible surface area and the energy required to remove an electron from the highest occupied molecular orbital were also confirmed. Several QSAR equations were validated as potentially useful exploratory tools for identifying or designing novel phenolic antioxidants incorporating the structural backbone of 17β-estradiol to assist therapy development against oxidative stress-associated neurodegeneration.

  8. Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability

    Directory of Open Access Journals (Sweden)

    Chen-Peng Chen

    2018-04-01

    Full Text Available The skin permeability (Kp defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical’s skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone.

  9. Structure-activity relationships of dimethylsphingosine (DMS) derivatives and their effects on intracellular pH and Ca2+ in the U937 monocyte cell line.

    Science.gov (United States)

    Chang, Young-Ja; Lee, Yun-Kyung; Lee, Eun-Hee; Park, Jeong-Ju; Chung, Sung-Kee; Im, Dong-Soon

    2006-08-01

    We recently reported that dimethylsphingosine (DMS), a metabolite of sphingolipids, increased intracellular pH and Ca2+ concentration in U937 human monocytes. In the present study, we found that dimethylphytosphingosine (DMPH) induced the above responses more robustly than DMS. However, phytosphingosine, monomethylphytosphingosine or trimethylsphingosine showed little or no activity. Synthetic C3 deoxy analogues of sphingosine did show similar activities, with the C16 analogue more so than C18. The following structure-activity relationships were observed between DMS derivatives and the intracellular pH and Ca2+ concentrations in U937 monocytes; 1) dimethyl modification is important for the DMS-induced increase of intracellular pH and Ca2+, 2) the addition of an OH group on C4 enhances both activities, 3) the deletion of the OH group on C3 has a negligible effect on the activities, and 4) C16 appears to be more effective than C18. We also found that W-7, a calmodulin inhibitor, blocked the DMS-induced pH increase, whereas, KN-62, ML9, and MMPX, specific inhibitors for calmodulin-dependent kinase II, myosin light chain kinase, and Ca(2+)-calmodulin-dependent phosphodiesterase, respectively, did not affect DMS-induced increases of pH in the U937 monocytes.

  10. Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid.

    Science.gov (United States)

    Martínez-Gualda, Belén; Sun, Liang; Rivero-Buceta, Eva; Flores, Aida; Quesada, Ernesto; Balzarini, Jan; Noppen, Sam; Liekens, Sandra; Schols, Dominique; Neyts, Johan; Leyssen, Pieter; Mirabelli, Carmen; Camarasa, María-José; San-Félix, Ana

    2017-03-01

    We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a "decarboxylated" analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Biochemical interpretation of quantitative structure-activity relationships (QSAR) for biodegradation of N-heterocycles: a complementary approach to predict biodegradability.

    Science.gov (United States)

    Philipp, Bodo; Hoff, Malte; Germa, Florence; Schink, Bernhard; Beimborn, Dieter; Mersch-Sundermann, Volker

    2007-02-15

    Prediction of the biodegradability of organic compounds is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. We combined quantitative structure-activity relationships (QSAR) with the systematic collection of biochemical knowledge to establish rules for the prediction of aerobic biodegradation of N-heterocycles. Validated biodegradation data of 194 N-heterocyclic compounds were analyzed using the MULTICASE-method which delivered two QSAR models based on 17 activating (OSAR 1) and on 16 inactivating molecular fragments (GSAR 2), which were statistically significantly linked to efficient or poor biodegradability, respectively. The percentages of correct classifications were over 99% for both models, and cross-validation resulted in 67.9% (GSAR 1) and 70.4% (OSAR 2) correct predictions. Biochemical interpretation of the activating and inactivating characteristics of the molecular fragments delivered plausible mechanistic interpretations and enabled us to establish the following biodegradation rules: (1) Target sites for amidohydrolases and for cytochrome P450 monooxygenases enhance biodegradation of nonaromatic N-heterocycles. (2) Target sites for molybdenum hydroxylases enhance biodegradation of aromatic N-heterocycles. (3) Target sites for hydratation by an urocanase-like mechanism enhance biodegradation of imidazoles. Our complementary approach represents a feasible strategy for generating concrete rules for the prediction of biodegradability of organic compounds.

  12. A New Structure-Activity Relationship (SAR) Model for Predicting Drug-Induced Liver Injury, Based on Statistical and Expert-Based Structural Alerts

    Science.gov (United States)

    Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Benfenati, Emilio

    2016-01-01

    The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model. To extract structural alerts (SAs) related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC) on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81, 63, and 68%, specificity 89, 33, and 33%, sensitivity 93, 88, and 80% and MCC 0.63, 0.27, and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model's architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform. PMID:27920722

  13. A new structure-activity relationship (SAR model for predicting drug-induced liver injury, based on statistical and expert-basedstructural alerts.

    Directory of Open Access Journals (Sweden)

    Fabiola Pizzo

    2016-11-01

    Full Text Available The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80% and test sets (20%. We also compiled an external validation set (101 compounds for evaluating the performance of the model. To extract structural alerts (SAs related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81%, 63% and 68%, specificity 89%, 33% and 33%, sensitivity 93%, 88% and 80% and MCC 0.63, 0.27 and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model’s architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform.

  14. ICI 56,780 Optimization: Structure-Activity Relationship Studies of 7-(2-Phenoxyethoxy)-4(1H)-quinolones with Antimalarial Activity.

    Science.gov (United States)

    Maignan, Jordany R; Lichorowic, Cynthia L; Giarrusso, James; Blake, Lynn D; Casandra, Debora; Mutka, Tina S; LaCrue, Alexis N; Burrows, Jeremy N; Willis, Paul A; Kyle, Dennis E; Manetsch, Roman

    2016-07-28

    Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.

  15. Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus.

    Science.gov (United States)

    Li, Sumei; Jia, Xiuhua; Shen, Xintian; Wei, Zhuwen; Jiang, Zhiyan; Liao, Yixian; Guo, Yiming; Zheng, Xiaojun; Zhong, Guohua; Song, Gaopeng

    2017-08-15

    Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC 50 values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Lipid A structural modifications in extreme conditions and identification of unique modifying enzymes to define the Toll-like receptor 4 structure-activity relationship.

    Science.gov (United States)

    Scott, Alison J; Oyler, Benjamin L; Goodlett, David R; Ernst, Robert K

    2017-11-01

    Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant. A limited 'toolbox' of lipid A-modifying enzymes has been defined and is largely composed of enzymes from mesophile human and zoonotic pathogens. Expansion of this 'toolbox' will result from extending the search into lipid A biosynthesis and modification by bacteria living at the extremes. Here, we review the fundamentals of lipid A structure, advances in lipid A uses in TLR4 modulation, and the search for novel lipid A-modifying systems in extremophile bacteria. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Effects of synthetic and naturally occurring flavonoids on Na sup + , K sup + -ATPase: Aspects of the structure-activity relationship and action mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, T.; Oka, K.; Akiba, M. (Tokyo College of Pharmacy (Japan))

    1989-01-01

    A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na{sup +}, K{sup +} -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na{sup +}, K{sup +} -ATPase from dog kidney cortex when present at concentrations from 40-1000 {mu}M. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC{sub 50} at 257-320 {mu}M. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one {much gt} 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one {gt} 2-cyclohexyl-6-hydroxy-benzopyran-4-one {gt} 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block ({sup 3}H) ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na{sup +}, K{sup +} -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme.

  18. Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin.

    Science.gov (United States)

    Liu, Tao; Ma, Ming; Ge, Hui-Ming; Yang, Chunying; Cleveland, John; Shen, Ben

    2015-11-01

    Leinamycin (LNM, 1) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4'-dideshydroxy-LNM (5) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1; 5 exhibits comparable activity as 1 with the EC50 values between 8.21 and 275 nM. This work reveals new insight into the structure-activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

    Science.gov (United States)

    Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

    2017-02-22

    Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

  20. Structure-Activity Relationships of New Natural Product-Based Diaryloxazoles with Selective Activity against Androgen Receptor-Positive Breast Cancer Cells.

    Science.gov (United States)

    Robles, Andrew J; McCowen, Shelby; Cai, Shengxin; Glassman, Michaels; Ruiz, Francisco; Cichewicz, Robert H; McHardy, Stanton F; Mooberry, Susan L

    2017-11-22

    Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC. Bioassay-guided fractionation identified two oxazole natural products with selective activity against this cell line. Conducted analog synthesis and structure-activity relationship studies provided analogs with more potent and selective activity against two LAR subtype cell line models, culminating in the discovery of compound 30 (CIDD-0067106). Lead compounds discovered have potent and selective antiproliferative activities, and mechanisms of action studies show they inhibit the activity of the mTORC1 pathway.

  1. Evaluating Molecular Properties Involved in Transport of Small Molecules in Stratum Corneum: A Quantitative Structure-Activity Relationship for Skin Permeability.

    Science.gov (United States)

    Chen, Chen-Peng; Chen, Chan-Cheng; Huang, Chia-Wen; Chang, Yen-Ching

    2018-04-15

    The skin permeability ( Kp ) defines the rate of a chemical penetrating across the stratum corneum. This value is widely used to quantitatively describe the transport of molecules in the outermost layer of epidermal skin and indicate the significance of skin absorption. This study defined a Kp quantitative structure-activity relationship (QSAR) based on 106 chemical substances of Kp measured using human skin and interpreted the molecular interactions underlying transport behavior of small molecules in the stratum corneum. The Kp QSAR developed in this study identified four molecular descriptors that described the molecular cyclicity in the molecule reflecting local geometrical environments, topological distances between pairs of oxygen and chlorine atoms, lipophilicity, and similarity to antineoplastics in molecular properties. This Kp QSAR considered the octanol-water partition coefficient to be a direct influence on transdermal movement of molecules. Moreover, the Kp QSAR identified a sub-domain of molecular properties initially defined to describe the antineoplastic resemblance of a compound as a significant factor in affecting transdermal permeation of solutes. This finding suggests that the influence of molecular size on the chemical's skin-permeating capability should be interpreted with other relevant physicochemical properties rather than being represented by molecular weight alone.

  2. 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.

  3. Hydrogen Production by Ethanol Steam Reforming (ESR over CeO2 Supported Transition Metal (Fe, Co, Ni, Cu Catalysts: Insight into the Structure-Activity Relationship

    Directory of Open Access Journals (Sweden)

    Michalis Konsolakis

    2016-03-01

    Full Text Available The aim of the present work was to investigate steam reforming of ethanol with regard to H2 production over transition metal catalysts supported on CeO2. Various parameters concerning the effect of temperature (400–800 °C, steam-to-carbon (S/C feed ratio (0.5, 1.5, 3, 6, metal entity (Fe, Co, Ni, Cu and metal loading (15–30 wt.% on the catalytic performance, were thoroughly studied. The optimal performance was obtained for the 20 wt.% Co/CeO2 catalyst, achieving a H2 yield of up to 66% at 400 °C. In addition, the Co/CeO2 catalyst demonstrated excellent stability performance in the whole examined temperature range of 400–800 °C. In contrast, a notable stability degradation, especially at low temperatures, was observed for Ni-, Cu-, and Fe-based catalysts, ascribed mainly to carbon deposition. An extensive characterization study, involving N2 adsorption-desorption (BET, X-ray diffraction (XRD, Scanning Electron Microscopy (SEM/EDS, X-ray Photoelectron Spectroscopy (XPS, and Temperature Programmed Reduction (H2-TPR was undertaken to gain insight into the structure-activity correlation. The excellent reforming performance of Co/CeO2 catalysts could be attributed to their intrinsic reactivity towards ethanol reforming in combination to their high surface oxygen concentration, which hinders the deposition of carbonaceous species.

  4. Three-dimensional quantitative structure-activity relationship (3D QSAR) and pharmacophore elucidation of tetrahydropyran derivatives as serotonin and norepinephrine transporter inhibitors

    Science.gov (United States)

    Kharkar, Prashant S.; Reith, Maarten E. A.; Dutta, Aloke K.

    2008-01-01

    Three-dimensional quantitative structure-activity relationship (3D QSAR) using comparative molecular field analysis (CoMFA) was performed on a series of substituted tetrahydropyran (THP) derivatives possessing serotonin (SERT) and norepinephrine (NET) transporter inhibitory activities. The study aimed to rationalize the potency of these inhibitors for SERT and NET as well as the observed selectivity differences for NET over SERT. The dataset consisted of 29 molecules, of which 23 molecules were used as the training set for deriving CoMFA models for SERT and NET uptake inhibitory activities. Superimpositions were performed using atom-based fitting and 3-point pharmacophore-based alignment. Two charge calculation methods, Gasteiger-Hückel and semiempirical PM3, were tried. Both alignment methods were analyzed in terms of their predictive abilities and produced comparable results with high internal and external predictivities. The models obtained using the 3-point pharmacophore-based alignment outperformed the models with atom-based fitting in terms of relevant statistics and interpretability of the generated contour maps. Steric fields dominated electrostatic fields in terms of contribution. The selectivity analysis (NET over SERT), though yielded models with good internal predictivity, showed very poor external test set predictions. The analysis was repeated with 24 molecules after systematically excluding so-called outliers (5 out of 29) from the model derivation process. The resulting CoMFA model using the atom-based fitting exhibited good statistics and was able to explain most of the selectivity (NET over SERT)-discriminating factors. The presence of -OH substituent on the THP ring was found to be one of the most important factors governing the NET selectivity over SERT. Thus, a 4-point NET-selective pharmacophore, after introducing this newly found H-bond donor/acceptor feature in addition to the initial 3-point pharmacophore, was proposed.

  5. Structure-activity relationships for flavone interactions with amyloid β reveal a novel anti-aggregatory and neuroprotective effect of 2',3',4'-trihydroxyflavone (2-D08).

    Science.gov (United States)

    Marsh, Dylan T; Das, Sukanya; Ridell, Jessica; Smid, Scott D

    2017-07-15

    Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid β (Aβ). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aβ protein. In the present study we have characterised the Aβ binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Quercetin, transilitin, jaceosidin, nobiletin and 2-D08 were incubated with human Aβ 1-42 for 48h in vitro and effects on Aβ fibrillisation kinetics and morphology measured using Thioflavin T (ThT) and electron microscopy respectively, in addition to effects on neuronal PC12 cell viability. Of the flavones studied, only quercetin, transilitin and 2-D08 significantly inhibited Aβ 1-42 aggregation and toxicity in PC12 cells. Of those, 2-D08 was the most effective inhibitor. The strong anti-amyloid activity of 2-D08 indicates that extensive hydroxylation in the B ring is the most important determinant of activity against β amyloid within the flavone scaffold. The lack of efficacy of jaceosidin and nobiletin indicate that extension of B ring hydroxylation with methoxyl groups result in an incremental loss of anti-fibrillar and neuroprotective activity, highlighting the constraint to vicinal hydroxyl groups in the B ring for effective inhibition of aggregation. These findings reveal further structural insights into anti-amyloid bioactivity of flavonoids in addition to a novel and efficacious anti-aggregatory and neuroprotective effect of the semi-synthetic flavone and sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Such modified flavones may facilitate drug development targeting multiple pathways in neurodegenerative disease. Crown Copyright © 2017

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

    Science.gov (United States)

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

    2015-02-01

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

  7. An orientation sensitive approach in biomolecule interaction quantitative structure-activity relationship modeling and its application in ion-exchange chromatography.

    Science.gov (United States)

    Kittelmann, Jörg; Lang, Katharina M H; Ottens, Marcel; Hubbuch, Jürgen

    2017-01-27

    Quantitative structure-activity relationship (QSAR) modeling for prediction of biomolecule parameters has become an established technique in chromatographic purification process design. Unfortunately available descriptor sets fail to describe the orientation of biomolecules and the effects of ionic strength in the mobile phase on the interaction with the stationary phase. The literature describes several special descriptors used for chromatographic retention modeling, all of these do not describe the screening of electrostatic potential by the mobile phase in use. In this work we introduce two new approaches of descriptor calculations, namely surface patches and plane projection, which capture an oriented binding to charged surfaces and steric hindrance of the interaction with chromatographic ligands with regard to electrostatic potential screening by mobile phase ions. We present the use of the developed descriptor sets for predictive modeling of Langmuir isotherms for proteins at different pH values between pH 5 and 10 and varying ionic strength in the range of 10-100mM. The resulting model has a high correlation of calculated descriptors and experimental results, with a coefficient of determination of 0.82 and a predictive coefficient of determination of 0.92 for unknown molecular structures and conditions. The agreement of calculated molecular interaction orientations with both, experimental results as well as molecular dynamic simulations from literature is shown. The developed descriptors provide the means for improved QSAR models of chromatographic processes, as they reflect the complex interactions of biomolecules with chromatographic phases. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Interaction of cholesterol-conjugated ionizable amino lipids with biomembranes: lipid polymorphism, structure-activity relationship, and implications for siRNA delivery.

    Science.gov (United States)

    Zhang, Jingtao; Fan, Haihong; Levorse, Dorothy A; Crocker, Louis S

    2011-08-02

    Delivery of siRNA is a major obstacle to the advancement of RNAi as a novel therapeutic modality. Lipid nanoparticles (LNP) consisting of ionizable amino lipids are being developed as an important delivery platform for siRNAs, and significant efforts are being made to understand the structure-activity relationship (SAR) of the lipids. This article uses a combination of small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) to evaluate the interaction between cholesterol-conjugated ionizable amino lipids and biomembranes, focusing on an important area of lipid SAR--the ability of lipids to destabilize membrane bilayer structures and facilitate endosomal escape. In this study, cholesterol-conjugated amino lipids were found to be effective in increasing the order of biomembranes and also highly effective in inducing phase changes in biological membranes in vitro (i.e., the lamellar to inverted hexagonal phase transition). The phase transition temperatures, determined using SAXS and DSC, serve as an indicator for ranking the potency of lipids to destabilize endosomal membranes. It was found that the bilayer disruption ability of amino lipids depends strongly on the amino lipid concentration in membranes. Amino lipids with systematic variations in headgroups, the extent of ionization, tail length, the degree of unsaturation, and tail asymmetry were evaluated for their bilayer disruption ability to establish SAR. Overall, it was found that the impact of these lipid structure changes on their bilayer disruption ability agrees well with the results from a conceptual molecular "shape" analysis. Implications of the findings from this study for siRNA delivery are discussed. The methods reported here can be used to support the SAR screening of cationic lipids for siRNA delivery, and the information revealed through the study of the interaction between cationic lipids and biomembranes will contribute significantly to the design of more efficient si

  9. Molecular Docking, Molecular Dynamics, and Structure-Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists.

    Science.gov (United States)

    Noha, Stefan M; Schmidhammer, Helmut; Spetea, Mariana

    2017-06-21

    Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure-activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3-7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design.

  10. Support vector regression-guided unravelling: antioxidant capacity and quantitative structure-activity relationship predict reduction and promotion effects of flavonoids on acrylamide formation

    Science.gov (United States)

    Huang, Mengmeng; Wei, Yan; Wang, Jun; Zhang, Yu

    2016-09-01

    We used the support vector regression (SVR) approach to predict and unravel reduction/promotion effect of characteristic flavonoids on the acrylamide formation under a low-moisture Maillard reaction system. Results demonstrated the reduction/promotion effects by flavonoids at addition levels of 1-10000 μmol/L. The maximal inhibition rates (51.7%, 68.8% and 26.1%) and promote rates (57.7%, 178.8% and 27.5%) caused by flavones, flavonols and isoflavones were observed at addition levels of 100 μmol/L and 10000 μmol/L, respectively. The reduction/promotion effects were closely related to the change of trolox equivalent antioxidant capacity (ΔTEAC) and well predicted by triple ΔTEAC measurements via SVR models (R: 0.633-0.900). Flavonols exhibit stronger effects on the acrylamide formation than flavones and isoflavones as well as their O-glycosides derivatives, which may be attributed to the number and position of phenolic and 3-enolic hydroxyls. The reduction/promotion effects were well predicted by using optimized quantitative structure-activity relationship (QSAR) descriptors and SVR models (R: 0.926-0.994). Compared to artificial neural network and multi-linear regression models, SVR models exhibited better fitting performance for both TEAC-dependent and QSAR descriptor-dependent predicting work. These observations demonstrated that the SVR models are competent for predicting our understanding on the future use of natural antioxidants for decreasing the acrylamide formation.

  11. Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

    Science.gov (United States)

    Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

    2018-03-28

    In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (casein presents an excellent source to produce ACE inhibitory peptides.

  12. Comparative pharmacodynamic analysis of imidazoline compounds using rat model of ocular mydriasis with a test of quantitative structure-activity relationships.

    Science.gov (United States)

    Raczak-Gutknecht, Joanna; Nasal, Antoni; Frąckowiak, Teresa; Kornicka, Anita; Sączewski, Franciszek; Wawrzyniak, Renata; Kubik, Łukasz; Kaliszan, Roman

    2017-09-10

    Imidazol(in)e derivatives, having the chemical structure similar to clonidine, exert diverse pharmacological activities connected with their interactions with alpha2-adrenergic receptors, e.g. hypotension, bradycardia, sedation as well as antinociceptive, anxiolytic, antiarrhythmic, muscle relaxant and mydriatic effects. The mechanism of pupillary dilation observed after systemic administration of imidazol(in)es to rats, mice and cats depends on the stimulation of postsynaptic alpha2-adrenoceptors within the brain. It was proved that the central nervous system (CNS)-localized I1-imidazoline receptors are not engaged in those effects. It appeared interesting to analyze the CNS-mediated pharmacodynamics of imidazole(in)e agents in terms of their chromatographic and calculation chemistry-derived parameters. In the present study a systematic determination and comparative pharmacometric analysis of mydriatic effects in rats were performed on a series of 20 imidazol(in)e agents, composed of the well-known drugs and of the substances used in experimental pharmacology. The eye pupil dilatory activities of the compounds were assessed in anesthetized Wistar rats according to the established Koss method. Among twenty imidazol(in)e derivatives studied, 18 produced diverse dose-dependent mydriatic effects. In the quantitative structure-activity relationships (QSAR) analysis, the pharmacological data (half maximum mydriatic effect - ED 50 in μmol/kg) were considered along with the structural parameters of the agents from molecular modeling. The theoretically calculated lipophilicity parameters, CLOGP, of imidazol(in)es, as well as their lipophilicity parameters from HPLC, logk w , were also considered. The attempts to derive statistically significant QSAR equations for a full series of the agents under study were unsuccessful. However, for a subgroup of eight apparently structurally related imidazol(in)es a significant relationship between log(1/ED 50 ) and logk w values was

  13. Inhibition of 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure-Activity Relationship in a Model System.

    Science.gov (United States)

    Yu, Chundi; Shao, Zeping; Liu, Bing; Zhang, Yan; Wang, Shuo

    2016-08-01

    The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure-activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect. © 2016 Institute of Food Technologists®

  14. Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.

    Directory of Open Access Journals (Sweden)

    Megan Leander

    Full Text Available Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS, a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (RhpMS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3-6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3-6 lock

  15. Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents.

    Science.gov (United States)

    Aratikatla, Eswar K; Valkute, Tushar R; Puri, Sunil K; Srivastava, Kumkum; Bhattacharya, Asish K

    2017-09-29

    Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC 50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3-57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC 50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC 50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC 50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1

  16. Understanding of the structure activity relationship of PtPd bimetallic catalysts prepared by surface organometallic chemistry and ion exchange during the reaction of iso-butane with hydrogen

    KAUST Repository

    Al-Shareef, Reem A.; Harb, Moussab; Saih, Youssef; Ould-Chikh, Samy; Roldan, Manuel A.; Anjum, Dalaver H.; Guyonnet, Elodie Bile; Candy, Jean-Pierre; Jan, Deng-Yang; Abdo, Suheil F.; Aguilar-Tapia, Antonio; Proux, Olivier; Hazemann, Jean-Louis; Basset, Jean-Marie

    2018-01-01

    Well-defined silica supported bimetallic catalysts Pt100-x Pdx were prepared by Surface Organometallic Chemistry (SOMC) and Ionic-Exchange (IE) methods. For all investigated catalysts, iso-butane reaction with hydrogen under differential conditions led to the formation of methane and propane, n-butane, and traces of iso-butylene. The total reaction rate decreased with increasing the Pd loading for both catalysts series as a result of decreasing turnover rate of both isomerization and hydrogenolysis. In the case of Pt100-x Pdx(SOMC) catalysts, the experimental results in combination with DFT calculations suggested a selective coverage of Pt (1 0 0) surface by agglomerated Pd atoms like “islands”, assuming that each metal roughly keeps its intrinsic catalytic properties with relatively small electron transfer from Pt to Pd in the case of Pt-rich sample and from Pd to Pt in the case of Pd-rich sample. For the PtPd catalysts prepared by IE, the catalytic behavior could be explained by the formation of a surface alloy between Pt and Pd in the case of Pd-rich sample and by the segregation of a small amount of Pd on the surface in the case of Pt-rich sample, as demonstrated by TEM, EXAFS and DFT. The catalytic results were explained by a structure activity relationship based on the proposed mechanism of CH bond and CC bond activation and cleavage for iso-butane hydrogenolysis, isomerization, cracking and dehydrogenation.

  17. Understanding of the structure activity relationship of PtPd bimetallic catalysts prepared by surface organometallic chemistry and ion exchange during the reaction of iso-butane with hydrogen

    KAUST Repository

    Alshareef, Reem Abdul aziz Hamed

    2018-04-25

    Well-defined silica supported bimetallic catalysts Pt100-x Pdx were prepared by Surface Organometallic Chemistry (SOMC) and Ionic-Exchange (IE) methods. For all investigated catalysts, iso-butane reaction with hydrogen under differential conditions led to the formation of methane and propane, n-butane, and traces of iso-butylene. The total reaction rate decreased with increasing the Pd loading for both catalysts series as a result of decreasing turnover rate of both isomerization and hydrogenolysis. In the case of Pt100-x Pdx(SOMC) catalysts, the experimental results in combination with DFT calculations suggested a selective coverage of Pt (1 0 0) surface by agglomerated Pd atoms like “islands”, assuming that each metal roughly keeps its intrinsic catalytic properties with relatively small electron transfer from Pt to Pd in the case of Pt-rich sample and from Pd to Pt in the case of Pd-rich sample. For the PtPd catalysts prepared by IE, the catalytic behavior could be explained by the formation of a surface alloy between Pt and Pd in the case of Pd-rich sample and by the segregation of a small amount of Pd on the surface in the case of Pt-rich sample, as demonstrated by TEM, EXAFS and DFT. The catalytic results were explained by a structure activity relationship based on the proposed mechanism of CH bond and CC bond activation and cleavage for iso-butane hydrogenolysis, isomerization, cracking and dehydrogenation.

  18. Modeling Chemical Interaction Profiles: I. Spectral Data-Activity Relationship and Structure-Activity Relationship Models for Inhibitors and Non-inhibitors of Cytochrome P450 CYP3A4 and CYP2D6 Isozymes

    Directory of Open Access Journals (Sweden)

    Richard D. Beger

    2012-03-01

    Full Text Available An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals—drugs, pesticides, and environmental pollutants—interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP enzymes. In the present work, spectral data-activity relationship (SDAR and structure-activity relationship (SAR approaches were used to develop machine-learning classifiers of inhibitors and non-inhibitors of the CYP3A4 and CYP2D6 isozymes. The models were built upon 602 reference pharmaceutical compounds whose interactions have been deduced from clinical data, and 100 additional chemicals that were used to evaluate model performance in an external validation (EV test. SDAR is an innovative modeling approach that relies on discriminant analysis applied to binned nuclear magnetic resonance (NMR spectral descriptors. In the present work, both 1D 13C and 1D 15N-NMR spectra were used together in a novel implementation of the SDAR technique. It was found that increasing the binning size of 1D 13C-NMR and 15N-NMR spectra caused an increase in the tenfold cross-validation (CV performance in terms of both the rate of correct classification and sensitivity. The results of SDAR modeling were verified using SAR. For SAR modeling, a decision forest approach involving from 6 to 17 Mold2 descriptors in a tree was used. Average rates of correct classification of SDAR and SAR models in a hundred CV tests were 60% and 61% for CYP3A4, and 62% and 70% for CYP2D6, respectively. The rates of correct classification of SDAR and SAR models in the EV test were 73% and 86% for CYP3A4, and 76% and 90% for CYP2D6, respectively. Thus, both SDAR and SAR methods demonstrated a comparable performance in modeling a large set of structurally diverse data. Based on unique NMR structural descriptors, the new SDAR modeling method complements the existing SAR

  19. Investigation of landscape and lake acidification relationships

    Energy Technology Data Exchange (ETDEWEB)

    Rush, R.M.; Honea, R.B.; Krug, E.C.; Peplies, R.W.; Dobson, J.E.; Baxter, F.P.

    1985-10-01

    This interim report presents the rationale and initial results for a program designed to gather and analyze information essential to a better understanding of lake acidification in the northeastern United States. The literature pertinent to a study of landscape and lake acidification relationships is reviewed and presented as the rationale for a landscape/lake acidification study. The results of a study of Emmons Pond in northwestern Connecticut are described and lead to the conclusion that a landscape change was a contributor to the acidification of this pond. A regional study of sixteen lakes in southern New England using Landsat imagery is described, and preliminary observations from a similar study in the Adirondack Mountains are given. These results indicate that satellite imagery can be useful in identifying types of ground cover important to landscape/lake acidification relationships.

  20. Investigation of possible sun-weather relationships

    International Nuclear Information System (INIS)

    Businger, S.

    1978-01-01

    Statistical correlations between anomalous solar activity (as denoted by large solar flares, active plages, and interplanetary magnetic sector boundaries) and the circulation of the troposphere are reviewed. Two indices (measuring atmospheric vorticity and mean zonal geostrophic flow in the northern hemisphere) are analyzed in an effort to reveal possible sun-weather relationships. The result of this analysis provides no additional statistical evidence for a connection between solar activity and the weather. Finally, physical mechanisms that have been suggested to explain the claimed correlations are discussed

  1. Identification of new 2,5-diketopiperazine derivatives as simultaneous effective inhibitors of αβ-tubulin and BCRP proteins: Molecular docking, Structure-Activity Relationships and virtual consensus docking studies

    Science.gov (United States)

    Fani, Najmeh; Sattarinezhad, Elham; Bordbar, Abdol-Khalegh

    2017-06-01

    In the first part of this paper, docking method was employed in order to study the binding mechanism of breast cancer resistance protein (BCRP) with a group of previously synthesized TPS-A derivatives which known as potent inhibitors of this protein to get insight into drug binding site of BCRP and to explore structure-activity relationship of these compounds. Molecular docking results showed that most of these compounds bind in the binding site of BCRP at the interface between the membrane and outer environment. In the second part, a group of designed TPS-A derivatives which showed good binding energies in the binding site of αβ-tubulin in the previous study were chosen to study their binding energies in the binding site of BCRP to investigate their simultaneous inhibitory effect on both αβ-tubulin and BCRP. The results showed that all of these compounds bind to the binding site of BCRP with relatively suitable binding energies and therefore could be potential inhibitors of both αβ-tubulin and BCRP proteins. Finally, virtual consensus docking method was utilized with the aim of design of new 2,5-diketopiperazine derivatives with significant inhibitory effect on both αβ-tubulin and BCRP proteins. For this purpose binding energies of a library of 2,5-diketopiperazine derivatives in the binding sites of αβ-tubulin and BCRP was investigated by using AutoDock and AutoDock vina tools. Molecular docking results revealed that a group of 36 compounds among them exhibit strong anti-tubulin and anti-BCRP activity.

  2. Advising as Servant Leadership: Investigating the Relationship

    Science.gov (United States)

    Paul, W. Kohle; Smith, K. Courtney; Dochney, Brendan J.

    2012-01-01

    Advisors serve in many, often overlooked, roles. We investigated the supposition that McClellan (2007a) espoused between academic advising and servant leadership. Our hypotheses, that measures of servant leadership and developmental advising are correlated and that wisdom is the best predictor of developmental advising behaviors, were supported.…

  3. Best of friends? Investigating the dog-human relationship

    OpenAIRE

    Rehn, Therese

    2013-01-01

    Dogs are commonly referred to as man's best friend, but the main focus of this thesis was to investigate how the dog experiences the relationship. The first part of the thesis dealt with methodology currently used to assess the dog-human relationship: the Strange Situation Procedure (SSP) and the Monash Dog Owner Relationship Scale (MDORS). In one experiment, possible associations between the dog's bond to its owner (using the SSP) and the strength of the owner's relationship to the dog (...

  4. Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region.

    Directory of Open Access Journals (Sweden)

    Victoria S Paulsen

    Full Text Available Arasin 1 is a 37 amino acid long proline-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. In this work the active region of arasin 1 was identified through structure-activity studies using different peptide fragments derived from the arasin 1 sequence. The pharmacophore was found to be located in the proline/arginine-rich NH(2 terminus of the peptide and the fragment arasin 1(1-23 was almost equally active to the full length peptide. Arasin 1 and its active fragment arasin 1(1-23 were shown to be non-toxic to human red blood cells and arasin 1(1-23 was able to bind chitin, a component of fungal cell walls and the crustacean shell. The mode of action of the fully active N-terminal arasin 1(1-23 was explored through killing kinetic and membrane permeabilization studies. At the minimal inhibitory concentration (MIC, arasin 1(1-23 was not bactericidal and had no membrane disruptive effect. In contrast, at concentrations of 5×MIC and above it was bactericidal and interfered with membrane integrity. We conclude that arasin 1(1-23 has a different mode of action than lytic peptides, like cecropin P1. Thus, we suggest a dual mode of action for arasin 1(1-23 involving membrane disruption at peptide concentrations above MIC, and an alternative mechanism of action, possibly involving intracellular targets, at MIC.

  5. Anti-leishmanial and structure-activity relationship of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives

    Directory of Open Access Journals (Sweden)

    Asunción Burguete

    2008-12-01

    Full Text Available A series of ring substituted 3-phenyl-1-(1,4-di-N-oxide quinoxalin-2-yl-2-propen-1-one derivatives were synthesized and tested for in vitro leishmanicidal activity against amastigotes of Leishmania amazonensis in axenical cultures and murine infected macrophages. Structure-activity relationships demonstrated the importance of a radical methoxy at position R3', R4' and R5'. (2E-3-(3,4,5-trimethoxy-phenyl-1-(3,6,7-trimethyl-1,4-dioxy-quinoxalin-2-yl-propenone was the most active. Cytotoxicity on macrophages revealed that this product was almost six times more active than toxic.

  6. Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.

    Science.gov (United States)

    Pang, Siu-Kwong

    2017-03-30

    Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Imidazole derivatives as angiotensin II AT1 receptor blockers: Benchmarks, drug-like calculations and quantitative structure-activity relationships modeling

    Science.gov (United States)

    Alloui, Mebarka; Belaidi, Salah; Othmani, Hasna; Jaidane, Nejm-Eddine; Hochlaf, Majdi

    2018-03-01

    We performed benchmark studies on the molecular geometry, electron properties and vibrational analysis of imidazole using semi-empirical, density functional theory and post Hartree-Fock methods. These studies validated the use of AM1 for the treatment of larger systems. Then, we treated the structural, physical and chemical relationships for a series of imidazole derivatives acting as angiotensin II AT1 receptor blockers using AM1. QSAR studies were done for these imidazole derivatives using a combination of various physicochemical descriptors. A multiple linear regression procedure was used to design the relationships between molecular descriptor and the activity of imidazole derivatives. Results validate the derived QSAR model.

  8. Structure-Activity Relationships Based on 3D-QSAR CoMFA/CoMSIA and Design of Aryloxypropanol-Amine Agonists with Selectivity for the Human β3-Adrenergic Receptor and Anti-Obesity and Anti-Diabetic Profiles

    Directory of Open Access Journals (Sweden)

    Marcos Lorca

    2018-05-01

    Full Text Available The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB, and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR techniques. This is the first combined comparative molecular field analysis (CoMFA and comparative molecular similarity index analysis (CoMSIA study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r2ncv = 0.993 and 0.984 and values of r2test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation (q2, r2, r2m, etc. and a final series of compounds was designed and their biological activity was predicted (best pEC50 = 8.561.

  9. Centrally acting serotonergic and dopaminergic agents. 1. Synthesis and structure-activity relationships of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives.

    Science.gov (United States)

    Lin, C H; Haadsma-Svensson, S R; Lahti, R A; McCall, R B; Piercey, M F; Schreur, P J; Von Voigtlander, P F; Smith, M W; Chidester, C G

    1993-04-16

    The synthesis and structure-activity relationships (SAR) of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives (3) are described. These compounds are conformationally restricted, angular tricyclic analogs of 2-aminotetralin. The synthesis was achieved in several steps from the corresponding 2-tetralones. The enantiomers of the cis analogs were obtained from either fractional recrystallizations of the diastereomeric salts of di-p-toluoyl-L-(or D)-tartaric acid or an asymmetric synthesis using chiral (R)-alpha-methylbenzylamine. All analogs were evaluated in the in vitro 5-HT1A and D2 binding assays and selected analogs were investigated further in biochemical and behavioral tests. Analogs with 9-methoxy substitution (R1 in 3) showed mixed 5-HT1A agonist and dopamine antagonist activities whereas the corresponding 9-hydroxy analogs displayed selective 5-HT1A agonist activity. The cis analogs were found to be more potent than the corresponding trans analogs and in the cis series, the (3aR)-(-)-enantiomers displayed higher potency. Nitrogen substitution (R2 in 3) with either an n-propyl or an allyl group produced similar activities whereas replacement with a bulky alpha-methylbenzyl group resulted in loss of activity. Analogs without aromatic substitution (R1 = H in 3) still showed good 5-HT1A agonist activity, although less potent than the 9-methoxy series. In this case, the trans analogs possessed equal or higher in vitro 5-HT1A affinity than the corresponding cis analogs. Analogs with either 6-methoxy or 6-hydroxy substitution (R1 in 3) were found to display dopamine antagonist properties. However, only N-allyl analogs showed this activity. In the 6-methoxy-N-allyl series, the cis analog was found to be more potent than the trans analog. Again, between the pair of cis enantiomers, the (3aR)-(-)-enantiomer showed higher potency. Incorporation of an additional methyl group into 9-methoxy cis analogs at C-2 resulted in retention of potent 5-HT1A agonist activity.

  10. 2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Xin-Juan Yang

    2013-08-01

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

  11. MS/MS fragmentation-guided search of TMG-chitooligomycins and their structure-activity relationship in specific β-N-acetylglucosaminidase inhibition.

    Science.gov (United States)

    Usuki, Hirokazu; Yamamoto, Yukihiro; Kumagai, Yuya; Nitoda, Teruhiko; Kanzaki, Hiroshi; Hatanaka, Tadashi

    2011-04-21

    The reducing tetrasaccharide TMG-chitotriomycin (1) is an inhibitor of β-N-acetylglucosaminidase (GlcNAcase), produced by the actinomycete Streptomyces anulatus NBRC13369. The inhibitor shows a unique inhibitory spectrum, that is, selectivity toward enzymes from chitin-containing organisms such as insects and fungi. Nevertheless, its structure-selectivity relationship remains to be clarified. In this study, we conducted a structure-guided search of analogues of 1 in order to obtain diverse N,N,N-trimethylglucosaminium (TMG)-containing chitooligosaccharides. In this approach, the specific fragmentation profile of 1 on ESI-MS/MS analysis was used for the selective detection of desired compounds. As a result, two new analogues, named TMG-chitomonomycin (3) and TMG-chitobiomycin (2), were obtained from a culture filtrate of 1-producing Streptomyces. Their enzyme-inhibiting activity revealed that the potency and selectivity depended on the degree of polymerization of the reducing end GlcNAc units. Furthermore, a computational modeling study inspired the inhibitory mechanism of TMG-related compounds as a mimic of the substrate in the Michaelis complex of the GH20 enzyme. This study is an example of the successful application of a MS/MS experiment for structure-guided isolation of natural products.

  12. Distributing Correlation Coefficients of Linear Structure-Activity/Property Models

    Directory of Open Access Journals (Sweden)

    Sorana D. BOLBOACA

    2011-12-01

    Full Text Available Quantitative structure-activity/property relationships are mathematical relationships linking chemical structure and activity/property in a quantitative manner. These in silico approaches are frequently used to reduce animal testing and risk-assessment, as well as to increase time- and cost-effectiveness in characterization and identification of active compounds. The aim of our study was to investigate the pattern of correlation coefficients distribution associated to simple linear relationships linking the compounds structure with their activities. A set of the most common ordnance compounds found at naval facilities with a limited data set with a range of toxicities on aquatic ecosystem and a set of seven properties was studied. Statistically significant models were selected and investigated. The probability density function of the correlation coefficients was investigated using a series of possible continuous distribution laws. Almost 48% of the correlation coefficients proved fit Beta distribution, 40% fit Generalized Pareto distribution, and 12% fit Pert distribution.

  13. Investigation of the relationship between ground and engineering ...

    Indian Academy of Sciences (India)

    In order to investigate possible ground motion amplification in earthquake resistant building design, relationship between the ground and engineering bedrock must be ensured. In order to provide this relation, structure, basic characteristics, and thickness of the ground are investigated. In this context, calculating ground ...

  14. 1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies.

    Science.gov (United States)

    La Regina, Giuseppe; D'Auria, Felicia Diodata; Tafi, Andrea; Piscitelli, Francesco; Olla, Stefania; Caporuscio, Fabiana; Nencioni, Lucia; Cirilli, Roberto; La Torre, Francesco; De Melo, Nadja Rodrigues; Kelly, Steven L; Lamb, David C; Artico, Marino; Botta, Maurizio; Palamara, Anna Teresa; Silvestri, Romano

    2008-07-10

    New 1-[(3-aryloxy-3-aryl)propyl]-1 H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure-activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketoconazole, miconazole, and econazole, and were more potent than fluconazole. Several derivatives ( 10, 12, 14, 18- 20, 24, 28, 29, 30, and 34) turned out to be potent inhibitors of C. albicans strains resistant to fluconazole, with MIC values less than 10 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC

  15. Comparison of 3D quantitative structure-activity relationship methods: Analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis

    Science.gov (United States)

    Woolfrey, John R.; Avery, Mitchell A.; Doweyko, Arthur M.

    1998-03-01

    Two three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL), were compared with respect to the analysis of a training set of 154 artemisinin analogues. Five models were created, including a complete HASL and two trimmed versions, as well as two CoMFA models (leave-one-out standard CoMFA and the guided-region selection protocol). Similar r2 and q2 values were obtained by each method, although some striking differences existed between CoMFA contour maps and the HASL output. Each of the four predictive models exhibited a similar ability to predict the activity of a test set of 23 artemisinin analogues, although some differences were noted as to which compounds were described well by either model.

  16. Insights into the structure-activity relationship of the anticancer compound ZJ-101, a derivative of marine natural product superstolide A: A critical role played by the conjugated trienyl lactone moiety.

    Science.gov (United States)

    Qian, Shan; Shah, Aashay K; Head, Sarah A; Liu, Jun O; Jin, Zhendong

    2016-08-01

    Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure-activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2-C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4-C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Structure-activity relationship of linear tetrapeptides Tic-DPhe-Arg-Trp-NH2 at the human melanocortin-4 receptor and effects on feeding behaviors in rat.

    Science.gov (United States)

    Ye, Zhixiong; MacNeil, Tanya; Weinberg, David H; Kalyani, Rubana N; Tang, Rui; Strack, Alison M; Murphy, Beth A; Mosley, Ralph T; Euan MacIntyre, D; Van der Ploeg, Lex H T; Patchett, Arthur A; Wyvratt, Matthew J; Nargund, Ravi P

    2005-10-01

    The melanocortin subtype-4 receptor (MC4R) has been implicated in the control of feeding behavior and body weight regulation. A series of tetrapeptides, based on Tic-DPhe-Arg-Trp-NH2-a mimic of the putative message sequence "His-Phe-Arg-Trp" and modified at the DPhe position, were prepared and pharmacologically characterized for potency and selectivity. Substitution of His with Tic gave peptides with significant increases in selectivity. The effects of the substitution pattern of DPhe were investigated and it has significant influences on potency and the level of the maximum cAMP accumulation. Intracerebroventricular administration of peptide 10 induced significant inhibition of cumulative overnight food intake and feeding duration in rats.

  18. In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling.

    Science.gov (United States)

    Becker, John V W; van der Merwe, Marina M; van Brummelen, Anna C; Pillay, Pamisha; Crampton, Bridget G; Mmutlane, Edwin M; Parkinson, Chris; van Heerden, Fanie R; Crouch, Neil R; Smith, Peter J; Mancama, Dalu T; Maharaj, Vinesh J

    2011-10-11

    Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis. The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that

  19. In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae: identification of its main active constituent, structure-activity relationship studies and gene expression profiling

    Directory of Open Access Journals (Sweden)

    van Heerden Fanie R

    2011-10-01

    Full Text Available Abstract Background Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile. Methods Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls, followed by oligonucleotide microarray- and data analysis. Results The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10 of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action

  20. Antibacterial and Antioxidant Activity of Essential Oil Terpenes against Pathogenic and Spoilage-Forming Bacteria and Cell Structure-Activity Relationships Evaluated by SEM Microscopy

    Directory of Open Access Journals (Sweden)

    Hatice Zengin

    2014-11-01

    Full Text Available The antibacterial activity and antioxidant effect of the compounds α-terpineol, linalool, eucalyptol and α-pinene obtained from essential oils (EOs, against pathogenic and spoilage forming bacteria were determined. The antibacterial activities of these compounds were observed in vitro on four Gram-negative and three Gram-positive strains. S. putrefaciens was the most resistant bacteria to all tested components, with MIC values of 2% or higher, whereas E. coli O157:H7 was the most sensitive strain among the tested bacteria. Eucalyptol extended the lag phase of S. Typhimurium, E. coli O157:H7 and S. aureus at the concentrations of 0.7%, 0.6% and 1%, respectively. In vitro cell growth experiments showed the tested compounds had toxic effects on all bacterial species with different level of potency. Synergistic and additive effects were observed at least one dose pair of combination against S. Typhimurium, E. coli O157:H7 and S. aureus, however antagonistic effects were not found in these combinations. The results of this first study are encouraging for further investigations on mechanisms of antimicrobial activity of these EO components.

  1. Structure-activity relationship in the passage of different pyrrolizidine alkaloids through the gastrointestinal barrier: ABCB1 excretes heliotrine and echimidine.

    Science.gov (United States)

    Hessel, Stefanie; Gottschalk, Christoph; Schumann, Dania; These, Anja; Preiss-Weigert, Angelika; Lampen, Alfonso

    2014-05-01

    1,2-Unsaturated pyrrolizidine alkaloids (PA) are found in plants such as Asteraceae and Boraginaceae families. Acute PA poisoning via contaminated food or feed causes severe damage to liver depending on species-specific oral bioavailability. For assessing PA bioavailability, their passage across the intestinal barrier was investigated using Caco-2 cells. Differentiated Caco-2 cells were exposed in transport chambers to the PA heliotrine (Hn), echimidine (Em), senecionine (Sc), and senkirkine (Sk). Cell supernatants were analyzed by LC-MS/MS. PA pass Caco-2 monolayer from the apical into basolateral compartment depending on their chemical structure. Compared to the cyclic diesters Sc and Sk with a passage rate of 47% ± 4 and 40% ± 3, respectively, the transferred amount of the monoester Hn (32% ± 3) and open-chained diester Em (13% ± 2) was substantially lower. This suggested an active transport of Hn and Em. Using Madin-Darby canine kidney II/P-glycoprotein (ABCB1)-overexpressing cells, the active excretion of Hn and Em by ABCB1 from the gastrointestinal epithelium into the gut lumen was shown. PA cross the intestinal barrier structure-dependently. The passage of the noncyclic PA Hn and Em is reduced by an ABCB1-driven efflux into the gastrointestinal lumen resulting in a decreased oral bioavailability. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Design and optimization of N-acylhydrazone pyrimidine derivatives as E. coli PDHc E1 inhibitors: Structure-activity relationship analysis, biological evaluation and molecular docking study.

    Science.gov (United States)

    He, Haifeng; Xia, Hongying; Xia, Qin; Ren, Yanliang; He, Hongwu

    2017-10-15

    By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel 'open-chain' classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1-23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC 50 =0.15-23.55μM). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC 50 values of 0.60, 0.15, 0.39 and 0.34μM against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E.coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL-60 Human Leukemia Cells: Nuclear Localization and Structure-Activity Relationships.

    Science.gov (United States)

    Okubo, Shinya; Uto, Takuhiro; Goto, Aya; Tanaka, Hiroyuki; Nishioku, Tsuyoshi; Yamada, Katsushi; Shoyama, Yukihiro

    2017-01-01

    Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.

  4. The exceptional ethics of the investigator-subject relationship.

    Science.gov (United States)

    Sachs, Benjamin

    2010-02-01

    This article concerns the validity of six canonical rules that institutional review boards use to constrain the behavior of investigators. These rules require investigators to design their studies in a scientifically valid way, not pay their subjects to take risks, minimize risks to their subjects, secure for their subjects access to effective interventions post-trial, not pay their subjects too much and allow their subjects to withdraw from the study unconditionally. Enforcement of these rules is problematic because there are other relationships that seem to be like the investigator-subject relationship in all ethically relevant respects, such as the employer-employee and volunteer organizer-volunteer relationships, to which we would not dream of applying these same rules. Applying these rules in one context but not the others is a violation of ethical consistency I label "exceptionalism." We should conclude that it is time to reexamine the validity of the six rules.

  5. Structure Activity Relationship of Brevenal Hydrazide Derivatives

    Directory of Open Access Journals (Sweden)

    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.

  6. Investigating the Relationship between Organizational Dissent and Life Satisfaction

    Science.gov (United States)

    Dagli, Abidin

    2017-01-01

    The aim of this study is to investigate the relationship between organizational dissent and life satisfaction perceptions of public primary school teachers. This research is a descriptive study in relational survey model. The sample consists of randomly chosen 200 primary school teachers who are working in Diyarbakir city center during the…

  7. An investigation of the relationship between innovation and cultural diversity.

    Science.gov (United States)

    Kandler, Anne; Laland, Kevin N

    2009-08-01

    In this paper we apply reaction-diffusion models to explore the relationship between the rate of behavioural innovation and the level of cultural diversity. We investigate how both independent invention and the modification and refinement of established innovations impact on cultural dynamics and diversity. Further, we analyse these relationships in the presence of biases in cultural learning and find that the introduction of new variants typically increases cultural diversity substantially in the short term, but may decrease long-term diversity. Independent invention generally supports higher levels of cultural diversity than refinement. Repeated patterns of innovation through refinement generate characteristic oscillating trends in diversity, with increasing trends towards greater average diversity observed for medium but not low innovation rates. Conformity weakens the relationship between innovation and diversity. The level of cultural diversity, and pattern of temporal dynamics, potentially provide clues as to the underlying process, which can be used to interpret empirical data.

  8. An Evolution in Research Practice for Investigating International Business Relationships

    OpenAIRE

    Anne HAMPTON; James ROWELL

    2013-01-01

    The purpose of this paper is to discuss the development and rationale of research methodology for a specific topic of research. The topic in question is an investigation into international business relationships, a complex subject and one that is very topical in the growing world of international business. It is intended to examine the logical development of research practice in our study and to show the changing thought processes and justifications we have made over a period of time. It is h...

  9. Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.

    Science.gov (United States)

    Shrestha, Aarajana; Jin Oh, Hye; Kim, Mi Jin; Pun, Nirmala Tilija; Magar, Til Bahadur Thapa; Bist, Ganesh; Choi, Hongseok; Park, Pil-Hoon; Lee, Eung-Seok

    2017-06-16

    As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Kinetic Study of the Aroxyl-Radical-Scavenging Activity of Five Fatty Acid Esters and Six Carotenoids in Toluene Solution: Structure-Activity Relationship for the Hydrogen Abstraction Reaction.

    Science.gov (United States)

    Mukai, Kazuo; Yoshimoto, Maya; Ishikura, Masaharu; Nagaoka, Shin-Ichi

    2017-08-17

    A kinetic study of the reaction between an aroxyl radical (ArO • ) and fatty acid esters (LHs 1-5, ethyl stearate 1, ethyl oleate 2, ethyl linoleate 3, ethyl linolenate 4, and ethyl arachidonate 5) has been undertaken. The second-order rate constants (k s ) for the reaction of ArO • with LHs 1-5 in toluene at 25.0 °C have been determined spectrophotometrically. The k s values obtained increased in the order of LH 1 LHs 1-5. The k s value for LH 5 was 2.93 × 10 -3 M -1 s -1 . From the result, it has been clarified that the reaction of ArO • with LHs 1-5 was explained by an allylic hydrogen abstraction reaction. A similar kinetic study was performed for the reaction of ArO • with six carotenoids (Car-Hs 1-6, astaxanthin 1, β-carotene 2, lycopene 3, capsanthin 4, zeaxanthin 5, and lutein 6). The k s values obtained increased in the order of Car-H 1 LHs 1-5. The results of detailed analyses of the k s values for the above reaction indicated that the reaction was also explained by an allylic hydrogen abstraction reaction. Furthermore, the structure-activity relationship for the reaction was discussed by taking the result of density functional theory calculation reported by Martinez and Barbosa into account.

  11. Influence of lipophilicity in O-acyl and O-alkyl derivatives of juglone and lawsone: a structure-activity relationship study in the search for natural herbicide models.

    Science.gov (United States)

    Durán, Alexandra G; Chinchilla, Nuria; Molinillo, José Mg; Macías, Francisco A

    2018-03-01

    Naphthoquinones are known for their broad range of biological activities. Given the increasing demands of consumers in relation to food quality and growing concerns about the impact of synthetic herbicides, it is necessary to search for new agrochemicals. Natural products and allelopathy provide new alternatives for the development of pesticides with lower toxicity and greater environmental compatibility. A structure-activity relationship to evaluate the effect of bioavailability was performed. A total of 44 O-acyl and O-alkyl derivatives of juglone and lawsone with different linear chain lengths were prepared. These compounds were tested on etiolated wheat coleoptiles, standard target species (STS) and four weeds, Echinochloa crus-galli L., Lolium rigidum Gaud., Lolium perenne L. and Avena fatua L. The results showed a strong influence of lipophilicity and, in most cases, the data fitted a logP-dependent quadratic mathematical model. The effects produced were mostly stunting and necrosis caused by growth inhibition. The potential structure and activity behaviour is described. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Investigation of relationship between sediment yield and landslide in Iran

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    Samad Shadfar

    2012-07-01

    Full Text Available Landslides have been made irreversible damage to urban areas and economic in Iran. In this research, at first, for Investigation of relationship between landslide and sediment yield was recognized some of effective factors on Landslide. These Factors were processed with use of ILWIS and Arc GIS software’s. Landslide hazard zonation was done using Density Area and Index Overlay methods in GIS and evaluated them using Quality Sum index. In after phase, were determined sediment yield in each of them. Finally, occurrence rate landslide investigated in sediment yield zones. The results indicated that, slope, lithology and distance from the hydrographic network have the greatest impact on landslides. Most of the landslides have occurred in the 15-40% slope class, units of conglomerate and marl, and within one km of drainage network. On the other hand, the relationship between landslide frequency and distance of the fault was not a linear relationship and Almost 60 %of landslides have occurred distance of one km of the faults. Evaluation using Quality Sum index showed that the density Area has a more logical answer and as Appropriate method will be introduced in the basin. Investigation of deposition potential in sub-basins showed that Javaherdeh sub basin with 92.74 deposition potential is the first priority. Nedasht and latmohalleh sub basins, each with a deposition potential of 20.08 are the next priorities. Relationship between landslide area and deposition potential were identified as 8/91% of the landslides in the area of low And about 79 percent of landslides are located in high and very high deposition potentials.

  13. Investigating Confusion Between Perceptions of Relationship Education and Couples Therapy

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    Brandon K. Burr

    2017-03-01

    Full Text Available Although relationship education (RE and couples therapy (CT have similar goals in helping build and sustain healthy couple and family relationships, there remains confusion between the focus and structure of the two services. Literature on the marketing of family programs indicates that the awareness level of the target audience should dictate marketing and recruitment messages. Lack of awareness regarding RE and confusion over the difference between RE and CT most likely affects the decision to attend. In order to inform RE recruitment and marketing approaches, this study investigated overall perceptions of RE, RE awareness, and confusion regarding the difference between RE and CT in a sample of 1,977 individuals. Differences in perceptions were also explored by relationship satisfaction and gender. Results showed a fairly high lack of awareness of RE and confusion between RE and CT. Results also showed that respondents in more satisfying relationships see RE less positively, and men see RE less positively than women. Implications for practitioners and researchers are presented.

  14. INVESTIGATING THE RELATIONSHIP BETWEEN ORGANIZATIONAL COMMUNICATION AND ORGANIZATIONAL CULTURE

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    Mădălina ŞOMĂCESCU

    2016-05-01

    Full Text Available In this paper we investigated the relationship between the organizational communication and organizational culture. The starting point of our analysis is that the two variables are in interdependent relation. Our study, performed in a large public organization operating in Romania and abroad, identified a positive association between the two variables. The organizational communication helps the organization to disseminate the culture among the employees. Also, the organizational culture is developed through the interactions and communications among the staff. The management of the organizations must encourage and promote an open communication in order to create a culture that sustain the performance.

  15. Investigation of Relationship Between Parvovirus B19 Infection and Psoriasis

    Directory of Open Access Journals (Sweden)

    Mehmet Yıldırım

    2010-12-01

    Full Text Available Background and Design: Psoriasis is a common, chronic, relapsing skin disease, characterized by the formation of typical scaly papules or plaques. The three factors well-recognized as triggering the onset, causing new lesions or inducing a flare in the disease are: stress, skin injury and infection. Various microorganisms are associated with provocation and/or exacerbation of psoriasis. The aim of this study was to investigate the relationship between parvovirus B19 (PVB19 and psoriasis/psoriasis area severity index (PASI. Material and Method: Sixty patients with psoriasis (36 men, 24 women and 40 healthy volunteers (22 men, 18 women were included in our study. PVB19 DNA was quantified by real-time polymerase chain reaction. Results: PVB19 DNA was detected in 27 of 60 subjects in the patient group (45% and in 9 of 40 controls (22.5% (p0.05. The relationship between the viral load and the subtypes of psoriasis was not statistically significant (p>0.05.Conclusion: According to the results of this study, it was concluded that a relationship may be present between psoriasis and PVB 19 infection.

  16. Reactions of OH radicals with 2-methyl-1-butyl, neopentyl and 1-hexyl nitrates. Structure-activity relationship for gas-phase reactions of OH with alkyl nitrates: An update

    Science.gov (United States)

    Bedjanian, Yuri; Morin, Julien; Romanias, Manolis N.

    2018-05-01

    The kinetics of the reactions 2-methyl-1-butyl (2M1BNT), neopentyl (NPTNT) and 1-hexyl nitrates (1HXNT) with OH radicals has been studied using a low pressure flow tube reactor combined with a quadrupole mass spectrometer. The rate constants of the title reactions were determined under pseudo-first order conditions from kinetics of OH consumption in excess of nitrates. The overall rate coefficients, k2M1BNT = 1.54 × 10-14 (T/298)4.85 exp (1463/T) (T = 278-538 K), kNPTNT = 1.39 × 10-14 (T/298)4.89 exp (1189/T) (T = 278-500 K) and k1HXNT = 2.23 × 10-13 (T/298)2.83 exp (853/T) cm3molecule-1s-1 (T = 306-538 K) (with conservative 15% uncertainty), were determined at a total pressure of 1 Torr of helium. The yield of trimethylacetaldehyde ((CH3)3CCHO), resulting from the abstraction by OH of an α-hydrogen atom in neopentyl nitrate, followed by α-substituted alkyl radical decomposition, was determined as 0.31 ± 0.06 at T = 298 K. The calculated tropospheric lifetimes of 2M1BNT, NPTNT and 1HXNT indicate that reaction of these nitrates with OH represents an important sink of these compounds in the atmosphere. Based on the available kinetic data, we have updated the structure-activity relationship (SAR) for reactions of alkyl nitrates with OH at T = 298 K. Good agreement (within 20%) is obtained between experimentally measured rate constants (total and that for H-atom abstraction from α carbon) and those calculated from SAR using new substituents factors for almost all the experimental data available.

  17. Structure-activity relationships of the unique and potent agouti-related protein (AGRP)-melanocortin chimeric Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH2 peptide template.

    Science.gov (United States)

    Wilczynski, Andrzej; Wilson, Krista R; Scott, Joseph W; Edison, Arthur S; Haskell-Luevano, Carrie

    2005-04-21

    The melanocortin receptor system consists of endogenous agonists, antagonists, G-protein coupled receptors, and auxiliary proteins that are involved in the regulation of complex physiological functions such as energy and weight homeostasis, feeding behavior, inflammation, sexual function, pigmentation, and exocrine gland function. Herein, we report the structure-activity relationship (SAR) of a new chimeric hAGRP-melanocortin agonist peptide template Tyr-c[beta-Asp-His-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) that was characterized using amino acids previously reported in other melanocortin agonist templates. Twenty peptides were examined in this study, and six peptides were selected for (1)H NMR and computer-assisted molecular modeling structural analysis. The most notable results include the identification that modification of the chimeric template at the His position with Pro and Phe resulted in ligands that were nM mouse melanocortin-3 receptor (mMC3R) antagonists and nM mouse melanocortin-4 receptor (mMC4R) agonists. The peptides Tyr-c[beta-Asp-His-DPhe-Ala-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) and Tyr-c[beta-Asp-His-DNal(1')-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) resulted in 730- and 560-fold, respectively, mMC4R versus mMC3R selective agonists that also possessed nM agonist potency at the mMC1R and mMC5R. Structural studies identified a reverse turn occurring in the His-DPhe-Arg-Trp domain, with subtle differences observed that may account for the differences in melanocortin receptor pharmacology. Specifically, a gamma-turn secondary structure involving the DPhe(4) in the central position of the Tyr-c[beta-Asp-Phe-DPhe-Arg-Trp-Asn-Ala-Phe-Dpr]-Tyr-NH(2) peptide may differentiate the mixed mMC3R antagonist and mMC4R agonist pharmacology.

  18. Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

    Science.gov (United States)

    Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

    2016-07-20

    The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

  19. Discovery, characterization and structure-activity relationships of an inhibitor of inward rectifier potassium (Kir channels with preference for Kir2.3, Kir3.X and Kir7.1

    Directory of Open Access Journals (Sweden)

    Jerod S Denton

    2011-11-01

    Full Text Available The inward rectifier family of potassium (Kir channels is comprised of at least 16 family members exhibiting broad and often overlapping cellular, tissue or organ distributions. The discovery of disease-causing mutations in humans and experiments on knockout mice has underscored the importance of Kir channels in physiology and in some cases raised questions about their potential as drug targets. However, the paucity of potent and selective small-molecule modulators targeting specific family members has with few exceptions mired efforts to understand their physiology and assess their therapeutic potential. A growing body of evidence suggests that GIRK (G protein-regulated inward rectifier K channels of the Kir3.X subfamily may represent novel targets for the treatment of atrial fibrillation. In an effort to expand the molecular pharmacology of GIRK, we performed a thallium (Tl+ flux-based high-throughput screen (HTS of a Kir1.1 inhibitor library for modulators of GIRK. One compound, termed VU573, exhibited 10-fold selectivity for GIRK over Kir1.1 (IC50 = 1.9 M and 19 M, respectively and was therefore selected for further study. In electrophysiological experiments performed on Xenopus laevis oocytes and mammalian cells, VU573 inhibited Kir3.1/3.2 (neuronal GIRK and Kir3.1/3.4 (cardiac GIRK channels with equal potency and preferentially inhibited GIRK, Kir2.3 and Kir7.1 over Kir1.1 and Kir2.1. Tl+ flux assays were established for Kir2.3 and the M125R pore mutant of Kir7.1 to support medicinal chemistry efforts to develop more potent and selective analogs for these channels. The structure-activity relationships of VU573 revealed few analogs with improved potency, however two compounds retained most of their activity toward GIRK and Kir2.3 and lost activity toward Kir7.1. We anticipate that the VU573 series will be useful for exploring the physiology and structure-function relationships of these Kir channels.

  20. An Evolution in Research Practice for Investigating International Business Relationships

    Directory of Open Access Journals (Sweden)

    Anne HAMPTON

    2013-09-01

    Full Text Available The purpose of this paper is to discuss the development and rationale of research methodology for a specific topic of research. The topic in question is an investigation into international business relationships, a complex subject and one that is very topical in the growing world of international business. It is intended to examine the logical development of research practice in our study and to show the changing thought processes and justifications we have made over a period of time. It is hoped that this discussion paper will be helpful to academics and students alike, as so often research methodology is only discussed in terms of the final method/techniques chosen with an emphasis on the technical aspects of the methods rather than relating them to the subject to be researched.

  1. Investigation of internet addiction and personality relationship among university students

    Directory of Open Access Journals (Sweden)

    Fatih Özgen

    2017-12-01

    Full Text Available Aim: In this study, it was aimed to examine to internet addiction and personality relation among university students. Material and Methods: Totally 527 students, studying at Çanakkale Onsekiz Mart university participated to this study as a volunteer. Internet addiction scale and Eysenck personality scale were used to collect data. Kruskal Wallis was used to investigate differences between groups and Pearson Correlation was also used to investigate the relation between variables in SPSS. Findings were accepted at p<0.05 level. Results: Total internet addiction scores of participants were 26.85±14.41 point, %94 of them were average internet user. It was determined that they are mostly connected the internet from the mobile phone (%58, 5.8±1.8 days a week and 4.7±3.0 hours a day, and that they mostly use social network and chat sites (%30. There were statistical differences between departments (p<0.05. The internet addiction score of students of Faculty of Science and Literature, School of Health and Theology was significantly lower than other sections. internet addiction scores were higher in males (p<0.05. In terms of personality characteristics of participants, it was found that they had a higher score (3.9±1.8 in the "Outward Turnover". It was determined that there is a statistically positive relationship between internet addiction score and Neurotism, Psychotism but the negative relationship with the "Lie" personality sub-dimensions. Conclusion: Internet dependency score was found low in this study. Although this is a desirable situation, it would be useful to ensure participation of students in the recreational activities to protect this situation.

  2. Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity: in silico bioinformatic step-by-step guide using quantitative structure-activity relationships.

    Science.gov (United States)

    Hattotuwagama, Channa K; Doytchinova, Irini A; Flower, Darren R

    2007-01-01

    Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method

  3. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

    Science.gov (United States)

    Mladenović, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-04-24

    Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including the following: (1) definition of optimized and validated structure-based three-dimensional (3-D) quantitative structure-activity relationships (QSAR) models derived from available cocrystallized inhibitor-MAO B complexes; (2) elaboration of SAR features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61 ) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rule assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSAR training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a

  4. Investigating Valence and Autonomy in Children's Relationships with Imaginary Companions

    Science.gov (United States)

    McInnis, Melissa A.; Pierucci, Jillian M.; Gilpin, Ansley Tullos

    2013-01-01

    Little research has explored valence and autonomy in children's imaginary relationships. In the present study, a new interview (modeled after an existing measure for real relationships) was designed to elicit descriptions of both positive and negative interactions with imaginary companions and to provide a measure of relationship valence and…

  5. Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues.

    Science.gov (United States)

    Vallone, Alessandra; D'Alessandro, Sarah; Brogi, Simone; Brindisi, Margherita; Chemi, Giulia; Alfano, Gloria; Lamponi, Stefania; Lee, Soon Goo; Jez, Joseph M; Koolen, Karin J M; Dechering, Koen J; Saponara, Simona; Fusi, Fabio; Gorelli, Beatrice; Taramelli, Donatella; Parapini, Silvia; Caldelari, Reto; Campiani, Giuseppe; Gemma, Sandra; Butini, Stefania

    2018-04-25

    Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba 2+ current through Ca v 1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. An Investigation of the Relationship between Capital Levels and the ...

    African Journals Online (AJOL)

    Siphambe H (Prof)

    The paper therefore seeks to establish the relationship between capital levels and ... Thus an increase in capital requirements will not affect banks' ..... competitive products and services to customers with the end result being increased ...

  7. Investigation on the Possible Relationship between Magnetic Pulsations and Earthquakes

    Science.gov (United States)

    Jusoh, M.; Liu, H.; Yumoto, K.; Uozumi, T.; Takla, E. M.; Yousif Suliman, M. E.; Kawano, H.; Yoshikawa, A.; Asillam, M.; Hashim, M.

    2012-12-01

    The sun is the main source of energy to the solar system, and it plays a major role in affecting the ionosphere, atmosphere and the earth surface. The connection between solar wind and the ground magnetic pulsations has been proven empirically by several researchers previously (H. J. Singer et al., 1977, E. W. Greenstadt, 1979, I. A. Ansari 2006 to name a few). In our preliminary statistical analysis on relationship between solar and seismic activities (Jusoh and Yumoto, 2011, Jusoh et al., 2012), we observed a high possibility of solar-terrestrial coupling. We observed high tendency of earthquakes to occur during lower phase solar cycles which significantly related with solar wind parameters (i.e solar wind dynamic pressure, speed and input energy). However a clear coupling mechanism was not established yet. To connect the solar impact on seismicity, we investigate the possibility of ground magnetic pulsations as one of the connecting agent. In our analysis, the recorded ground magnetic pulsations are analyzed at different ranges of ultra low frequency; Pc3 (22-100 mHz), Pc4 (6.7-22 mHz) and Pc5 (1.7-6.7 mHz) with the occurrence of local earthquake events at certain time periods. This analysis focuses at 2 different major seismic regions; north Japan (mid latitude) and north Sumatera, Indonesia (low latitude). Solar wind parameters were obtained from the Goddard Space Flight Center, NASA via the OMNIWeb Data Explorer and the Space Physics Data Facility. Earthquake events were extracted from the Advanced National Seismic System (ANSS) database. The localized Pc3-Pc5 magnetic pulsations data were extracted from Magnetic Data Acquisition System (MAGDAS)/Circum Pan Magnetic Network (CPMN) located at Ashibetsu (Japan); for earthquakes monitored at north Japan and Langkawi (Malaysia); for earthquakes observed at north Sumatera. This magnetometer arrays has established by International Center for Space Weather Science and Education, Kyushu University, Japan. From the

  8. An investigation of the relationship between test anxiety and ...

    African Journals Online (AJOL)

    The objective of this study was to determine the relationship between test anxiety and academic performance among students in Nyeri district, Kenya. The correlational study design was used. The study was carried out among form four students together with their teachers. The target population was 83,000 students and ...

  9. Investigation of Relationship between Aggression and Sociometric Popularity in Adolescents

    Science.gov (United States)

    Yavuzer, Yasemin

    2013-01-01

    In this study, it was aimed to determine the linear and curvilinear relationships between adolescent aggression and sociometric popularity. 524 adolescents randomly selected from 20 elementary schools in Nigde city center formed the study group. The participants were from 8th grade in 20 different classrooms. The research data were collected by…

  10. Investigation of the Relationship between Organizational Trust and Organizational Commitment

    Science.gov (United States)

    Bastug, Gülsüm; Pala, Adem; Kumartasli, Mehmet; Günel, Ilker; Duyan, Mehdi

    2016-01-01

    Organizational trust and organizational commitment are considered as the most important entraining factors for organizational success. The most important factor in the formation of organizational commitment is trust that employees have in their organizations. In this study, the relationship between organizational trust and organizational…

  11. AN INVESTIGATION ON THE CUSTOMER RELATIONSHIP MANAGEMENT IN FURNITURE STORES

    Directory of Open Access Journals (Sweden)

    İlker Akyüz

    2004-11-01

    Full Text Available The most valuable thing for corporations is customers in today’s competitive environment. The evaluation obtained with suitable methodology is important vitally in the success of customer relationship management systems applied for the continuous customer satisfaction and devotion. Continuous customer satisfaction, development of communication skills with customers, caring with customers’ desires and compliments before and after sale just in sale time, development of the quality of services being offered to the customers is dependent on the determining customer problems closely and giving customer focused services. In this study, it was tried to reveal the customer relationship management, communication with customer, customer focused sale offered before, after and just in sale time in some furniture stores located in Trabzon. It was found that the furniture stores in Trabzon have been generally trying to give customer focused sale services

  12. Who Helps Whom? Investigating the Development of Adolescent Prosocial Relationships

    Science.gov (United States)

    van Rijsewijk, Loes; Dijkstra, Jan Kornelis; Pattiselanno, Kim; Steglich, Christian; Veenstra, René

    2016-01-01

    We investigated adolescent prosocial relations by examining social networks based on the question "Who helps you (e.g., with homework, with repairing a flat [bicycle] tire, or when you are feeling down?)." The effects of individual characteristics (academic achievement, symptoms of depressive mood, and peer status) on receiving help and…

  13. Investigating the causal relationship between Self Beliefs and ...

    African Journals Online (AJOL)

    This study also investigated the current state of the influence of gender schema on adolescents\\' success aspiration. Data collected were analyzed with the use of ANCOVA and Pearson correlation coefficient. Results obtained indicated a significant effect of self defeating beliefs and negative automatic thoughts in success ...

  14. Using structural equation modeling to investigate relationships among ecological variables

    Science.gov (United States)

    Malaeb, Z.A.; Kevin, Summers J.; Pugesek, B.H.

    2000-01-01

    Structural equation modeling is an advanced multivariate statistical process with which a researcher can construct theoretical concepts, test their measurement reliability, hypothesize and test a theory about their relationships, take into account measurement errors, and consider both direct and indirect effects of variables on one another. Latent variables are theoretical concepts that unite phenomena under a single term, e.g., ecosystem health, environmental condition, and pollution (Bollen, 1989). Latent variables are not measured directly but can be expressed in terms of one or more directly measurable variables called indicators. For some researchers, defining, constructing, and examining the validity of latent variables may be the end task of itself. For others, testing hypothesized relationships of latent variables may be of interest. We analyzed the correlation matrix of eleven environmental variables from the U.S. Environmental Protection Agency's (USEPA) Environmental Monitoring and Assessment Program for Estuaries (EMAP-E) using methods of structural equation modeling. We hypothesized and tested a conceptual model to characterize the interdependencies between four latent variables-sediment contamination, natural variability, biodiversity, and growth potential. In particular, we were interested in measuring the direct, indirect, and total effects of sediment contamination and natural variability on biodiversity and growth potential. The model fit the data well and accounted for 81% of the variability in biodiversity and 69% of the variability in growth potential. It revealed a positive total effect of natural variability on growth potential that otherwise would have been judged negative had we not considered indirect effects. That is, natural variability had a negative direct effect on growth potential of magnitude -0.3251 and a positive indirect effect mediated through biodiversity of magnitude 0.4509, yielding a net positive total effect of 0

  15. Investigations into the relationship between spheromak, solar, and astrophysical plasmas

    International Nuclear Information System (INIS)

    Bellan, P.M.; Hsu, S.C.; Hansen, J.F.; Tokman, M.; Pracko, S.E.; Romero-Talamas, C.A.

    2003-01-01

    Spheromaks offer the potential for a simple, low cost fusion reactor and involve physics similar to certain solar and astrophysical phenomena. A program to improve understanding of spheromaks by exploiting this relationship is underway using (i) a planar spheromak gun and (ii) a solar prominence simulator. These devices differ in symmetry but both involve spheromak technology whereby high-voltage is applied across electrodes linking a bias magnetic flux created by external coils. The planar spheromak gun consists of a co-planar disk and annulus linked by a poloidal bias field. Application of high voltage across the gap between disk and annulus drives a current along the bias field. If the current to flux ratio exceeds the inverse of the characteristic linear dimension, a spheromak is ejected. A distinct kink forms just below the ejection threshold. The solar simulation gun consists of two adjacent electromagnets which generate a 'horse-shoe' arched bias field. A current is driven along this arched field by a capacitor bank. The current channel first undergoes pinching, then writhes, and finally bulges outwards due to the hoop force. (author)

  16. Investigation of spatiotemporal relationship between dengue fever and drought

    Science.gov (United States)

    Lee, Chieh-Han; Yu, Hwa-Lung

    2016-04-01

    Dengue Fever is a vector-borne disease that is transmitted between human and mosquitos in tropical and sub-tropical regions. Previous studies have found significant relationship between the epidemic of dengue cases and climate variables, especially temperature and precipitation. Besides, the natural phenomena (e.g., drought) are considered that significantly drop the number of dengue cases by killing vector's breeding environment. However, in Kaohsiung City, Taiwan, there are evidences that the temporal pattern of dengue is correlated to drought events. Kaohsiung City experienced two main dengue outbreaks in 2002 and 2014 that both years were confirmed with serious drought. Especially in 2014, Kaohsiung City was suffered from extremely dengue outbreak in 2014 that reported the highest number of dengue cases in the history. Otherwise, another nearby city, Tainan City, had reported the biggest outbreak in 2015. This study constructs the spatiotemporal model of dengue incidences and index of drought events (Standardized Precipitation Index, SPI) based on the distributed lag nonlinear model (DLNM). Other meteorological measures are also included in the analysis.

  17. Investigating the relationship between nanomaterial hazard and physicochemical properties

    DEFF Research Database (Denmark)

    Johnston, Helinor; Brown, David; Kermanizadeh, Ali

    2012-01-01

    literature has therefore led us to hypothesise that NM toxicity is dictated by the exposure route due to the acquisition of a surface coating (protein corona) that is determined by the route of entry and physico-chemical properties of the NM. This information can be exploited within the intelligent design...... over time, iii) the physico-chemical characteristics of NMs dictate the composition of the protein corona, and the toxicity of NMs and iv) NMs can affect secondary target sites that vary according to delivery route and corona composition following exposure. These findings, and evidence from the wider...... of NMs in the future (e.g. to control protein adsorption and the subsequent cellular response), and be used to improve the design of toxicology investigations (e.g. to inform how NMs should be dispersed within in vitro experiments to more accurately reflect in vivo conditions)....

  18. An Investigation on the Relationship between Prospective Teachers' Early Teacher Identity and Their Need for Cognition

    Science.gov (United States)

    Arpaci, Dilara; Bardakçi, Mehmet

    2016-01-01

    Investigating the relationship between them can reveal important implications vital for classroom practice in teacher education institutions. Therefore, this study investigated the relationship between pre-service teachers' early teacher identity and their need for cognition. The research data was collected with the sample which consists of 449…

  19. Investigating the Relationship between Effective Communication of Spouse and Father-Child Relationship (Test Pattern Causes to Education Parents)

    Science.gov (United States)

    Ataeifar, Robabeh; Amiri, Sholeh; Ali Nadi, Mohammad

    2016-01-01

    This research is targeted with the plan of father-child model or effective relationship mediating of spouses or investigating attachment style, personality traits, communication skills, and spouses' sexual satisfaction. Based on this, 260 people (father and child) were selected through random sampling method based on share. Participants were…

  20. Building Strong Customer Relationships through Brand Orientation in Small Service Firms: An Empirical Investigation

    OpenAIRE

    Chovancová, Miloslava; Osakwe, Christian Nedu; Ogbonna, Benson U.

    2015-01-01

    The purpose of this paper is to empirically examine the relationship between the adoption of a brand orientation strategy and customer relationship performance in a small service firm setting. More specifically, in addition to investigating the direct link between brand orientation and customer relationship performance, we further examine the moderating effects of entrepreneurial orientation and perceived competitive intensity on the empirical link between brand orientation and customer relat...

  1. Manifesting Resilience in the Secondary School: An Investigation of the Relationship Dynamic in Visual Arts Classrooms

    Science.gov (United States)

    Stride, Yvette; Cutcher, Alexandra

    2015-01-01

    Responding to the literature on positive adaptability, we investigated caring relationships as they manifest as protective processes in the Visual Arts classroom. Caring relationships between teachers and their students have been isolated as one of three protective factors which help promote resilience and thus positive adaptability. The Visual…

  2. A Phenomenological Investigation of Adolescent Dating Relationships and Dating Violence Counseling Interventions

    Science.gov (United States)

    Hays, Danica G.; Michel, Rebecca E.; Cole, Rebekah F.; Emelianchik, Kelly; Forman, Julia; Lorelle, Sonya; McBride, Rebecca; Sikes, April

    2011-01-01

    Despite the prevalence of dating violence, incidences often go unreported due to a lack of awareness among students as to appropriate dating behaviors. This phenomenology investigated how adolescents conceptualize and experience dating relationships. We explored adolescent females' definitions of healthy and abusive relationships, experiences with…

  3. An event-related potential investigation of the relationship between semantic and perceptual levels of representation

    NARCIS (Netherlands)

    Van Schie, H.T.; Wijers, A.A.; Kellenbach, M.L; Stowe, L.A.

    The present study was conducted to investigate relationships between semantic and perceptual levels of representation. A picture - word repetition paradigm was used in which we manipulated the semantic relationship between pictures and words. Experiment I involved two types of trials, one with words

  4. Investigating the Relationship between the Washback Effect of IELTS Test and Iranian IELTS Candidates’ Life Skills

    OpenAIRE

    Ghamarian, Daniel; Motallebzadeh, Khalil; Fatemi, Mohammad

    2014-01-01

    This study aims to investigate the relationship between the washback effect of IELTS test and Iranian IELTS candidates’ life skills pattern as well as investigating the relationship between constructs underlying IELTS test and Iranian IELTS candidates’ communicative skill viewpoints on language proficiency. The correlational research method was employed as the design of the study. The study included 322 Iranian IELTS candidates who completed IELTS preparation courses. To collect data, the res...

  5. Evaluation and structure-activity relationship analysis of a new series of 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines as potential antibacterial agents

    Science.gov (United States)

    Beyzaei, Hamid; Aryan, Reza; Moghaddam-Manesh, Mohammadreza; Ghasemi, Behzad; Karimi, Pouya; Samareh Delarami, Hojat; Sanchooli, Mahmood

    2017-09-01

    The synthesis of pyrazolo[3,4-d]pyrimidine derivatives is important due to their presence in various biologically active compounds such as anticancer, antimicrobial, antiparasitic, anti-inflammatory and antidiabetic agents. In this project, a new and efficient approach for the synthesis of some novel 4-imino-5H-pyrazolo[3,4-d]pyrimidin-5-amines from reaction of 5-amino-pyrazole-4-carbonitrile with various hydrazides in ethanolic sodium ethoxide medium was reported. Antimicrobial activities of all synthesized derivatives were evaluated against eight Gram-positive and five Gram-negative pathogenic bacteria. The moderate to good inhibitory effects were observed based on inhibition zone diameter (IZD), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. In order to determine the reasonable relationship between antibacterial activities and physiochemical properties of the derivatives, computational studies were carried out in terms of geometry optimization, short-range van der Waals forces, dipole moments, atomic charges and frontier orbital energies. It was found that both short-range forces and covalent bonds are important in the observed inhibitory effects of the molecules. The results suggested that pyrazolo[3,4-d]pyrimidine derivatives prefer a soft nucleophilic attack on bio-macromolecular targets. Furthermore, our models proposed that the antibacterial activities of these derivatives can be improved by substituting large electron donating groups on the 6-phenyl rings.

  6. Synthesis and Structure-Activity Relationships of N-Dihydrocoptisine-8-ylidene Aromatic Amines and N-Dihydrocoptisine-8-ylidene Aliphatic Amides as Antiulcerative Colitis Agents Targeting XBP1.

    Science.gov (United States)

    Xie, Meng; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Zhang, Zhi-Hui; Li, Zhi-Hong; Wang, Wen-Jie; Qin, Hai-Lin

    2016-04-22

    In this study, natural quaternary coptisine was used as a lead compound to design and synthesize structurally stable and actively potent coptisine analogues. Of the synthesized library, 13 N-dihydrocoptisine-8-ylidene amines/amides were found not only to be noncytotoxic toward intestinal epithelial cells (IECs), but they were also able to activate the transcription of X-box-binding protein 1 (XBP1) targets to varying extents in vitro. Antiulcerative colitis (UC) activity levels were assessed at the in vitro molecular level as well as in vivo in animals using multiple biomarkers as indices. In an in vitro XBP1 transcriptional activity assay, four compounds demonstrated good dose-effect relationships with EC50 values of 0.0708-0.0132 μM. Moreover, two compounds were confirmed to be more potent in vivo than a positive control, demonstrating a curative effect for UC in experimental animals. Thus, the findings of this study suggest that these coptisine analogues are promising candidates for the development of anti-UC drugs.

  7. Building Strong Customer Relationships through Brand Orientation in Small Service Firms: An Empirical Investigation

    Directory of Open Access Journals (Sweden)

    Miloslava Chovancová

    2015-06-01

    Full Text Available The purpose of this paper is to empirically examine the relationship between the adoption of a brand orientation strategy and customer relationship performance in a small service firm setting. More specifically, in addition to investigating the direct link between brand orientation and customer relationship performance, we further examine the moderating effects of entrepreneurial orientation and perceived competitive intensity on the empirical link between brand orientation and customer relationship performance. To test the hypothesized relationships in the conceptual framework, 105 usable structured questionnaires were collected from small service firms and the data were further analyzed using a hierarchical, moderated regression analysis. The results affirm the positive link between brand orientation and customer relationship performance. Moreover, entrepreneurial orientation is found to strengthen the brand orientation-customer relationship performance link. However, our results show that competitive intensity does not significantly moderate the brand orientation-customer relationship performance link. Nonetheless, it is highly suggestive that perceived competitive intensity is a direct predictor of customer relationship performance. In terms of the practical significance of the overall research model, the effect size is fairly large (Cohen’s f 2 = 0.33. The research implications and directions for future research are further highlighted in the penultimate section of the paper.

  8. Investigate The Relationship Between Brand Equity Brand Loyalty And Customer Satisfaction

    OpenAIRE

    Farbod Souri

    2017-01-01

    The purpose of this study conducted an empirical study in the field of marketing in order to investigate the relationship between brand equity brand loyalty and customer satisfaction in Refah stores in which Nam and colleagues model 2011 have been used. In this model the relationship between brand equity and brand loyalty and customer satisfaction is evaluated. To review research a sample of 384 customers was selected as a stepwise clustering. Data gathered by standard questionnaire with 23 q...

  9. Thapsigargin, origin, chemistry, structure-activity relationships and prodrug development

    DEFF Research Database (Denmark)

    Doan, Thi Quynh Nhu; Christensen, Søren Brøgger

    2015-01-01

    Thapsigargin was originally isolated from the roots of the Mediterranean umbelliferous plant Thapsia garganica in order to characterize the skin irritant principle. The biological activity was related to the subnanomolar affinity for the sarco-endoplasmic reticulum calcium ATPase. Prolonged......) targeted against prostate cancer. Conjugation to a peptide, which only is a substrate for prostate specific membrane antigen enabled development of a prodrug (G202), which is targeted towards a number of cancer diseases including hepatocellular carcinoma. G202 has under the name of mipsagargin in clinical...

  10. Quantitative structure-activity relationships of salicylamide neuroleptic agents.

    Science.gov (United States)

    Gupta, S P; Saha, R N; Singh, P

    1990-05-01

    The in vitro antidopamine activity of substituted N-[(1-alkyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamides was found to be well correlated with the hydrophobic and electronic nature of substituents at the 3-position, and with the steric nature of groups replacing the hydrogen atom of the salicyl hydroxy group. In contrast, only the hydrophobic and steric characteristics were found to be important in the in vivo activity of these neuroleptics. This difference suggests that different mechanisms are probably involved in their in vitro and in vivo actions, and that the relevant receptors are slightly different in structure. The in vitro results suggest that electron donation by the 3-substituent strengthens the formation of a hydrogen bond between the carbonyl group of the amide moiety and a hydrogen of the receptor.

  11. Structure-activity relationships of strychnine analogues at glycine receptors

    DEFF Research Database (Denmark)

    Mohsen, A.M.Y.; Heller, Eberhard; Holzgrabe, Ulrike

    2014-01-01

    Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best...... pharmacological profile exhibiting an IC50 value of 1.6 μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21)[DOUBLE BOND]C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine...

  12. Aromatic-Aromatic Interactions in Biological System: Structure Activity Relationships

    International Nuclear Information System (INIS)

    Rajagopal, Appavu; Deepa, Mohan; Govindaraju, Munisamy

    2016-01-01

    While, intramolecular hydrogen bonds have attracted the greatest attention in studies of peptide conformations, the recognition that several other weakly polar interactions may be important determinants of folded structure has been growing. Burley and Petsko provided a comprehensive overview of the importance of weakly polar interactions, in shaping protein structures. The interactions between aromatic rings, which are spatially approximate, have attracted special attention. A survey of the proximal aromatic residue pairs in proteins, allowed Burley and Petsko to suggest that, “phenyl ring centroids are separated by a preferential distance of between 4.5 and 7 Å, and dihedral angles approximately 90° are most common”

  13. Preliminary structure-activity relationship studies on some novel s ...

    African Journals Online (AJOL)

    yl)-1, 3, 4-oxadiazole-2-thiol were synthesized through reaction with different saturated and unsaturated ... inhibitor, while compound 5b with n-propyl substitution is a strong antibacterial agent. ... sulfonyl chloride (30 mmol) in 30 mL distilled.

  14. Aromatic-Aromatic Interactions in Biological System: Structure Activity Relationships

    Energy Technology Data Exchange (ETDEWEB)

    Rajagopal, Appavu; Deepa, Mohan [Molecular Biophysics Unit, Indian Institute of Sciences-Bangalore, Karnataka (India); Govindaraju, Munisamy [Bio-Spatial Technology Research Unit, Department of Environmental Biotechnology, School of Environmental Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu (India)

    2016-02-26

    While, intramolecular hydrogen bonds have attracted the greatest attention in studies of peptide conformations, the recognition that several other weakly polar interactions may be important determinants of folded structure has been growing. Burley and Petsko provided a comprehensive overview of the importance of weakly polar interactions, in shaping protein structures. The interactions between aromatic rings, which are spatially approximate, have attracted special attention. A survey of the proximal aromatic residue pairs in proteins, allowed Burley and Petsko to suggest that, “phenyl ring centroids are separated by a preferential distance of between 4.5 and 7 Å, and dihedral angles approximately 90° are most common”.

  15. Investigating Years 7 to 12 students' knowledge of linear relationships through different contexts and representations

    Science.gov (United States)

    Wilkie, Karina J.; Ayalon, Michal

    2018-02-01

    A foundational component of developing algebraic thinking for meaningful calculus learning is the idea of "function" that focuses on the relationship between varying quantities. Students have demonstrated widespread difficulties in learning calculus, particularly interpreting and modeling dynamic events, when they have a poor understanding of relationships between variables. Yet, there are differing views on how to develop students' functional thinking over time. In the Australian curriculum context, linear relationships are introduced to lower secondary students with content that reflects a hybrid of traditional and reform algebra pedagogy. This article discusses an investigation into Australian secondary students' understanding of linear functional relationships from Years 7 to 12 (approximately 12 to 18 years old; n = 215) in their approaches to three tasks (finding rate of change, pattern generalisation and interpretation of gradient) involving four different representations (table, geometric growing pattern, equation and graph). From the findings, it appears that these students' knowledge of linear functions remains context-specific rather than becoming connected over time.

  16. Playing to Investigate the Relationship Between Achievement and the Perception of learning

    Directory of Open Access Journals (Sweden)

    Steven Boyd

    2018-03-01

    Full Text Available This paper investigates the relationship between achievement and the perception of enjoyment and learning through the serious game, Playing Property.Playing Property is an audience response game forming the basis of workshops to engage junior high students, of 13 to 15 years old, and enhance their knowledge of property investment. The investigation extends to the analysis of trends in audience response decisions from 14 workshops, conducted over three consecutive years.Emerging findings present significant associations between enjoyment and the perception of learning. The relationship between achievement, measured in accumulated game score, and the responders’ perception of enjoyment is present but less significant. Further analysis supports a deeper relationship between play and learning, one where competition and other game play attributes are more effective in engagement than point scoring or rewarding.A more detailed evaluation may include staged testing of what may be learned and how well that learning endures, in comparison with other forms of teaching.

  17. An Exploratory Investigation of the Role of Parenting Stress in Relationship Focused Intervention

    Science.gov (United States)

    Alquraini, Turki; Mahoney, Gerald

    2015-01-01

    Background: Mothers of young children with Pervasive Developmental Disorders (PDD) and other disabilities (DD) have been reported to experience high levels of stress. This investigation examined the effects of parental stress on mother's participation in a Relationship Focused intervention (RFI). Methods: Mothers and young children who had either…

  18. Investigating the Relationship between Multiple Intelligences and Professional Identity of Iranian EFL Teachers

    Science.gov (United States)

    Alaee, Mitra

    2015-01-01

    The main purpose of the study was to investigate the relationship between Iranian EFL teachers' Professional Identity and their types of Multiple Intelligences. Moreover, it aimed to see the extent to which their multiple intelligences can predict their professional identity. The participants of the study were 137 Iranian EFL teachers teaching in…

  19. Investigating the Relationship among Internet Addiction, Positive and Negative Affects, and Life Satisfaction in Turkish Adolescents

    Science.gov (United States)

    Telef, Bülent Baki

    2016-01-01

    This study investigates the relationships between Internet addiction and the areas of life satisfaction and positive or negative affects in Turkish adolescents. The research sample comprised 358 students studying in the sixth, seventh and eighth grades at four different middle schools in Canakkale city centre during the 2012-2013 academic year, of…

  20. Investigating the Relationship between Internet Addiction and Strengthening Students' Social Skills

    Science.gov (United States)

    Karimzadeh, Nazanin

    2015-01-01

    The present study is about "Investigating the relationship between internet addictions and strengthening students' social skill reinforcement." One of the social elements in all cultures is social skill or ability to communicate with others effectively. One of the factors that affect this skill is addiction to Internet which has recently…

  1. Investigating the Relationship between Iranian EFL Teachers' Autonomy and Their Neuro-Linguistic Programming

    Science.gov (United States)

    Hosseinzadeh, Ehsan; Baradaran, Abdollah

    2015-01-01

    The present study was an attempt to investigate the relationship between English Language Teachers' autonomy and their Neuro-linguistic Programming (NLP). To this end, a group of 200 experienced English language teachers at various language schools in Tehran, inter alia, Asre Zaban Language Academy, were given two questionnaires namely Teaching…

  2. Investigation the Relationship among Language Learning Strategies, English Self-Efficacy, and Explicit Strategy Instructions

    Science.gov (United States)

    Yang, Pei-Ling; Wang, Ai-Ling

    2015-01-01

    The present study aims to investigate the relationship among EFL college learners' language learning strategies, English self-efficacy, and explicit strategy instruction from the perspectives of Social Cognitive Theory. Three constructs, namely language learning strategies, English learning self-efficacy, and explicit strategy instruction, were…

  3. A Mixed-Methods Study Investigating the Relationship between Media Multitasking Orientation and Grade Point Average

    Science.gov (United States)

    Lee, Jennifer

    2012-01-01

    The intent of this study was to examine the relationship between media multitasking orientation and grade point average. The study utilized a mixed-methods approach to investigate the research questions. In the quantitative section of the study, the primary method of statistical analyses was multiple regression. The independent variables for the…

  4. Good mates retain us right: investigating the relationship between mate retention strategies, mate value, and relationship satisfaction.

    Science.gov (United States)

    Salkicevic, Svjetlana; Stanic, Ajana L; Grabovac, Masa T

    2014-12-07

    Mate retention strategies are an important tool in keeping a partner, and their use is determined by the mate value (MV) of the partner one is trying to keep. The type of strategy used is also dependent on one's own MV: mates of lower MV are more prone to exhibiting strategies that are cost-inflicting for their partners, whereas partner-benefiting strategies are used by mates of higher value. The type of strategies used affects relationship satisfaction (RS), and is also affected by the perceived difference in MVs. However, it is unclear how someone's perception of their partner's MV is related to that partner's behavior and their own RS. To this aim, we investigated the relationship between these variables on a sample of 178 couples. Our results showed that benefit-inducing strategies were used more by--and towards--partners of higher MV, and were positively connected with RS. Cost-inflicting strategies were more used by--and towards--partners of lower MV, and were negatively connected with RS. Less MV difference was positively correlated with RS and benefiting strategies, and negatively correlated with cost-inflicting strategies. It seems that good mates use strategies that benefit their partners, which, in turn, make them more valuable and, consequently, their partner more satisfied.

  5. An investigation into the relationship between political activity levels and political market orientation

    DEFF Research Database (Denmark)

    Ormrod, Robert P.; Henneberg, Stephan C.

    2010-01-01

    Purpose - The key objective of this research is to investigate the relationship between party member activity-levels and perceptions of their party's political market orientation. Specifically, it aims to scrutinise the differences in the interplay of attitudinal and behavioural aspects of politi......Purpose - The key objective of this research is to investigate the relationship between party member activity-levels and perceptions of their party's political market orientation. Specifically, it aims to scrutinise the differences in the interplay of attitudinal and behavioural aspects...... of political market orientation. Design/methodology/approach - Using a wide variety of respondent groups within the party, the research draws on an existing conceptualisation of political market orientation and empirically test its relationship with party member activity levels. Three models, plus a baseline...... model, are developed and data from 1,156 questionnaires are used to investigate a structural equation model using the partial least square method. Findings - While the baseline model exhibits a robust pattern of positive relationships between the attitudinal and behavioural constructs, the comparative...

  6. Investigating the Relationships Among Resilience, Social Anxiety, and Procrastination in a Sample of College Students.

    Science.gov (United States)

    Ko, Chen-Yi Amy; Chang, Yuhsuan

    2018-01-01

    This study investigated the relationships among resilience, social anxiety, and procrastination in a sample of college students. Specifically, structural equation modeling analyses were applied to examine the effect of resilience on procrastination and to test the mediating effect of social anxiety. The results of this study suggested that social anxiety partially mediated the relationship between resilience and procrastination. Students with higher levels of resilience reported a lower frequency of procrastination behavior, and resilience had an indirect effect on procrastination through social anxiety. The results of this study clarify the current knowledge of the mixed results on resilience and procrastination behaviors and offer practical learning strategies and psychological interventions.

  7. Conformation of phylogenetic relationship of Penaeidae shrimp based on morphometric and molecular investigations.

    Science.gov (United States)

    Rajakumaran, P; Vaseeharan, B; Jayakumar, R; Chidambara, R

    2014-01-01

    Understanding of accurate phylogenetic relationship among Penaeidae shrimp is important for academic and fisheries industry. The Morphometric and Randomly amplified polymorphic DNA (RAPD) analysis was used to make the phylogenetic relationsip among 13 Penaeidae shrimp. For morphometric analysis forty variables and total lengths of shrimp were measured for each species, and removed the effect of size variation. The size normalized values obtained was subjected to UPGMA (Unweighted Pair-Group Method with Arithmetic Mean) cluster analysis. For RAPD analysis, the four primers showed reliable differentiation between species, and used correlation coefficient between the DNA banding patterns of 13 Penaeidae species to construct UPGMA dendrogram. Phylogenetic relationship from morphometric and molecular analysis for Penaeidae species found to be congruent. We concluded that as the results from morphometry investigations concur with molecular one, phylogenetic relationship obtained for the studied Penaeidae are considered to be reliable.

  8. Investigating the relationship between pressure force and acoustic waveform in footstep sounds

    DEFF Research Database (Denmark)

    Grani, Francesco; Serafin, Stefania; Götzen, Amalia De

    2013-01-01

    In this paper we present an inquiry into of the relationships between audio waveforms and ground reaction force in recorded footstep sounds. In an anechoic room, we recorded several footstep sounds produced while walking on creaking wood and gravel. The recordings were performed by using a pair o...... of sandals embedded with six pressure sensors each. Investigations of the relationships between recorded force and footstep sounds is presented, together with several possible applications of the system.......In this paper we present an inquiry into of the relationships between audio waveforms and ground reaction force in recorded footstep sounds. In an anechoic room, we recorded several footstep sounds produced while walking on creaking wood and gravel. The recordings were performed by using a pair...

  9. 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profile.

    Science.gov (United States)

    Nawrozkij, Maxim B; Rotili, Dante; Tarantino, Domenico; Botta, Giorgia; Eremiychuk, Alexandre S; Musmuca, Ira; Ragno, Rino; Samuele, Alberta; Zanoli, Samantha; Armand-Ugón, Mercedes; Clotet-Codina, Imma; Novakov, Ivan A; Orlinson, Boris S; Maga, Giovanni; Esté, José A; Artico, Marino; Mai, Antonello

    2008-08-14

    A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl- S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L100I mutated RTs) assays, compounds carrying an ethyl/ iso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.

  10. An Investigation of Justice in Supply Chain Trust and Relationship Commitment - An Empirical Study of Pakistan

    Directory of Open Access Journals (Sweden)

    Ziaullah Muhammad

    2015-03-01

    Full Text Available In recent years supply chain integration (SCI has received increasing attention from scholars and practitioners. However, our knowledge of what influences the supply chain integration practice of relationship commitment is still very limited. The objective of this study is to investigate the relationship among supply chain justices (procedural, distributive and interactional, trust and inter-firms relationship commitment in mainland Pakistan. The research variables have considerable importance in the literature of supply chain management (SCM. The conceptual model comprises five hypotheses. Then hypotheses are tested via an empirical study in which data are collected from 170 manufacturers, distributors, suppliers and retailers of main stream spectrum industries in Pakistan. We used exploratory factor analysis (EFA, confirmatory factor analysis (CFA to examine the validity and reliability of the measurement model, and structural equation modeling (SEM to test the hypotheses. The findings delineate that supply chain justices can develop relationship commitment (affective and continuance via establishing trust among supply chain partners. Moreover, this study reveals interesting and useful implications of supply chain justices, trust and relationship commitment for practitioners.

  11. An experimental investigation on relationship between PSFs and operator performances in the digital main control room

    International Nuclear Information System (INIS)

    Park, Jooyoung; Lee, Daeil; Jung, Wondea; Kim, Jonghyun

    2017-01-01

    Highlights: • The relationship between performance shaping factors and operator performances are experimentally investigated. • The experiment includes features of digital main control room. • The result indicates that the operator’s experience level is the most effective on the performance. - Abstract: This study designs an experiment to investigate the relationship between performance shaping factors (PSFs) and operator performances. This study involves selecting three PSFs that are controllable in the experiments: (1) experience, (2) complexity, and (3) urgency. Six scenarios are developed to reflect the PSFs. The experiment involves the participation of licensed operators and the use of an APR1400 simulator. During the experiment, operator performances, such as completion time, error, secondary task, workload, and situation awareness, are measured and collected. The experimental result indicates that the operator’s experience is most effective on the overall performances. The task complexity influences the secondary tasks and situation awareness.

  12. Investigating the Relationship between Learning Styles and ESP Reading Strategies in Academic Setting

    OpenAIRE

    Parviz Ajideh; Mohammad Zohrabi; Kazem Pouralvar

    2018-01-01

    The present study investigated the relationship between Art and Science students’ learning styles and their ESP reading strategies in academic settings. Learning styles are defined as general orientations learners take toward their learning experiences. This notion has recently obtained attention in the area of language learning. Strategies are also defined as specific behaviours or techniques learners employ towards leaning in order to achieve their learning goals. The strategies chosen are ...

  13. Investigating the Effect of Relationship Marketing on Competitive Advantage: Isfahan’s REFAH Chain Stores

    OpenAIRE

    Razieh Gharehbashloni; Mohsen Seify

    2014-01-01

    This study is intended to investigate the effect of relationship marketing on the competitive advantage in the form of the desired pattern or model of this study. Statistical community of this study has been Esfahan’s REFAH chain stores. Collecting data instruments are the accepted stabilized and justifiability (reliability) questionnaires that a total of 150 questionnaires were distributed and a total 114 of them were returned and analyzed. Amos software was used for analyzing of these data....

  14. Investigating the prevalence of personality disorders and its relationship with personality traits among students

    OpenAIRE

    Davod Ghaderi; Ali Mostafaei; Saadi Bayazidi; Mahdi Shahnazari

    2016-01-01

    The present study was aimed to investigate the prevalence of personality disorders and its relationship with personality traits among students. This research was among epidemiological-correlational descriptive studies. Method: For this purpose, 389 male students were selected via a multi-stage cluster sampling method. All subjects completed Millon's personality disorder (1987) and five-factor personality Costaand McCrae's questionnaires (1989). Results: The results showed that the prevalence ...

  15. An Investigation of the Relationship between Autonomous Learning and Lifelong Learning

    Directory of Open Access Journals (Sweden)

    Cengiz Yurdakul

    2016-12-01

    Full Text Available The present study aims to investigate the relationship between autonomous learning and lifelong learning. The study group consists of 657 secondary school students enrolled in three public schools, aged 11 – 16 from Sakarya, Turkey. In this study, relationships between the variables of autonomous learning and lifelong learning and the sub-dimensions of autonomous learning were investigated. Pearson Product Moment Correlation, Partial Correlation methods were utilized in order to investigate these relationships. Autonomous Learning Scale (12 items which was developed by Macaskill and Taylor (2010, was adapted to Turkish by Arslan and Yurdakul (2015 was conducted to measure autonomous learning. Lifelong Learning Scale (14 items which was developed by Kirby, Knapper, Lamon and Egnatoff (2010, was adapted to Turkish by Arslan and Akcaalan (2015 was carried out to assess lifelong learning level. In the light of the research findings, it can be purported that autonomous learning and lifelong learning scores were correlating significantly. According to the existing results, it can be argued that autonomous learning which can be defined as the capacity to take charge of one’s own learning, has a positive interaction with lifelong learning which can be found voice in one’s ongoing, voluntary, and self-motivated learning.

  16. 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.

  17. Investigating Relationships between Reproduction, Immune Defenses, and Cortisol in Dall Sheep.

    Science.gov (United States)

    Downs, Cynthia J; Boan, Brianne V; Lohuis, Thomas D; Stewart, Kelley M

    2018-01-01

    Life-history theory is fundamental to understanding how animals allocate resources among survival, development, and reproduction, and among traits within these categories. Immediate trade-offs occur within a short span of time and, therefore, are more easily detected. Trade-offs, however, can also manifest across stages of the life cycle, a phenomenon known as carryover effects. We investigated trade-offs on both time scales in two populations of Dall sheep ( Ovis dalli dalli ) in Southcentral Alaska. Specifically, we (i) tested for glucocorticoid-mediated carryover effects from the breeding season on reproductive success and immune defenses during parturition and (ii) tested for trade-offs between immune defenses and reproduction within a season. We observed no relationship between cortisol during mating and pregnancy success; however, we found marginal support for a negative relationship between maternal cortisol and neonate birth weights. Low birth weights, resulting from high maternal cortisol, may result in low survival or low fecundity for the neonate later in life, which could result in overall population decline. We observed a negative relationship between pregnancy and bacterial killing ability, although we observed no relationship between pregnancy and haptoglobin. Study site affected bactericidal capacity and the inflammatory response, indicating the influence of external factors on immune responses, although we could not test hypotheses about the cause of those differences. This study helps advance our understanding of the plasticity and complexity of the immune system and provides insights into the how individual differences in physiology may mediate differences in fitness.

  18. Investigating Relationships between Reproduction, Immune Defenses, and Cortisol in Dall Sheep

    Directory of Open Access Journals (Sweden)

    Cynthia J. Downs

    2018-01-01

    Full Text Available Life-history theory is fundamental to understanding how animals allocate resources among survival, development, and reproduction, and among traits within these categories. Immediate trade-offs occur within a short span of time and, therefore, are more easily detected. Trade-offs, however, can also manifest across stages of the life cycle, a phenomenon known as carryover effects. We investigated trade-offs on both time scales in two populations of Dall sheep (Ovis dalli dalli in Southcentral Alaska. Specifically, we (i tested for glucocorticoid-mediated carryover effects from the breeding season on reproductive success and immune defenses during parturition and (ii tested for trade-offs between immune defenses and reproduction within a season. We observed no relationship between cortisol during mating and pregnancy success; however, we found marginal support for a negative relationship between maternal cortisol and neonate birth weights. Low birth weights, resulting from high maternal cortisol, may result in low survival or low fecundity for the neonate later in life, which could result in overall population decline. We observed a negative relationship between pregnancy and bacterial killing ability, although we observed no relationship between pregnancy and haptoglobin. Study site affected bactericidal capacity and the inflammatory response, indicating the influence of external factors on immune responses, although we could not test hypotheses about the cause of those differences. This study helps advance our understanding of the plasticity and complexity of the immune system and provides insights into the how individual differences in physiology may mediate differences in fitness.

  19. Investigating the Relationship between Social Damages and the Quality of Life in Yazd City

    Directory of Open Access Journals (Sweden)

    M AfkhamiAghda

    2016-06-01

    Full Text Available Introduction: Social damages as a serious threat will serionsly jeopardize people health. Different factors including uncontrolled population growth, urban development, mechanization of life, disruption of interrelationships, etc. are some causes of social damages that might affect the quality of life. This study was conducted with the aim of investigating the relationship between social damages on the quality of life in Yazd city. Methods: This study is a descriptive survey one. The target population of this study was the families living in Yazd city. According to Krejcie and Morgan (1970 the sample size was 384. The samples were selected through cluster sampling. A 42-item pathology questionnaire and a 26-item quality of life questionnaire were used to collect the data. The data were analyzed using SPSS.16 software. Pearson correlation coefficient and analysis of variance were used. Results: The results showed that %95.3 of cases had a low tendency to social damages and there was a significant relationship between social damages and the quality of life. There was also a significant relationship between social damages such as theft, violence, drug abuse, sexual issues, suicide, running from home and quality of life. Conclusion: The results showed that there was a significant relationship between social damages and the quality of life, which it causes numerous problems for the society and it can have a negative effect on the people’s mental and physical health and decreases the quality of life.

  20. Investigations on the structure – Property relationships of electron beam welded Inconel 625 and UNS 32205

    International Nuclear Information System (INIS)

    Devendranath Ramkumar, K.; Sridhar, R.; Periwal, Saurabh; Oza, Smitkumar; Saxena, Vimal; Hidad, Preyas; Arivazhagan, N.

    2015-01-01

    Highlights: • Joining of dissimilar metals of Inconel 625 and UNS S32205 using electron beam welding. • Detailed structure – property relationship of dissimilar welds. • Improved metallurgical and tensile properties from the EB welding. - Abstract: The metallurgical and mechanical properties of electron beam welded Ni based superalloy Inconel 625 and UNS S32205 duplex stainless steel plates have been investigated in the present study. Interface microstructure studies divulged the absence of any grain coarsening effects or the formation of any secondary phases at the heat affected zone (HAZ) of the electron beam (EB) weldments. Tensile studies showed that the fracture occurred at the weld zone in all the trials and the average weld strength was reported to be 850 MPa. Segregation of Mo rich phases was witnessed at the inter-dendritic arms of the fusion zone. The study recommended the use of EB welding for joining these dissimilar metals by providing detailed structure – property relationships

  1. Investigation of Causal Relationship between Stock Prices and Trading Volume using Toda and Yamamoto Procedure

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    Sushil BAJAJ

    2014-11-01

    Full Text Available The present study probes the relationship between the stock prices and trading volume. For achieving this purpose, daily data of adjusted closing stock prices, trading volume of 39 individual securities and S&P CNX Nifty from January 1, 1998 to May 31, 2013 have been used. In this study, instead of applying ordinary Granger causality test to investigate the relationship between stock prices and trading volume, Toda and Yamamoto (1995 procedure has been applied for analyzing the data. Lag length chosen by AIC and FPE criterion has been insured by running Lagrange Multiplier (LM test and causality determined by Toda and Yamamoto test has also been confirmed by using VAR methodology. Although, Toda and Yamamoto and VAR test produced little dissimilar results, nevertheless, the empirical analysis provides sufficient grounds to declare the presence of interaction between stock prices and trading volume.

  2. Investigating the Effect of the Relationship Marketing Tactics on Customer’s Loyalty

    Directory of Open Access Journals (Sweden)

    Mohammad Abasi Niko

    2015-03-01

    Full Text Available The current study attempts to investigate the effect of the relationship marketing tactics on the customer’s loyalty. The present study has applied objective, is descriptive in nature, and is a survey. To analyze the data SPSS 19 and LISREL 8/8 software were used. The target population was the staff of the State University of Ilam, which has a population of 4620 people. The number of sample is equal to 353 according to KrejcieMorgan Table. (Cronbach’s alpha for the entire equation was .906. Considering the influence of independent variants (quality of service, price perception, brand perception, value proposition, consumers’ trust, and customers’ satisfaction on customer loyalty, ten hypotheses were formed, all of which were approved by average to high confidence. The more the level of relationship marketing tactics, the more the quality of relations with customers, which ultimately leads to customer loyalty.

  3. An investigation on relationship between employees’ job satisfaction and organizational commitment

    Directory of Open Access Journals (Sweden)

    Hamzeh Samadi Miarkolaei

    2014-04-01

    Full Text Available Job satisfaction is normally referred to cognitive, affective and evaluative reactions or attitude and state, which is a pleasurable or positive emotional state resulting from the appraisal of one’s job or experience. Organizational commitment has been defined as the extent where an individual accepts, internalizes, and views his/her role based on organizational values and objectives. The purpose of present research is to investigate the relationship between employees’ job satisfaction and organizational commitment of Red Crescent Society’s Textile Industries of Islamic Republic of Iran. (N=180 and n=106. Minnesota Satisfaction Questionnaire (MSQ and Allen and Meyer’s Organizational Commitment Questionnaires are used for collecting data. There were significant relationships between employees’ job satisfaction, organizational commitment, and their dimensions as descripted in results and conclusion.

  4. Investigation of mean glandular dose versus compressed breast thickness relationship for mammography

    International Nuclear Information System (INIS)

    Bor, D.; Tukel, S.; Olgar, T.; Toklu, T.; Aydin, E.; Akyol, O.

    2008-01-01

    The relationship between the mean glandular dose (MGD) and the compressed breast thickness (CBT) is commonly used for the presentation of mammographic dose survey results and could also be useful for the assessment of individual breast doses retrospectively in case of lack of necessary dosimetric instrumentation. The high data scattering from the best fit reduces the reliability of this technique. The aim of this study was to investigate the accuracy of this relationship using the data collected from a patient survey and phantom experiment. Patients were divided into three different groups according to their breast glandularities, which were predicted from the inspection of previous mammograms. X-ray beam qualities that will be used in patient examinations were determined according to breast thickness and predicted glandularities. The MGD versus CBT relationship for all the examined patients resulted in a poor correlation (R 2 = 0.28). This relationship was separately obtained for each glandularity group and also for sub-groups of specific beam qualities. The best correlation (R 2 = 0.73) was obtained for the fatty breast group and Mo/Mo combination. A low correlation (R 2 = 0.34) was observed in the mid-glandularity group due to inclusion of a wide range of glandularities in this group. In the case of the dense breast group, although the glandularity range was narrow, there were e still high data scattering (R 2 = 0.25). This was probably due to the use of Mo/Rh and Mo/Mo combinations. This is validated by obtaining the MGD-CBT relationship specific to Mo/Mo combination (R 2 = 0.61). (authors)

  5. An Investigation of the Relationship between Reading Disabilities and Oral Syntax and the Temporal Aspects of that Relationship.

    Science.gov (United States)

    Dumas, Marsha Rose

    Fifteen eight- and nine-year-old boys with reading disabilities and 15 with normal reading ability participated in a study of the relationships among reading disabilities, oral syntax, and temporal functioning ability (sequencing and the ability to perceive relationships in time). Each subject was given an individual battery of tests which…

  6. A Study to Investigate the Effect of Customer Value on Customer Satisfaction, Brand Loyalty and Customer Relationship Management Performance

    OpenAIRE

    Berrin Onaran,; Zeki Atil Bulut,; Alparslan Ozmen

    2013-01-01

    Beyond satisfying needs, customer value is the key to establish and maintain long run relationships. Hence, providing excellent customer value as a driving force of customer relationships management performance plays a key role in gaining sustainable competitive advantage. The aim of this research is to investigate the relationships among dimensions of customer value, customer satisfaction, brand loyalty and customer relationship management performance. Data obtained from customers of thermal...

  7. Investigation of the relationship between dermoscopic features and histopathological prognostic indicators in patients with cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Özlem Özbağçıvan

    2015-09-01

    Full Text Available Background and Design: Dermoscopy has an important role in the diagnosis of melanoma nowadays. Dermoscopic findings of melanoma had been associated with Breslow thickness and invasion status in previous studies but the relationship between dermatoscopic findings and other histopathological prognostic indicators has not been investigated until today. In this study, our aim is to investigate the relationship between dermatoscopic findings and histopathologic prognostic indicators such as Breslow thickness, invasion status, mitotic rate, lymphovascular invasion (LVI, ulceration and regression in patients who had been diagnosed with melanoma due to their clinical, dermatoscopic and histopatological findings. Materials and Methods: Dermoscopic and histopathological findings of 47 cases of melanoma who applied to our clinic between the years 2000 and 2014 were evaluated. The relationship between the dermoscopic findings which had been reported to be observed in melanomas in previous research and the histopathologic prognostic indicators such as Breslow thickness, invasion status, mitotic rate, lymphovascular invasion, ulceration and regression were investigated. Results: Irregular dots/globules, atypical pigment network, multifocal hypopigmentation, radial streaks and moth-eaten borders have been associated with good prognostic indicators whereas comedo like openings, regular blotch, exophytic papillary structures, dotted, glomerular, lineer irregular vessels, pink/red and blue/gray colors were associated with poor prognostic indicators. Additionally some dermatoscopic findings which are more observed in benign lesions such as multiple milia-like cysts, comedo like openings, moth-eaten borders, regular blotch, exophytic papillary structures and finger print areas have been observed in melanomas in our study. Conclusion: Many dermoscopic findings have demonstrated statistically significant association with the histopathological prognostic indicators

  8. Mind-ception: Investigating the relationship between theory of mind and decision making

    OpenAIRE

    Ahamed, Hassan; Kurczek, Jake

    2016-01-01

    Ahamed, H., & Kurczek, J. (2016, April). Mind-ception: Investigating the relationship between theory of mind and decision making. Poster Presentation at the 31st Annual LVAIC Undergraduate Psychology Conference. Bethlehem, PA. •  Much of our decision making (DM) requires either direct or indirect considerations of others’ thoughts (McCubbins, et al., 2012). •  Theory of Mind (ToM – the capacity to infer the thoughts/intentions of others) is an abi...

  9. Investigation of relationship marketing in the franchising activity of trade companies

    OpenAIRE

    Lisun, Yanina

    2017-01-01

    The article reveals the essence and constituents of the concepts of «relationship», «interaction», «marketing relations», «marketing partnership», «partnership» of the trade business. The essence of the terms «distribution» and «franchising» is investigated and the place of franchising in the structure of organizational and legal forms of distribution systems is determined.It analyses the activity of trading companies and the franchising market of Ukraine is conducted. The article analyses ma...

  10. Investigating the relationships between chronic ill health and educational outcomes in children

    Directory of Open Access Journals (Sweden)

    Michael Fleming

    2017-04-01

    Compared to peers, children who had ADHD or depression were most adversely affected experiencing poorer educational outcomes in all five of the educational domains investigated. Children with epilepsy experienced poorer outcomes across four domains. Children with diabetes and asthma experienced more absence and increased SEN and asthmatic children experienced poorer attainment. Children who have these chronic illnesses at school appear to be at an educational disadvantage therefore further understanding of the intricate relationships between health and education is an on-going important area of public health.

  11. Investigating the asymmetric relationship between inflation-output growth exchange rate changes

    Science.gov (United States)

    Chu, Jenq Fei; Sek, Siok Kun

    2017-08-01

    The relationship between inflation-output growth or output variation has long been studied. In this study, we extend the investigation under two exchange rate flexibility/regime in four Asian countries (Indonesia, Korea, Philippines and Thailand) that have experienced drastic exchange rate regime changes aftermath the financial crisis of 1997. These countries have switched from fixed/rigid exchange rate regime to flexible exchange rate and inflation targeting (IT) regime after the crisis. Our main objective is to compare the inflation-output trade-off relationship in the pre-IT and post-IT periods as a tool to evaluate the efficiency of monetary policy. A nonlinear autoregressive distributed lags (NARDL) model is applied to capture the asymmetric effects of exchange rate changes (increases and decreases). The data ranging from 1981M1 onwards till 2016M3. Our results show that exchange rate has asymmetric effect on inflation both short-run and long-run with larger impact in the post-IT period under flexible regime. Depreciation of exchange rate has leads to higher inflation. Furthermore, we find evidences on the relationship between inflation and growth in both short-run and long-run, but the trade-off only detected in the short run both in the pre- and post-IT periods.

  12. Relationships within Cladobranchia (Gastropoda: Nudibranchia) based on RNA-Seq data: an initial investigation.

    Science.gov (United States)

    Goodheart, Jessica A; Bazinet, Adam L; Collins, Allen G; Cummings, Michael P

    2015-09-01

    Cladobranchia (Gastropoda: Nudibranchia) is a diverse (approx. 1000 species) but understudied group of sea slug molluscs. In order to fully comprehend the diversity of nudibranchs and the evolution of character traits within Cladobranchia, a solid understanding of evolutionary relationships is necessary. To date, only two direct attempts have been made to understand the evolutionary relationships within Cladobranchia, neither of which resulted in well-supported phylogenetic hypotheses. In addition to these studies, several others have addressed some of the relationships within this clade while investigating the evolutionary history of more inclusive groups (Nudibranchia and Euthyneura). However, all of the resulting phylogenetic hypotheses contain conflicting topologies within Cladobranchia. In this study, we address some of these long-standing issues regarding the evolutionary history of Cladobranchia using RNA-Seq data (transcriptomes). We sequenced 16 transcriptomes and combined these with four transcriptomes from the NCBI Sequence Read Archive. Transcript assembly using Trinity and orthology determination using HaMStR yielded 839 orthologous groups for analysis. These data provide a well-supported and almost fully resolved phylogenetic hypothesis for Cladobranchia. Our results support the monophyly of Cladobranchia and the sub-clade Aeolidida, but reject the monophyly of Dendronotida.

  13. Investigating the buyer-seller relationships in the economic recession: A qualitative approach

    Directory of Open Access Journals (Sweden)

    Irene Samanta

    2016-05-01

    Full Text Available The research paper described the in-depth interviews used in investigating the buyer-seller relationships in the e-commerce world during the economic recession in Greece. The data collected from these interviews were analyzed. The qualitative research findings identified how B2B e-commerce has started to change the future of the participating organizations in Greece. Οn the one hand, a number of benefits have occurred from the development of e-business and on the other hand B2B firms need to adopt an innovation culture and redefine  their relationships with their partners from the e-marketing point of view in order to survive in the rapidly changing environment. The results of this research are used to assist the author in the future  to examine a larger sample of B2B firms in order to validate the intention of companies to move from the traditional environment and to establish e-relationships in an e-business context.

  14. The closer the relationship, the more the interaction on facebook? Investigating the case of Taiwan users.

    Science.gov (United States)

    Hsu, Chiung-Wen Julia; Wang, Ching-Chan; Tai, Yi-Ting

    2011-01-01

    This study argues for the necessity of applying offline contexts to social networking site research and the importance of distinguishing the relationship types of users' counterparts when studying Facebook users' behaviors. In an attempt to examine the relationship among users' behaviors, their counterparts' relationship types, and the users' perceived acquaintanceships after using Facebook, this study first investigated users' frequently used tools when interacting with different types of friends. Users tended to use less time- and effort-consuming and less privacy-concerned tools with newly acquired friends. This study further examined users' behaviors in terms of their closeness and intimacy and their perceived acquaintanceships toward four different types of friends. The study found that users gained more perceived acquaintanceships from less close friends with whom users have more frequent interaction but less intimate behaviors. As for closer friends, users tended to use more intimate activities to interact with them. However, these activities did not necessarily occur more frequently than the activities they employed with their less close friends. It was found that perceived acquaintanceships with closer friends were significantly lower than those with less close friends. This implies that Facebook is a mechanism for new friends, rather than close friends, to become more acquainted.

  15. Investigate The Relationship Between Brand Equity Brand Loyalty And Customer Satisfaction

    Directory of Open Access Journals (Sweden)

    Farbod Souri

    2017-06-01

    Full Text Available The purpose of this study conducted an empirical study in the field of marketing in order to investigate the relationship between brand equity brand loyalty and customer satisfaction in Refah stores in which Nam and colleagues model 2011 have been used. In this model the relationship between brand equity and brand loyalty and customer satisfaction is evaluated. To review research a sample of 384 customers was selected as a stepwise clustering. Data gathered by standard questionnaire with 23 questions that its validity and reliability confirmed and was distributed among the statistical population. Data analysis was performed using descriptive statistics and inferential statistics. At the level of Descriptive statistics indices such as frequency and frequency percentage were used and in inferential statistics correlation methods structural equation modeling path analysis has been done using the spss and lisrel software. The results of the analysis showing the existence of a significant and positive relationship of brand equity on customer satisfaction and loyalty. In general the ability of Refah store to increase customer satisfaction and brand loyalty of customers to Refah brand being associated with the brand equity 050 p.

  16. An investigation on relationship between residual income and internal and external performance measures

    Directory of Open Access Journals (Sweden)

    Hesam Daryani

    2012-09-01

    Full Text Available During the past few years, there have been growing interest in learning the relationship between residual income and other financial figures such as dividend per share, market value and operating cash flow. The proposed study of this paper gathers the financial information of all listed firms traded in Tehran Stock Exchange over the period of 2007-2011. We only concentrate on listed companies whose fiscal years started from March to May of each year. The other criterion associated with the proposed study of this paper is that shares of the selected firms must have been active during period of study and there must be no change in their fiscal calendar. The study does not include the shares of holdings, banks, insurance firms. Finally, the information of the firms must be available for course of study. The study uses two regressions analysis and examines five hypotheses including the relationship between residual income and other factors including dividend per share, value added operating cash flow, value added cash flow, market cap and market value added. Using two regression models, all these hypotheses are investigated and the results of the survey confirm a meaningful relationship between residual income and dividend per share, value added operating cash flow, value added cash flow. However, the results of the second model do not confirm the last two hypotheses.

  17. Investigation on the Relationship between Information Communication Technology and Reading Literacy for Northeast Asian Students

    Directory of Open Access Journals (Sweden)

    Lai Yi-Horng

    2016-01-01

    Full Text Available The purpose of this study was to investigate the relationship of internet communication technologies (ICT usage and reading literacy of Northeast Asian Students in PISA 2009. ICT was crucial for all governments in the world towards promoting equity. ICT had been considered a low cost opportunity towards equalizing educational systems. A multilevel modelling (MLM was applied to identify at which school-level the largest variations in the three indicators exist in this study. With MLM, it could be examine simultaneously the effects of different hierarchical school-level variables; to take account of possible correlations of students’ reading literacy in this study within higher levels (Urbanization, Total number of students Computers for education which may otherwise lead to incorrect standard errors and inefficient estimates; to treat higher levels as related; and to examine inter-area variations at each level. The empirical results include the different between group components was significant. Self-confidence in ICT high level tasks was positive with students’ reading literacy, and self-confidence in ICT high level tasks was negative with students’ reading literacy. The urbanization of schools’ area and total number of students of schools were positive with students’ reading literacy. The urbanization of schools’ area was negative with the relationship of ICT for school related tasks and students’ reading literacy. Total number of students was negative with the relationship of ICT for school related tasks and students’ reading literacy, and ICT availability in school and students’ reading literacy.

  18. Investigating the Relationship between Self-Esteem and Postpartum Blues among Delivered Women

    Directory of Open Access Journals (Sweden)

    Masoumeh Sharifzadeh

    2018-04-01

    Full Text Available Postpartum period is the most risky time for mental and psychological disorders including sadness, depression and psychosis. Postpartum depression is the most common postpartum disorder that may disturb relationship of mother with child and family and in the absence of appropriate attention and treatment may have irreparable damages. Therefore, the purpose of this study is investigating the relationship between self-esteem and postpartum depression. This study is cross-sectional and descriptive-analytic and was conducted in 2014 with 322 available samples from the research population, consisted of women who gave birth at Mobini Hospital, Sabzevar. The data collection tools were demographic and midwifery questionnaire, Edinburgh Postnatal Depression Scale, and Rosenberg’s Self-Esteem Scale. Questionnaire within the first 24 hours after giving birth, in the situation where the mother was able to answer the questions, on the third, seventh and tenth day after childbirth, were completed. Then the data were analyzed using SPSS 18 and descriptive and Pearson tests, T-test, and Chi-squared test. The significance level was considered (p=0.05. Blues of giving birth in different days did not differ significantly (p > 05. The relationship between self-esteem and postpartum depression was significant (p < 0.001. Results showed that increased self-esteem in pregnant women results in a reduction in postpartum depression.

  19. Investigating the relationship between leader behaviours and group cohesion within women's walking groups.

    Science.gov (United States)

    Caperchione, Cristina; Mummery, W Kerry; Duncan, Mitch

    2011-07-01

    Early research has shown that leadership behaviour is viewed as a crucial factor in successfully developing team cohesion, effectively resulting in greater team satisfaction and more positive team outcomes. However, little is understood if these same factors have an impact on physical activity groups. The purpose of this study was to investigate the relationship between leader behaviours and group cohesiveness within women's physical activity groups. Participants (N = 95) included a sub-sample of adult women who were previously involved in a women's physical activity/walking program. Participants assessed their groups' leader behaviour using items pertaining to enthusiasm, motivation, instruction and availability, and their groups' cohesiveness using the Physical Activity Group Environment Questionnaire (PAGEQ). Canonical correlation analysis was used to determine the strength of association between the four concepts of group cohesion (ATG-T, ATG-S, GI-T and GI-S) and the four items pertaining to leadership behaviour. A significant multivariate relationship was revealed between group cohesion and leadership behaviour, Wilks' lambda = 0.43, F(16,170) = 5.16, p cohesion. Although a cause-effect relationship cannot be determined, the current study can serve as a valuable template in guiding future research in examining potential mechanisms that may assist with physical activity sustainability. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  20. An empirical investigation on relationship between social capital and organizational commitment

    Directory of Open Access Journals (Sweden)

    Ali Alikhani

    2014-02-01

    Full Text Available This paper presents an empirical investigation to study the relationship between social capital and organizational commitment. The study considers the relationship between social capital with three components of organizational commitment; namely, affective commitment, continuous and normative commitment. The study has been applied among a sample of 292 regular employees who worked for an Iranian bank located in city of Tehran, Iran. The implementation of Pearson correlation has indicated that there were positive and meaningful relationships between social capital and affective commitment (r = 0.197, Sig. = 0.01, continuous (r = 0.308, Sig. = 0.01 and normative commitment (r = 0.423, Sig. = 0.01. In addition, the study has detected that women had more commitment on their organization than men did. The proposed study of this paper has also considered a regression model where organizational commitment is dependent variable and trust and communication are considered as independent variables. According to the results of regression analysis, an increase of one unit in trust and social capital communication will increase organizational commitment by 0.189 and 0.204, respectively.

  1. Investigating the Influence Relationship Models for Stocks in Indian Equity Market: A Weighted Network Modelling Study.

    Science.gov (United States)

    Bhattacharjee, Biplab; Shafi, Muhammad; Acharjee, Animesh

    2016-01-01

    The socio-economic systems today possess high levels of both interconnectedness and interdependencies, and such system-level relationships behave very dynamically. In such situations, it is all around perceived that influence is a perplexing power that has an overseeing part in affecting the dynamics and behaviours of involved ones. As a result of the force & direction of influence, the transformative change of one entity has a cogent aftereffect on the other entities in the system. The current study employs directed weighted networks for investigating the influential relationship patterns existent in a typical equity market as an outcome of inter-stock interactions happening at the market level, the sectorial level and the industrial level. The study dataset is derived from 335 constituent stocks of 'Standard & Poor Bombay Stock Exchange 500 index' and study period is 1st June 2005 to 30th June 2015. The study identifies the set of most dynamically influential stocks & their respective temporal pattern at three hierarchical levels: the complete equity market, different sectors, and constituting industry segments of those sectors. A detailed influence relationship analysis is performed for the sectorial level network of the construction sector, and it was found that stocks belonging to the cement industry possessed high influence within this sector. Also, the detailed network analysis of construction sector revealed that it follows scale-free characteristics and power law distribution. In the industry specific influence relationship analysis for cement industry, methods based on threshold filtering and minimum spanning tree were employed to derive a set of sub-graphs having temporally stable high-correlation structure over this ten years period.

  2. The use of genetic markers to estimate relationships between dogs in the course of criminal investigations.

    Science.gov (United States)

    Ciampolini, Roberta; Cecchi, Francesca; Spinetti, Isabella; Rocchi, Anna; Biscarini, Filippo

    2017-08-17

    Attacks on humans by dogs in a pack, though uncommon, do happen, and result in severe, sometimes fatal, injuries. We describe the role that canine genetic markers played during the investigation of a fatal dog-pack attack involving a 50-year-old male truck driver in a parking lot in Tuscany (Italy). Using canine specific STR genetic markers, the local authorities, in the course of their investigations, reconstructed the genetic relationships between the dogs that caused the deadly aggression and other dogs belonging to the owner of the parking who, at the moment of the aggression, was located in another region of Italy. From a Bayesian clustering algorithm, the most likely number of clusters was two. The average relatedness among the dogs responsible for the aggression was higher than the average relatedness among the other dogs or between the two groups. Taken together, all these results indicate that the two groups of dogs are clearly distinct. Genetic relationships showed that the two groups of dogs were not related. It was therefore unlikely that the murderous dogs belonged to the owner of the parking lot who, on grounds of this and additional evidence, was eventually acquitted.

  3. Investigating the relationship between employees’ career anchors and their psychosocial employability attributes in a financial company

    Directory of Open Access Journals (Sweden)

    Rudolf M. Oosthuizen

    2014-10-01

    Research purpose: The objective of the study was to investigate the relationship between employees’ career anchors and their psychosocial employability attributes as important career meta-capacities in contemporary career development. The study also investigated whether individuals from different age and race groups differed significantly regarding these career meta-capacities. Motivation for the study: Career management has become essential in the contemporary workplace for employees to sustain their employability. Research points to the importance of psychosocial career meta-capacities in helping employees to manage their career development and employability. Research design, approach and method: A cross-sectional quantitative survey using primary data was conducted on a non-probability purposive sample (N = 108 of full-time employees (67% women; 78% 26–45 years old; 78% black employees at a South African financial company. Correlations and Scheffé’s post-hoc test were performed to achieve the research objectives. Main findings: Significant positive relationships were observed between the participants’ career anchors and their psychosocial employability attributes. Age and race groups differed significantly only in terms of their career anchors. Practical/managerial implications: Career management practices in the organisation should accommodate the differences in career orientations and how these relate to the psychosocial employability attributes of their employees. Contribution: The findings add potentially important insights that may inform human resource practices aimed at enhancing the career development and employability of employees and addressing the career needs of different age and race groups.

  4. A Call to Investigate the Relationship Between Education and Health Outcomes Using Big Data.

    Science.gov (United States)

    Chahine, Saad; Kulasegaram, Kulamakan Mahan; Wright, Sarah; Monteiro, Sandra; Grierson, Lawrence E M; Barber, Cassandra; Sebok-Syer, Stefanie S; McConnell, Meghan; Yen, Wendy; De Champlain, Andre; Touchie, Claire

    2018-06-01

    There exists an assumption that improving medical education will improve patient care. While seemingly logical, this premise has rarely been investigated. In this Invited Commentary, the authors propose the use of big data to test this assumption. The authors present a few example research studies linking education and patient care outcomes and argue that using big data may more easily facilitate the process needed to investigate this assumption. The authors also propose that collaboration is needed to link educational and health care data. They then introduce a grassroots initiative, inclusive of universities in one Canadian province and national licensing organizations that are working together to collect, organize, link, and analyze big data to study the relationship between pedagogical approaches to medical training and patient care outcomes. While the authors acknowledge the possible challenges and issues associated with harnessing big data, they believe that the benefits supersede these. There is a need for medical education research to go beyond the outcomes of training to study practice and clinical outcomes as well. Without a coordinated effort to harness big data, policy makers, regulators, medical educators, and researchers are left with sometimes costly guesses and assumptions about what works and what does not. As the social, time, and financial investments in medical education continue to increase, it is imperative to understand the relationship between education and health outcomes.

  5. INVESTIGATING THE RELATIONSHIP BETWEEN PERCEIVED SACRIFICE AND B TO B CUSTOMER SATISFACTION IN THE INSURANCE INDUSTRY

    Directory of Open Access Journals (Sweden)

    Petrisoaia Carmen

    2012-07-01

    Full Text Available The Romanian insurance market expanded rapidly during the last two decades. Presently, the Insurance Supervisory Commission (CSA reports 43 insurance companies and 567 insurance brokers. In this extremely dynamic and competitive environment, it is compulsory to control key elements that generate and maintain customer satisfaction. Therefore, the hereto paper concentrates on the influence exerted by perceived sacrifice over the business to business customer satisfaction in the insurance industry. More precisely, the objective is to investigate the impact of effort, time and money spent by the business to business customer over satisfaction. The concept of satisfaction has been intensively explored in the literature due to the fact that both practitioners and academics understood that it held a great significance in determining and preserving customer relationships and therefore, long-term profitability. In the service sector, much research has been conducted in the business to consumer context, especially concentrated on the relationship between service quality and satisfaction, whereas the business to business setting received less attention. In order to explore the relationship between perceived sacrifice and satisfaction, a descriptive research design was used. A questionnaire was created using multiple items for measuring satisfaction and perceived sacrifice and also a number of identification variables. The survey concerned companies that had had benefitted from the services of an insurance broker at least once. Copies of the questionnaire were sent by email to company managers from all the main industries. A total of 85 answers were collected. With the help of SPSS tool, the two measurement scales were tested for reliability and validity and a factor analysis was performed. The next step was to calculate the composite scores for each of the two variables and to carry out the simple linear regression analysis. Our linear model considers that

  6. Investigation on the relationship between mental workload and musculoskeletal disorders among nursing staff

    Directory of Open Access Journals (Sweden)

    Yousef Mahmoudifar

    2018-01-01

    Full Text Available Aims: High prevalence of musculoskeletal disorders owing to the work is one of the popular discomforts between nursing staff. High level of workload is considered as a serious problem and identified as a stressor in the nursing. This study intends to recognize the relationship between musculoskeletal disorders and mental workload in nursing personnel reside at southern part of West Azerbaijan province Iran in 2017. Materials and Methods: In this analytical-descriptive study, 100 nurses working in West Azerbaijan hospitals have been randomly selected. Nordic and National Aeronautics and Space Administration-Task Load Index workload questionnaires have been simultaneously utilized as data collection tools. Data analysis has also carried out using SPSS, variance analysis tests, multiple linear regression, and Pearson's correlation coefficient. Results: Results suggest that the most frequent complaints of musculoskeletal problems are associated to the back area. Investigation on sextet scales of mental workload indicates that each of the six scales of workload was at the high-risk level and the average of total workload was 72.45 ± 19.45 which confirms a high-risk level. Pearson's correlation coefficient also indicates mental workload elements have a significant relationship with musculoskeletal disorders (P < 0.05. Conclusion: The results suggest there is a relationship between musculoskeletal disorders and mental workload and the majority of personnel had mental workload with high-risk level. The best way of management planning to mitigate the risk of musculoskeletal disorders arising of mental workload is, therefore, managing-controlling approach such as staff training, job rotation, and time management.

  7. THE INVESTIGATION OF RELATIONSHIP BETWEEN ATTACHMENT AND AGGRESSIVE BEHAVIOR OF ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    Bilge Kaplan

    2013-06-01

    Full Text Available Various studies available in the literature on pubertşy. The individual's physical and psychological changes during puberty, as well as changes in the social field are remarkable. During this period, the importance of family relationships with losing a bit more with the relationships with their peers is their strength. The aim of this study is to investigate the relationship between parental attachment and aggression in adolescents. In the study, risk factors and protective factors between parent attachment and aggressive behavior were examined. Parents marital accord to have friend; close friend and peer group were considered as protective factors. Watching violent movies on Tv and having a disciplinary penalt were identified as risk factors. Also, that empathy was between parent attachment aggression examined as a mediator. That research is carried with randomly selected 1424 (709 females and 715 males adolescents, who are living in Burdur in 2010, going to high school and ranging from 13 and 19. The schools were visited after obtaining necessary permits from the Burdur Directorate Education by the researcher and participation in the study was based on volunteerism. Personal information form, and Aggression Scale (Buss ve Perry, 1992, Parent and Peer Attachment inventory (Armsden ve Greenberg, 1987 and Empathic Tendency Scale (Dökmen, 1988 were applied in the study. For the data analysis, the statistical analysis like Two-way analysis of variance, T-test and Sobel Test were used. When taking a look at analysis findings, it was noticed that adolescents insecurely attached got higher aggression score. It was seen that only the level of emphaty get on with each other between insecure parent attachment and aggression. In the light of literature, the findings of that research were discussed with the other studies’ findings regarding that subject and were interprented. In addition, suggestions relevant to those findings were presented for

  8. Investigating the relationship between work values and work ethics: A South African perspective

    Directory of Open Access Journals (Sweden)

    Petronella Jonck

    2017-02-01

    Full Text Available Orientation: As a result of the proliferation of unethical behaviour in the workplace, the study of work ethics has received new impetus. Research purpose: The research study sought to determine the relationship between work ethics and work values, with the objective of determining whether work ethics statistically significantly predict work values. Motivation for the study: As work ethics (i.e. behavioural intent are a determinant of work values (i.e. overt behaviour, researchers are investigating their potential in preventing unethical behaviour. Research design, approach and method: A descriptive quantitative research design was employed in the study. A survey was conducted using the Multidimensional Work Ethic Profile and the Values Scale, which in previous studies have produced acceptable Cronbach’s alpha coefficients. Data were collected from 301 respondents in one geographical area in South Africa. Main findings: Work values did not appear to be highly esteemed by respondents, as only 6 of the 22 dimensions had a positive score. However, all seven dimensions of work ethics had positive scores. A negative correlation was found between work ethics and work values. In addition, work ethics predicted 9% of the variance in work values, providing sufficient evidence to accept the postulated research hypothesis. Practical implications: The findings of the study could be used by human resource managers to promote ethical behaviour, by focusing not only on work ethics but also on the relationship between work ethics and work values. Contribution: The study provides evidence of a relationship between work ethics and work behaviours, such as work values, within the South African context, and it thus addresses a research gap in this area.

  9. Genetic relationships among Vietnamese local pigs investigated using genome-wide SNP markers.

    Science.gov (United States)

    Ishihara, S; Arakawa, A; Taniguchi, M; Luu, Q M; Pham, D L; Nguyen, B V; Mikawa, S; Kikuchi, K

    2018-02-01

    Vietnam is one of the most important countries for pig domestication, and a total of 26 local breeds have been reported. In the present study, genetic relationships among the various pig breeds were investigated using 90 samples collected from local pigs (15 breeds) in 15 distantly separated, distinct areas of the country and six samples from Landrace pigs in Hanoi as an out-group of a common Western breed. All samples were genotyped using the Illumina Porcine SNP60 v2 Genotyping BeadChip. We used 15 160-15 217 SNPs that showed a high degree of polymorphism in the Vietnamese breeds for identifying genetic relationships among the Vietnamese breeds. Principal components analysis showed that most pigs indigenous to Vietnam formed clusters correlated with their original geographic locations. Some Vietnamese breeds formed a cluster that was genetically related to the Western breed Landrace, suggesting the possibility of crossbreeding. These findings will be useful for the conservation and management of Vietnamese local pig breeds. © 2018 Stichting International Foundation for Animal Genetics.

  10. A longitudinal investigation of the relationship between maternal mind-mindedness and theory of mind.

    Science.gov (United States)

    Kirk, Elizabeth; Pine, Karen; Wheatley, Lisa; Howlett, Neil; Schulz, Joerg; Fletcher, Ben C

    2015-11-01

    Data are presented from a longitudinal investigation examining the relationship between maternal mind-mindedness (MM) in infancy and socio-cognitive development in childhood. We revisited children (n = 18) who had taken part in a longitudinal study as infants. MM had been assessed at 10, 12, 16, and 20 months of age. We followed up these children at 5-6 years of age to test their higher order theory of mind (ToM) (using the strange stories task). The convergent validity, temporal stability, and predictive validity of the construct of MM were examined in a longitudinal data set. The five measures of MM were not significantly correlated. Mother's production of appropriate mind-related comments (but no other measures) showed evidence of temporal stability throughout infancy. Thus, MM (as measured by appropriate mind-related comments) was confirmed as a stable construct. Children's ToM at 5-6 years of age was significantly predicted by their mother's MM up to 4 years earlier, with MM accounting for 40% of the variance of the strange stories task scores. These findings identify a relationship between MM across a protracted period of infancy and socio-cognitive development at 5-6 years of age. © 2015 The British Psychological Society.

  11. Relationship of working mothers' parenting style and consistency to early childhood development: a longitudinal investigation.

    Science.gov (United States)

    Tong, Lian; Shinohara, Ryoji; Sugisawa, Yuka; Tanaka, Emiko; Maruyama, Akiko; Sawada, Yuko; Ishi, Yukiko; Anme, Tokie

    2009-10-01

    This paper is a report of a longitudinal study of the relationship of working mothers' parenting style to their children's social competence and vocabulary/ motor/intellectual development. With an increasing number of women choosing to remain in the workforce after starting a family, there has been a concomitant increase in use of non-parental childcare facilities to help look after the child while the mother is at work. This increase in non-parental care has led to a dramatic change in the traditional child-rearing environment. Long-term investigations were conducted over a period of 2 years in 41 Japanese government-licensed childcare facilities. Child development was evaluated by childcare professionals and parenting style was assessed by questionnaire. A total of 504 children and their mothers participated in the study. Data collection was carried out in 2004 and 2006. We found that the changes in parenting style were statistically significantly related to children's development after 2 years. For instance, changes in the parent-child playing routine contributed to the child's social competence (odds ratio = 11.088). Variation in working mothers' disciplinary practices was also associated with children's vocabulary development after 2 years (odds ratio = 2246). Working mothers should increase interactions with their children in their free time to reduce the risk of developmental delay. Daily childcare support provided by family members or social organizations for long-term working mothers is helpful in mediating the negative relationship of mothers' working with children's development.

  12. Investigating the relationship between media multitasking and processes involved in task-switching.

    Science.gov (United States)

    Alzahabi, Reem; Becker, Mark W; Hambrick, David Z

    2017-11-01

    Although multitasking with media has increased dramatically in recent years (Rideout, Foehr, & Roberts, 2010), the association between media multitasking and cognitive performance is poorly understood. In addition, the literature on the relationship between media multitasking and task-switching, one measure of cognitive control, has produced mixed results (Alzahabi & Becker, 2013; Minear et al., 2013; Ophir, Nass, & Wagner, 2009). Here we use an individual differences approach to investigate the relationship between media multitasking and task-switching performance by first examining the structure of task-switching and identifying the latent factors that contribute to switch costs. Participants performed a series of 3 different task-switching paradigms, each designed to isolate the effects of a specific putative mechanism (e.g., advanced preparation) related to task-switching performance, as well as a series of surveys to measure media multitasking and intelligence. The results suggest that task-switching performance is related to 2 somewhat independent factors, namely an advanced preparation factor and passive decay factor. In addition, multitasking with media was related to a faster ability to prepare for tasks, resulting in faster task-switching performance without a cost to accuracy. Media multitasking and intelligence were both unrelated to passive decay factors. These findings are consistent with a 2-component model of task-switching (Sohn & Anderson, 2001), as well as an automatic/executive framework of cognitive control (Schneider & Shiffrin, 1977). (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Analysis of large brain MRI databases for investigating the relationships between brain, cognitive, and genetic polymorphisms

    International Nuclear Information System (INIS)

    Mazoyer, B.

    2006-01-01

    A major challenge for the years to come is the understanding of the brain-behaviour relationships, and in particular the investigation and quantification of the impact of genetic polymorphism on these relationships. In this framework, a promising experimental approach, which we will refer to as neuro-epidemiologic imaging, consists in acquiring multimodal (brain images, psychometric an d sociological data, genotypes) data in large (several hundreds or thousands ) cohorts of subjects. Processing of such large databases requires on first place the conception and implementation of automated 'pipelines', including image registration, spatial normalisation tissue segmentation, and multivariate statistical analysis. Given the number of images and data to be processed, such pipelines must be both fully automated and robust enough to be able to handle multi-center MRI data, e.g. having inhomogeneous characteristics in terms of resolution and contrast. This approach will be illustrated using two databases collected in aged healthy subjects, searching for the impact of genetic and environmental on two markers of brain aging, namely white matter hyper-signals, and grey matter atrophy. (author)

  14. Dental anxiety and personality: investigating the relationship between dental anxiety and self-consciousness.

    Science.gov (United States)

    Economou, George C

    2003-09-01

    This study investigated whether personality plays a role in a condition called dental anxiety. Specifically, the study examined the relationship between dental anxiety (the negative response to the stress elicited from a dental interaction) and self-consciousness (the tendency to evaluate aspects of oneself that are subject to private and public display). The purpose of this study was to identify the characteristics possessed by dentally anxious individuals who face potential health risks because of their avoidance. Sixty York University undergraduate students were recruited by convenience sampling to participate. These subjects completed Corah's Dental Anxiety Scale and the Self-Consciousness Scale. The Self-Consciousness Scale consists of three subscales, including private self-consciousness, public self-consciousness, and social anxiety. Results indicated an 0.54 significant correlation between dental anxiety and self-consciousness. The public self-consciousness and social anxiety subscales correlated the most with dental anxiety. Furthermore, the data did not indicate a significant moderating relationship for gender between the two aforementioned variables. These results contribute to the establishment of personality characteristics as one of the dimensions determining dental anxiety.

  15. An investigation of relationships among genetic counselors' supervision skills and multicultural counseling competence.

    Science.gov (United States)

    Kyung Lee, Hyun; McCarthy Veach, Patricia; LeRoy, Bonnie S

    2009-06-01

    As racial and ethnic diversity increase in the U.S., genetic counselor multicultural competence is growing in importance. In mental health counseling, supervisor multicultural competence has been shown to promote supervisees' multicultural competence. Moreover, developmentally-advanced supervisors tend to be more effective. This study was designed to investigate relationships among genetic counselor supervisors' perceived multicultural counseling competence and development as supervisors, and their ability to evaluate a supervisee's multicultural skills. One hundred twenty-two supervisors completed an online survey of demographics, the Multicultural Counseling Knowledge and Awareness Scale, the Supervisor Development Scale, and a hypothetical vignette in which they evaluated a supervisee's multicultural skills and provided written feedback. Stepwise multiple regression yielded five significant predictors accounting for 31% of the variance in accuracy of supervisor evaluations of the student: multicultural awareness, multicultural knowledge, age, supervision experience, and supervisor development. Six feedback themes were identified from written responses. Practice and research suggestions are provided.

  16. An empirical investigation of the relationship among forms of workplace mistreatment.

    Science.gov (United States)

    Walsh, Benjamin M; Magley, Vicki J

    2014-01-01

    Organizational researchers argue that workplace mistreatment scholarship is hampered because of the wide variety of constructs studied. To investigate this concern, we conducted an item-level analysis of the relationship among workplace mistreatment experiences to assess construct overlap. Employed students reported how similar 17 mistreatment experiences were to one another (i.e., from measures of sexual harassment, generalized harassment, and incivility) and subject matter experts indicated the degree to which each experience represented several dimensions including Buss's (1961) dimensions (i.e., verbal/physical, active/passive, and direct/indirect) and others (i.e., sexual/ nonsexual and intentional/accidental). Nonsexual forms of mistreatment (i.e., generalized harassment and incivility) were perceived similarly despite their different conceptual definitions, whereas sexual harassment experiences were relatively distinct. Implications of the findings are discussed.

  17. An investigation on the relationship between TQM and ICT in revenue agency organizations

    Directory of Open Access Journals (Sweden)

    Mahmoud Bani

    2014-06-01

    Full Text Available This paper presents an empirical investigation to study the effects of information and communication technology (ICT on total quality management (TQM. The study is applied for a case study of revenue agency in city of Damghan, Iran. The proposed study consists of 33 questions in five categories including leadership and commitment of top management team, customer satisfaction, empowering employees and their partnership, organizational design perspective and quality of information system. Cronbach alpha has been calculated as 0.95, which validates the overall questionnaire. Using Pearson correlation ratio as well as t-student test, the study has determined that there was a positive and meaningful relationship between ICT and TQM components.

  18. Investigating the Relationship between Learning Style Preferences and Teaching Collaboration Skills and Technology

    DEFF Research Database (Denmark)

    Kim, Seung L.; Sonnenwald, Diane H.

    2002-01-01

    This paper reports on an exploratory study that investigates the relationship between participants' learning style preferences and their perceptions of a professional workshop on collaboration and technology to support collaboration. The Learning Preference Scale-Students (LPSS) (Owens & Barnes...... style, and Group 2 showed a strong preference for competitive and cooperative learning styles. Group 1 rated the workshop more positively than Group 2. However, Group 2 reported a larger increase in self-efficacy compared to those in Group 1 (18.9% vs. 6.0%). Both groups provided different suggestions...... regarding the content of the workshop. Group 1 suggested adding more discussions and group exercises, whereas Group 2 suggested adding explicit theory or rules to govern behavior. These findings indicate that learning styles should be considered as a potential variable that influences learning outcomes...

  19. Investigating the role of two types of understanding in relationship well-being: Understanding is more important than knowledge

    OpenAIRE

    Pollmann, M.M.H.; Finkenauer, C.

    2009-01-01

    Understanding is at the heart of intimate relationships. It is unclear, however, whether understanding-partners' subjective feeling that they understand each other-or knowledge-partners' accurate knowledge of each other-is more important for relationship well-being. The present article pits these two types of understanding against each other and investigates their effects on relationship well-being. In a prospective study among 199 newlywed couples, partners' self-reported and perceived under...

  20. Investigation on the relationship among sporadic Na, sporadic E, Field aligned irregularities and neutral winds

    Science.gov (United States)

    Sundararajan, Sridharan; Patra, Amit Kumar; Pant, Tarun; Gurubaran, Subramanian; Raghunath, Karnam

    In the Mesosphere and Lower Thermosphere region (80-100 km), metallic atoms, namely, sodium, potassium, lithium, Iron etc are formed due to ablation of meteors. The lidars based on resonance fluorescence principle has been used to study the vertical distribution of sodium atoms, because of their large abundance than other metals. The profiles of sodium density sometimes show enhancement by a factor of 2 than the normal layer in a narrow altitude region of 2 km and on these occasions, they are called sporadic sodium layer, or briefly Ns. On the other hand, there are observations on sporadic E and radar observations of Field Aligned Irregularities (FAI) associated with these sporadic E. Some investigations have been made to understand the relationship between sporadic E and FAI. Considering that sporadic E is composed of metallic ions and the time of metallic ions are larger compared to other ions, the sodium observations in the same height region would be of significant importance to understand the process involved. Despite a few past observations, no clear picture has emerged due to lack of simultaneous measurements of these parameters. The simultaneous observations of FAI echoes by the Indian MST radar and sodium concentration by the sodium lidar at Gadanki (13.5o N, 79.2o E) are being used to investigate the above mentioned relationship. The Sporadic E and neutral wind information are obtained from the ionosonde, meteor/MF radar observations from Trivandrum (8.5o N, 77E) and Tirunelveli (8.7o N, 77.8o E). The results obtained will be presented during the meeting.

  1. The investigation on the relationship between the problem of long-term loan and economic growth

    Institute of Scientific and Technical Information of China (English)

    Wenjie Du

    2011-01-01

    Purpose-Since the reform and opening-up policy,the long-term problem of loans became more and more serious when China's economy maintained rapid growth.The purpose of this paper is to explore the profound causes of the medium-and long-term problem of loans and the relationship between it and economic growth.Design/methodology/approach-Using panel data for 28 provinces and cities of China during 1994-2005,this paper investigates the determinants on the maturity of bank credit using threshold panel data of Hansen.In addition,using dynamics panel data,this paper investigates the effects of the maturity structure of bank credit on economic growth.Findings-The drop of bank industry concentration tends to increase the supply of long-term loans.The raise of economic growth and the increase of industrialization degree promote the demand of long-term loans,significantly.Furthermore,the threshold effects of inflation exist.When the initial inflation is lower than 3.9 percent,the raise of inflation can increase the supply of long-term loans.When the initial inflation is higher than 3.9 percent,the raise of inflation can decrease the supply of long-term loans.The increase in the supply of long-term loans can promote the economic growth.Originality/value-The paper has two innovations:first,when studying the determinants on the maturity of bank credit,using the threshold panel approach takes account of the nonlinear adjustment of inflation;second,including the maturity of bank credit into the realm of financial development studies the relationship between this and economic growth.

  2. Investigating Relationships between and within Entry Pathways on a Sport Related Programme and the Degree Outcome Obtained

    Science.gov (United States)

    Huntley, Tabo; Whitehead, Amy; Cullinane, Danny; Nixon, Sarah; Huntley, Emma

    2017-01-01

    Research within Higher Education in the United Kingdom has reported conflicting findings when investigating the relationship between undergraduate entry routes and gender, with successful performances across the degree cycle. This paper adds to this body of knowledge and examines the relationship between entry routes and gender on student outcomes…

  3. Experimental Investigation and FE Analysis on Constitutive Relationship of High Strength Aluminum Alloy under Cyclic Loading

    Directory of Open Access Journals (Sweden)

    Yuanqing Wang

    2016-01-01

    Full Text Available Experiments of 17 high strength aluminum alloy (7A04 specimens were conducted to investigate the constitutive relationship under cyclic loading. The monotonic behavior and hysteretic behavior were focused on and the fracture surface was observed by scanning electron microscope (SEM to investigate the microfailure modes. Based on Ramberg-Osgood model, stress-strain skeleton curves under cyclic loading were fitted. Parameters of combined hardening model including isotropic hardening and kinematic hardening were calibrated from test data according to Chaboche model. The cyclic tests were simulated in finite element software ABAQUS. The test results show that 7A04 aluminum alloy has obvious nonlinearity and ultra-high strength which is over 600 MPa, however, with relatively poor ductility. In the cyclic loading tests, 7A04 aluminum alloy showed cyclic hardening behavior and when the compressive strain was larger than 1%, the stiffness degradation and strength degradation occurred. The simulated curves derived by FE model fitted well with experimental curves which indicates that the parameters of this combined model can be used in accurate calculation of 7A04 high strength aluminum structures under cyclic loading.

  4. Investigating the relationship between jobs-housing balance and traffic safety.

    Science.gov (United States)

    Xu, Chengcheng; Li, Haojie; Zhao, Jingya; Chen, Jun; Wang, Wei

    2017-10-01

    This study aimed to investigate the effects of jobs-housing balance on traffic safety. The crash, demographic characteristics, employment, road network, household characteristics and traffic data were collected from the Los Angeles in 2010. One-way ANOVA tests indicated that the jobs-housing ratio significantly affects traffic safety in terms of crash frequency at traffic analysis zone (TAZ). To quantify the safety impacts of jobs-housing balance, the semi-parametric geographically weighted Poisson regression (S-GWPR) was further used to link crash frequency at TAZ with jobs-housing ratio and other contributing factors. The S-GWPR provides better fitness to the data than do the generalized linear regression, as the S-GWPR accounts for the spatial heterogeneity. The S-GWPR results showed that the jobs-housing relationship has a significant association with crash frequency at TAZ when the factors of traffic, network, and household characteristics are controlled. Crash frequency at TAZ level increases with an increase in the jobs-housing ratio. To further investigate the interactive effects between jobs-housing ratio and other factors, a comparative analysis was conducted to compare the variable elasticities under different jobs-housing ratios. The results indicate considerable interactive effects that traffic conditions and road network characteristics have different effects on crash frequency under various jobs-housing ratios. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Measuring perceived exercise capability and investigating its relationship with childhood obesity: a feasibility study.

    Science.gov (United States)

    Taylor, M J; Arriscado, D; Vlaev, I; Taylor, D; Gately, P; Darzi, A

    2016-01-01

    According to the COM-B ('Capability', 'Opportunity', 'Motivation' and 'Behaviour') model of behaviour, three factors are essential for behaviour to occur: capability, opportunity and motivation. Obese children are less likely to feel capable of exercising. The implementation of a new methodological approach to investigate the relationship between perceived exercise capability (PEC) and childhood obesity was conducted, which involved creating a new instrument, and demonstrating how it can be used to measure obesity intervention outcomes. A questionnaire aiming to measure perceived exercise capability, opportunity and motivation was systematically constructed using the COM-B model and administered to 71 obese children (aged 9-17 years (12.24±0.2.01), body mass index (BMI) standard deviation scores (SDS) 2.80±0.660) at a weight-management camp in northern England. Scale validity and reliability was assessed. Relationships between PEC, as measured by the questionnaire, and BMI SDS were investigated for the children at the weight-management camp, and for 45 Spanish schoolchildren (aged 9-13 years, (10.52±1.23), BMI SDS 0.80±0.99). A pilot study, demonstrating how the questionnaire can be used to measure the effectiveness of an intervention aiming to bring about improved PEC for weight-management camp attendees, was conducted. No participants withdrew from these studies. The questionnaire domain (exercise capability, opportunity and motivation) composite scales were found to have adequate internal consistency (a=0.712-0.796) and construct validity (χ(2)/degrees of freedom=1.55, root mean square error of approximation=0.072, comparative fit index=0.92). Linear regression revealed that low PEC was associated with higher baseline BMI SDS for both UK (b=-0.289, P=0.010) and Spanish (b=-0.446, P=0.047) participants. Pilot study findings provide preliminary evidence for PEC improvements through intervention being achievable, and measurable using the questionnaire

  6. Investigating the relationship between socially-assigned ethnicity, racial discrimination and health advantage in New Zealand.

    Science.gov (United States)

    Cormack, Donna M; Harris, Ricci B; Stanley, James

    2013-01-01

    While evidence of the contribution of racial discrimination to ethnic health disparities has increased significantly, there has been less research examining relationships between ascribed racial/ethnic categories and health. It has been hypothesized that in racially-stratified societies being assigned as belonging to the dominant racial/ethnic group may be associated with health advantage. This study aimed to investigate associations between socially-assigned ethnicity, self-identified ethnicity, and health, and to consider the role of self-reported experience of racial discrimination in any relationships between socially-assigned ethnicity and health. The study used data from the 2006/07 New Zealand Health Survey (n = 12,488), a nationally representative cross-sectional survey of adults 15 years and over. Racial discrimination was measured as reported individual-level experiences across five domains. Health outcome measures examined were self-reported general health and psychological distress. The study identified varying levels of agreement between participants' self-identified and socially-assigned ethnicities. Individuals who reported both self-identifying and being socially-assigned as always belonging to the dominant European grouping tended to have more socioeconomic advantage and experience less racial discrimination. This group also had the highest odds of reporting optimal self-rated health and lower mean levels of psychological distress. These differences were attenuated in models adjusting for socioeconomic measures and individual-level racial discrimination. The results suggest health advantage accrues to individuals who self-identify and are socially-assigned as belonging to the dominant European ethnic grouping in New Zealand, operating in part through socioeconomic advantage and lower exposure to individual-level racial discrimination. This is consistent with the broader evidence of the negative impacts of racism on health and ethnic inequalities

  7. Investigating the Partial Relationships Between Testability and the Dynamic Range-to-Domain Ratio

    Directory of Open Access Journals (Sweden)

    Zuhoor Al-Khanjari

    2003-11-01

    Full Text Available The word ‘testability’ has been used variously in the software community to represent a number of different concepts such as how easy it is to test a program or how easy it is to achieve execution coverage of certain program components. Voas and colleagues have used the word to capture a slightly different notion, namely the ease with which faults, if present in a program, can be revealed by the testing process. The significance of this concept is twofold. First, if it is possible to measure or estimate testability, it can guide the tester in deciding where to focus the testing effort. Secondly, knowledge about what makes some programs more testable than others can guide the developer so that design-for-test features are built in to the software. The propagation, infection and execution (PIE analysis technique has been proposed as a way of estimating the Voas notion of testability. Unfortunately, estimating testability via the PIE technique is a difficult and costly process. However, Voas has suggested a link with the metric, domain-to-range ratio (DRR. This paper reviews the various testability concepts and summarises the PIE technique. A prototype tool developed by the authors to automate part of the PIE analysis is described and a method is proposed for dynamically determining the inverse of the domain-to-range ratio. This inverse ratio can be considered more natural in some sense and the idea of calculating its value from program execution leads to the possibility of automating its determination. Some experiments have been performed to investigate empirically whether there is a partial link between testability and this dynamic range-to-domain ratio (DRDR. Statistical tests have shown that for some programs and computational functions there is a strong relationship, but for others the relationship is weak.

  8. Investigating the Relationship between Learning Styles and ESP Reading Strategies in Academic Setting

    Directory of Open Access Journals (Sweden)

    Parviz Ajideh

    2018-05-01

    Full Text Available The present study investigated the relationship between Art and Science students’ learning styles and their ESP reading strategies in academic settings. Learning styles are defined as general orientations learners take toward their learning experiences. This notion has recently obtained attention in the area of language learning. Strategies are also defined as specific behaviours or techniques learners employ towards leaning in order to achieve their learning goals. The strategies chosen are often linked to the individual's learning style. The purpose of this study was to identify Art and Science students’ major learning style preferences and their strategies they employ to tackle their reading materials in ESP courses at Tabriz Islamic Art University. To this end, 313 Art and Science students at Tabriz Islamic Art University answered two self-report questionnaires (PLSPQ and SORS to identify their major and minor learning styles as well as their reading strategies in ESP reading. In order to find any relationship between the students’ preferred learning style (s and their reading strategies in ESP, Pearson Product Moment Coefficient r was used to analyze the participants’ answers to the questionnaires. The results showed that Art students favored Kinesthetic, Auditory, Visual and Tactile learning styles as their major learning styles while Science students showed preference to only Kinesthetic Learning style as their major learning style and other learning styles as their minor ones. It was also found that the most dominant reading strategies both Art and Science students apply in reading their ESP texts was cognitive strategies. Correlational analyses of their major learning styles and their reading strategies are discussed.

  9. Investigating genotype-phenotype relationships in Rett syndrome using an international data set.

    Science.gov (United States)

    Bebbington, A; Anderson, A; Ravine, D; Fyfe, S; Pineda, M; de Klerk, N; Ben-Zeev, B; Yatawara, N; Percy, A; Kaufmann, W E; Leonard, H

    2008-03-11

    Rett syndrome is an uncommon neurodevelopmental disorder with an incidence of 1:9,000 live female births. The principal genetic cause was first reported in 1999 when the association with mutations in the methyl-CpG-binding protein 2 (or MECP2) gene was identified. This study uses data from a large international database, InterRett, to examine genotype-phenotype relationships and compares these with previous findings in a population-based cohort. The data set for these analyses was derived from a subset of InterRett cases with subject information collected from the family, the clinician, or both. Individual phenotypic characteristics and clinical severity using three scales were compared among those with eight known recurrent pathogenic MECP2 mutations as well as those with C-terminal deletions (n = 272). Overall, p.R270X and p.R255X were the most severe and p.R133C and p.R294X were the mildest mutations. Significant differences by mutation were seen for individual phenotypic characteristics such as hand use, ambulation, and language. This multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations. Although the modifying influence of X inactivation on clinical severity could not be included in the analysis, the findings confirm clear genotype-phenotype relationships in Rett syndrome and show the benefits of collaboration crucial to effective research in rare disorders.

  10. Investigation of the relationship between students' problem solving and conceptual understanding of electricity

    Science.gov (United States)

    Cobanoglu Aktan, Derya

    The purpose of this study was to investigate the relationship between students' qualitative problem solving and conceptual understanding of electricity. For the analysis data were collected from observations of group problem solving, from their homework artifacts, and from semi-structured interviews. The data for six undergraduate students were analyzed by qualitative research methods. The students in the study were found to use tools (such as computer simulations and formulas) differently from one another, and they made different levels of interpretations for the electricity representations. Consequently each student had different problem solving strategies. The students exhibited a wide range of levels of understanding of the electricity concepts. It was found that students' conceptual understandings and their problem solving strategies were closely linked with one another. The students who tended to use multiple tools to make high level interpretations for representations to arrive at a single solution exhibited a higher level of understanding than the students who tended to use tools to make low level interpretations to reach a solution. This study demonstrates a relationship between conceptual understanding and problem solving strategies. Similar to the results of the existing research on students' quantitative problem solving, it was found that students were able to give correct answers to some problems without fully understanding the concepts behind the problem. However, some problems required a conceptual understanding in order for a student to arrive at a correct answer. An implication of this study is that careful selection of qualitative questions is necessary for capturing high levels of conceptual understanding. Additionally, conceptual understanding among some types of problem solvers can be improved by activities or tasks that can help them reflect on their problem solving strategies and the tools they use.

  11. Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

    Directory of Open Access Journals (Sweden)

    Saba Garshasbi

    2015-10-01

    Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

  12. PRELIMINARY INVESTIGATIONS ON RELATIONSHIP BETWEEN POLYMORPHISM AT CAST LOCUS AND THE QUALITY OF PORK

    Directory of Open Access Journals (Sweden)

    Ivona Đurkin

    2009-12-01

    Full Text Available The present study was performed in order to investigate a relationship between polymorphisms on the calpastatin gene (CAST and pig meat quality traits. The investigation was carried out on 29 gilts and barrows, crosses of Large White x German Landrace randomly selected at slaughter line. Pigs were slaughtered at 130-150 kg of live weight and blood samples were taken for genomic DNA analysis. The following indicators of meat quality and meat chemical composition were evaluated: pH and electric conductivity measured 45 minutes post mortem in m. Longissimus dorsi (LD muscle and in M. Semimembranosus (SM muscle; electric conductivity measured at the same locations after 24h of cooling; drip loss (determined by “bag method”; colour (measured with Minolta chromameter and expressed as Hunter L, a, b values; instrumental tenderness assessed as Warner-Bratzler (WB shear force and moisture, fat, protein and collagen content (% determined on cooked LD muscle after 24h of thawing. The amplification products of the CAST gene were digested with HinfI restriction endonuclease and three genotypes (AA, BB and AB were revealed. Statistical analysis showed that meat originated from pigs of AB genotype had the lowest WB shear force and the highest protein content of cooked LD muscle. As for the indicators of technological meat quality, statistically significant differences (p<0.05 were found between genotype AA and both BB and AB genotype for electric conductivity measured in LD muscle after 24h of cooling, as well as between BB and both AA and AB genotypes for drip loss.

  13. A look into the relationship between personality traits and basic values: A longitudinal investigation.

    Science.gov (United States)

    Vecchione, Michele; Alessandri, Guido; Roccas, Sonia; Caprara, Gian Vittorio

    2018-05-27

    The present study examines the longitudinal association between basic personal values and the Big Five personality traits. A sample of 546 young adults (57% females) with a mean age of 21.68 years (SD = 1.60) completed the Portrait Values Questionnaire and the Big Five Questionnaire at three-time points, each separated by an interval of four years. Cross-lagged models were used to investigate the possible reciprocal relations between traits and values, after the stability of the variables was taken into account. We found that values did not affect trait development. Traits, by contrast, have some effects on how values change. Specifically, high levels of agreeableness predict an increase over time in the importance assigned to benevolence values. Similarly, high levels of openness predict a later increase in the importance assigned to self-direction values. The same effect was not found for the other traits. Additionally, except for in the case of emotional stability, traits showed synchronous (i.e., within wave) correlations with values, suggesting that part of this relationship is due to common antecedents. Mechanisms underlying the associations between traits and values are discussed. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  14. Investigation of relationship between workaholism and obsession in public and private sector workers

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    Ali Emhan

    2012-03-01

    Full Text Available Objectives: In this study, the relationship between levels of workaholism and obsession was investigated in a group that was composed of independent accountantfinancial advisers and civil servants.Materials and methods: Two different scales were used in order to determine the workaholism and obsession levels. These two scales and a form to collect demographical variables were administered to 260 workers. Among them the data obtained from 170 workers were evaluated. Parametric tests and correlation analysis were used to analyze the data. The level of statistical significance was accepted as p<0.05.Results: The work enjoyment (WE scores of independent accountant-financial advisers were higher than those of both civil servants and their employee. WE scores of participants who have graduated from university degree were higher than those of students who were high school graduates. There were positive correlations between WE score of workaholism scale and control and just-right scores. Additionally, work driven score of workaholism scale was found to be positively correlated with cleaning, ruminations, and control and just-right scores.Conclusion: It can be said that there is a positive correlation between workaholism sub components and obsessions.

  15. Investigation of the relationship between earthquakes and indoor radon concentrations at a building in Gyeongju, Korea

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    Jae Wook Kim

    2018-04-01

    Full Text Available This article measured and analyzed the indoor radon concentrations at one university building in Gyeongju, Republic of Korea, to investigate if there is any relationship between earthquakes and indoor radon concentration. Since 12 September 2016, when two 5.1 and 5.8 magnitude earthquakes occurred, hundreds of aftershocks affected Gyeongju until January 2017. The measurements were made at the ground floor of the Energy Engineering Hall of Dongguk University in Gyeongju over a period between February 2016 and January 2017. The measurements were made with an RAD7 detector on the basis of the US Environmental Protection Agency measurement protocol. Each measurement was continuously made every 30 minutes over the measurement period every month. Among earthquakes with 2.0 or greater magnitude, the earthquakes whose occurrence timings fell into the measurement periods were screened for further analysis. We observed similar spike-like patterns between the indoor radon concentration distributions and earthquakes: a sudden increase in the peak indoor radon concentration 1–4 days before an earthquake, gradual decrease before the earthquake, and sudden drop on the day of the earthquake if the interval between successive earthquakes was moderately longer, for example, 3 days in this article. Keywords: Earthquakes, Gyeongju, Indoor Radon Concentration, RAD7, Radon Anomaly

  16. Prenatal irradiation and spatial memory in mice: investigation of dose-response relationship

    International Nuclear Information System (INIS)

    Sienkiewicz, Z.J.; Haylock, R.G.E.; Saunders, R.D.

    1994-01-01

    Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable. (Author)

  17. Investigation Clinical Competence and Its Relationship with Professional Ethics and Spiritual Health in Nurses

    Directory of Open Access Journals (Sweden)

    Elahe Ramezanzade Tabriz

    2017-03-01

    Full Text Available Abstract Background and Objectives: Study of clinical competence in nursing helps determine the quality of health care delivered to patients. Given the priority of observance of principles over caretaking and necessity of spirituality existence at the core of health care provision, this study was conducted to investigate clinical competence and its relationship with professional ethics and spiritual health in nurses. Methods: In this cross-sectional, descriptive, and correlational study, 281 nurses were enrolled by consensus sampling. Sampling was conducted from February, 2016 till June, 2016. The data were gathered by a demographics questionnaire, a self-assessment scale of clinical competence, a nursing ethics questionnaire, and a spiritual health questionnaire, and analyzed by descriptive statistics and t-test, Pearson's correlation coefficient, ANOVA, and linear regression analysis in SPSS 21. Results: The total scores for self-assessment scale of nurses' clinical competence, professional ethics, and spiritual health were moderate. In the light of the results of Spearman's correlation coefficient, there was a significant and positive correlation between clinical competence and spiritual health. Moreover, a significant positive correlation was observed between professional ethics and spiritual health but there was no correlation between professional ethics and clinical competence. Conclusion: Managers' and personnel's Knowledge about the level of nurses clinical competence, professional ethics, and spiritual health in teaching health care centers provides valuable information to develop in-service and efficacious education programs and ultimately to improve the quality of nursing services.

  18. Investigating the prevalence of personality disorders and its relationship with personality traits among students

    Directory of Open Access Journals (Sweden)

    Davod Ghaderi

    2016-04-01

    Full Text Available The present study was aimed to investigate the prevalence of personality disorders and its relationship with personality traits among students. This research was among epidemiological-correlational descriptive studies. Method: For this purpose, 389 male students were selected via a multi-stage cluster sampling method. All subjects completed Millon's personality disorder (1987 and five-factor personality Costaand McCrae's questionnaires (1989. Results: The results showed that the prevalence of personality disorders is among students. It was also found that there existed a positive correlation between schizoid, avoidant, dependent, schizotypal, borderline and paranoid personality disorders with Neuroticism factor (r = .1. There was a significant negative correlation between schizoid, avoidant and schizotypal personality disorders with extraversion factor (r = .1 and significant positive correlation between histrionic disorders and extraversion (r = .1. There was a significant negative correlation between dependent personality disorder and Openness factor (r = .1 , significant negative correlation between narcissistic, antisocial and paranoid personality disorders with agree ableness factor (r = .1 and finally, significant negative correlation between antisocial, passive-aggressive and borderline personality disorders with accountability factor (r = .1and a significant positive correlation between accountability factor and compulsive personality disorder (r = .1. Conclusion: The results suggest a prevalence of personality disorders among students and significant correlation between some disorders with personality factors. Further studies in this area could provide more insightful findings in the field.

  19. Combining Empirical Relationships with Data Based Mechanistic Modeling to Inform Solute Tracer Investigations across Stream Orders

    Science.gov (United States)

    Herrington, C.; Gonzalez-Pinzon, R.; Covino, T. P.; Mortensen, J.

    2015-12-01

    Solute transport studies in streams and rivers often begin with the introduction of conservative and reactive tracers into the water column. Information on the transport of these substances is then captured within tracer breakthrough curves (BTCs) and used to estimate, for instance, travel times and dissolved nutrient and carbon dynamics. Traditionally, these investigations have been limited to systems with small discharges (turbidity (e.g., nitrate signals with SUNA instruments or fluorescence measures) and/or high total dissolved solids (e.g., making prohibitively expensive the use of salt tracers such as NaCl) in larger systems. Additionally, a successful time-of-travel study is valuable for only a single discharge and river stage. We have developed a method to predict tracer BTCs to inform sampling frequencies at small and large stream orders using empirical relationships developed from multiple tracer injections spanning several orders of magnitude in discharge and reach length. This method was successfully tested in 1st to 8th order systems along the Middle Rio Grande River Basin in New Mexico, USA.

  20. The relationship between senior management team culture and clinical governance: Empirical investigation and managerial implications.

    Science.gov (United States)

    Prenestini, Anna; Calciolari, Stefano; Lega, Federico; Grilli, Roberto

    2015-01-01

    Health care organizations are pressured to improve the cost-effectiveness of service delivery. Clinical governance is an important trigger to improve care quality and safety and rank high in the reform agenda of health systems. The senior management team culture plays a major role in establishing clinical governance practices, because it strongly influences the values, attitudes, and behaviors of the members of an organization. The aim of this study was to investigate the relationship between senior management team culture and clinical governance in the public health care organizations of three Italian regions. The assessment of senior management culture was conducted using the Competing Values Framework and a corresponding instrument adapted for the Italian context. Clinical governance was assessed using an ad hoc instrument focused on the senior management team's perception and attitude toward clinical governance. The survey achieved a 54% response rate. The results of four different models demonstrate that organizations characterized by different dominant cultures are associated with significant differences in attitudes toward clinical governance. In particular, on average, dominant cultures with a prevailing external focus are associated with a more positive attitude toward clinical governance. The selection and appointments of top managers should consider the style of leadership that is most apt to facilitate the growth of rational and developmental cultures. Furthermore, the training of top managers and leading doctors should reinforce leadership aptitude and approaches that are consistent with the desired organizational cultures.

  1. Investigating the Relationship among Test Anxiety, Gender, Academic Achievement and Years of Study: A Case of Iranian EFL University Students

    Science.gov (United States)

    Rezazadeh, Mohsen; Tavakoli, Mansoor

    2009-01-01

    The construct of anxiety plays a major role in one's life. One of these anxieties is test anxiety or apprehension over academic evaluation. The present study was designed to investigate the relationship between gender, academic achievement, years of study and levels of test anxiety. This investigation is a descriptive analytic study and was done…

  2. Investigation of Relationship between Organizational Climate and Organizational Citizenship Behavior: A Research on Health Sector

    OpenAIRE

    Serdar Öge; Pınar Erdogan

    2015-01-01

    The main objective of this research is to describe the relationship between organizational climate and organizational citizenship behavior. In order to examine this relationship, a research is intended to be carried out in relevant institutions and organizations operating in the health sector in Turkey. It will be researched that whether there is a statistically significant relationship between organizational climate and organizational citizenship behavior through elated ...

  3. Investigating the relationship between socially-assigned ethnicity, racial discrimination and health advantage in New Zealand.

    Directory of Open Access Journals (Sweden)

    Donna M Cormack

    Full Text Available BACKGROUND: While evidence of the contribution of racial discrimination to ethnic health disparities has increased significantly, there has been less research examining relationships between ascribed racial/ethnic categories and health. It has been hypothesized that in racially-stratified societies being assigned as belonging to the dominant racial/ethnic group may be associated with health advantage. This study aimed to investigate associations between socially-assigned ethnicity, self-identified ethnicity, and health, and to consider the role of self-reported experience of racial discrimination in any relationships between socially-assigned ethnicity and health. METHODS: The study used data from the 2006/07 New Zealand Health Survey (n = 12,488, a nationally representative cross-sectional survey of adults 15 years and over. Racial discrimination was measured as reported individual-level experiences across five domains. Health outcome measures examined were self-reported general health and psychological distress. RESULTS: The study identified varying levels of agreement between participants' self-identified and socially-assigned ethnicities. Individuals who reported both self-identifying and being socially-assigned as always belonging to the dominant European grouping tended to have more socioeconomic advantage and experience less racial discrimination. This group also had the highest odds of reporting optimal self-rated health and lower mean levels of psychological distress. These differences were attenuated in models adjusting for socioeconomic measures and individual-level racial discrimination. CONCLUSIONS: The results suggest health advantage accrues to individuals who self-identify and are socially-assigned as belonging to the dominant European ethnic grouping in New Zealand, operating in part through socioeconomic advantage and lower exposure to individual-level racial discrimination. This is consistent with the broader evidence of the

  4. Investigation of the relationship between convenient visits and doctors' fatigue using burnout and work engagement scales.

    Science.gov (United States)

    Matsumoto, Yuuki; Hoshiko, Michiko; Morimatsu, Yoshitaka; Mori, Mihoko; Kushino, Nanae; Ishitake, Tatsuya

    2015-01-01

    Fatigue caused by high workload is often responsible for the high attrition among doctors, and has contributed to a disruption in community medicine. In order to address this problem, institutional mechanisms at the hospital level are required. Previous studies have shown that systemic measures at the hospital level and a change in the mindset of patients can help manage the problem. "Convenient visits" refer to emergency visits for non-emergency problems. It is an avoidable cause of high workload on doctors. Convenient visits also refer to emergency consultation for non-emergency symptoms. As this is a new phenomenon, its relationship with doctors' fatigue needs further research. We investigated the relationship between convenient visits and doctors' fatigue using burnout and work engagement scales. We selected 44 hospitals, with >200 beds each, in provincial cities of prefectures with a doctor-population ratio lower than the national average. These cities were considered likely to manifest the phenomenon of 24-hour society and include overworked doctors. Ordinance-designated cities were excluded from this study owing to wide population variability. Three doctors from each hospital were randomly selected from among physicians, surgeons, and pediatricians. We distributed questionnaires (a questionnaire concerning convenient visits, Maslach Burnout Inventory-Human Services Survey, and Utrecht Work Engagement Scale) to 132 doctors. Forty-two doctors responded to the survey. The median proportion of convenient visits among emergency visits was 50%. Sixty percent of the doctors surveyed were annoyed by convenient visits. Other doctors indicated good collaboration between the hospitals and communities or that they were not currently annoyed by convenient visits, although they had been annoyed previously. The emotional exhaustion in doctors, who worked in hospitals that did not restrict convenient visits, was significantly higher than in those who worked in hospitals

  5. An Investigation of Relationships between Internal and External Factors Affecting Technology Integration in Classrooms

    Science.gov (United States)

    Hur, Jung Won; Shannon, David; Wolf, Sara

    2016-01-01

    Various factors affecting technology integration have been identified, but little research has examined the relationships between factors, especially internal and external ones, and whether they directly or indirectly influenced each other. To fill this research gap, this study examined the significance and relationships of five factors…

  6. Investigation on the relationship between systemic burden and annual limits on intake of radionuclides

    International Nuclear Information System (INIS)

    Zhou Yongzeng

    1984-01-01

    The concept of systemic burden and the calculation of annual limits on intake (ALI) of radionuclides are discussed. The relationship between these two quantities is also described. Using this relationship, the ratio of actual amount of intake to ALI can be obtained for the assessment of the risk to internal exposure

  7. A Qualitative Investigation of College Students' Facebook Usage and Romantic Relationships: Implications for College Counselors

    Science.gov (United States)

    Sherrell, Renee S.; Lambie, Glenn W.

    2016-01-01

    The use of social media is a societal trend influencing the way that individuals communicate with and relate to one another. Moreover, Facebook use may facilitate or hinder individuals' relationship growth and development. The purpose of this article is to (a) review research examining Facebook usage and interpersonal relationships, (b) present…

  8. Investigating the Dynamics of Formative Assessment: Relationships between Teacher Knowledge, Assessment Practice and Learning

    Science.gov (United States)

    Herman, Joan; Osmundson, Ellen; Dai, Yunyun; Ringstaff, Cathy; Timms, Michael

    2015-01-01

    This exploratory study of elementary school science examines questions central to policy, practice and research on formative assessment: What is the quality of teachers' content-pedagogical and assessment knowledge? What is the relationship between teacher knowledge and assessment practice? What is the relationship between teacher knowledge,…

  9. Investigating the brand love-brand hate relationship, and the effects of brand attitude and brand attachment on brand hate

    OpenAIRE

    Silden, Sandra Emilie; Skeie, Malin Elida

    2015-01-01

    There has been an increase in consumer research on consumer-brand relationships, specifically positive relationship between the consumer and brands. This thesis tries to shed light on a topic that has received less attention, though highly related, namely brand hate. Study 1 was conducted in order to investigate an antecedent to brand hate, building on the fact that love for a competing brand can cause brand hate. To our knowledge this topic has not been examined before. However, a line of re...

  10. Investigating the Relationship between Family Emotional Atmosphere and Affective Control with Tendency to Addiction

    Directory of Open Access Journals (Sweden)

    سالار عبدالملکی

    2017-03-01

    Full Text Available The present study examined the relationship between family emotional atmosphere and affective control with tendency to drug abuse. The study population included all 7500 residents of Qaleh town from Qorveh city. By simple random sampling 323 individuals included the sample group of this study. Family Emotional Atmosphere Questionnaire (FEAQ, Affective Control Scale (ACS, and Tendency to Addiction Questionnaire were the measurement tools for this study. The results indicated that there were significant relationships between family emotional atmosphere with tendency to addiction and its subscales. Also, there was a significant relationship between affective control and tendency to addiction. There is significant relationship between tendency to addiction with all subscales of affective control except anger subscale. In conclusion, there is relationship between family emotional atmosphere and affective control with tendency to addiction. Also, family emotional atmosphere can predict tendency to addiction; while, affective control cannot.

  11. Buffering effect of positive parent-child relationships on adolescent risk taking: A longitudinal neuroimaging investigation

    Science.gov (United States)

    Qu, Yang; Fuligni, Andrew J.; Galvan, Adriana; Telzer, Eva H.

    2015-01-01

    Adolescence is marked by a steep increase in risk-taking behavior. The serious consequences of such heightened risk taking raise the importance of identifying protective factors. Despite its dynamic change during adolescence, family relationships remain a key source of influence for teenagers. Using a longitudinal fMRI approach, we scanned 23 adolescents twice across a 1.5-year period to examine how changes in parent-child relationships contribute to changes in adolescent risk taking over time via changes in adolescents’ neural reactivity to rewards. Results indicate that although parent-child relationships are not associated with adolescent risk taking concurrently, increases in positive parent-child relationships contribute to declines in adolescent risk taking. This process is mediated by longitudinal decreases in ventral striatum activation to rewards during risk taking. Findings highlight the neural pathways through which improvements in positive parent-child relationships serve to buffer longitudinal increases in adolescent risk taking. PMID:26342184

  12. Investigating of Relationship between Conflict and Trust on the Golestan Province Red Crescent Society Volunteer Groups

    Directory of Open Access Journals (Sweden)

    Seidmehdi Mehdi Veiseh

    2014-06-01

    Full Text Available Conflict is the most important behavioral issues that, in several last deceed organizational behavior scholars intentioned to it .according to several idea about positive effects of management of conflict in organization relationship between conflict and many variables had been surveyed .in this research relationship between conflict and trust was surveyed. According to this, researchers studied the theatrical basic of research correctly and recognized main component s and variables by descriptive-survey method in this research and selected sample by random sampling and surveyed research assumptions in Golestan Red Crescent organization. Results of research shows that task conflict related with intergroup trust directly, also there is any relationship between relationship conflict and trust. Finally task conflict related with relationship conflict directly

  13. Investigation of relationship between mental workload and information flow rate of accident diagnosis tasks in NPPs

    International Nuclear Information System (INIS)

    Ha, Chang Hoon

    2005-02-01

    The objective of this study is to investigate experimentally the relationship between an operator's mental workload and the information flow rate of accident diagnosis tasks and further to propose the information flow rate as an analytic method for measuring the mental workload. There are two types of mental workload in the advanced MCR of NPPs: the information processing workload, which is the processing that the human operator must actually perform in order to complete the diagnosis task, and emotional stress workload experienced by the operator. In this study, the focus is on the former. Three kinds of methods are used to measure the operator's workload: information flow rate, subjective methods, and physiological measures. Information flows for eight accident diagnosis tasks are modeled qualitatively using a stage model and are quantified using Conant's model. The eight accident cases are considered here are: Loss Of Coolant Accident (LOCA), Steam Generator Tube Rupture (SGTR), Steam Line Break (SLB), Feedwater Line Break (FLB), Pressurizer (PZR) spray and heater failure, Reactor Coolant Pump (RCP) trip, Main Steam Isolation Valve (MSIV) failure, and PZR spray failure. The information flow rate is obtained for each diagnosis task by imposing time limit restrictions for the tasks. Subjective methods require the operators to respond to questionnaires to rate their level of mental effort. NASA-TLX and MCH scale are selected as subjective methods. NASA-TLX is a subjective method used in the various fields including the aviation, automobile, and nuclear industries. It has a multi-dimensional rating technique and provides an overall workload score based on a weighted average on six subscales using pair-wise comparison tests. MCH, on the other hand, is one-dimensional and uses a 10- point rating technique. As with NASA-TLX, the higher the score is, the higher the subjective workload is. For the physiological measurements, an eye tracking system analyzes eye movements

  14. Investigation of relationship between mental workload and information flow rate of accident diagnosis tasks in NPPs

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Chang Hoon

    2005-02-15

    The objective of this study is to investigate experimentally the relationship between an operator's mental workload and the information flow rate of accident diagnosis tasks and further to propose the information flow rate as an analytic method for measuring the mental workload. There are two types of mental workload in the advanced MCR of NPPs: the information processing workload, which is the processing that the human operator must actually perform in order to complete the diagnosis task, and emotional stress workload experienced by the operator. In this study, the focus is on the former. Three kinds of methods are used to measure the operator's workload: information flow rate, subjective methods, and physiological measures. Information flows for eight accident diagnosis tasks are modeled qualitatively using a stage model and are quantified using Conant's model. The eight accident cases are considered here are: Loss Of Coolant Accident (LOCA), Steam Generator Tube Rupture (SGTR), Steam Line Break (SLB), Feedwater Line Break (FLB), Pressurizer (PZR) spray and heater failure, Reactor Coolant Pump (RCP) trip, Main Steam Isolation Valve (MSIV) failure, and PZR spray failure. The information flow rate is obtained for each diagnosis task by imposing time limit restrictions for the tasks. Subjective methods require the operators to respond to questionnaires to rate their level of mental effort. NASA-TLX and MCH scale are selected as subjective methods. NASA-TLX is a subjective method used in the various fields including the aviation, automobile, and nuclear industries. It has a multi-dimensional rating technique and provides an overall workload score based on a weighted average on six subscales using pair-wise comparison tests. MCH, on the other hand, is one-dimensional and uses a 10- point rating technique. As with NASA-TLX, the higher the score is, the higher the subjective workload is. For the physiological measurements, an eye tracking system analyzes

  15. Investigating the relationship between tree heights derived from SIBBORK forest model and remote sensing measurements

    Science.gov (United States)

    Osmanoglu, B.; Feliciano, E. A.; Armstrong, A. H.; Sun, G.; Montesano, P.; Ranson, K.

    2017-12-01

    Tree heights are one of the most commonly used remote sensing parameters to measure biomass of a forest. In this project, we investigate the relationship between remotely sensed tree heights (e.g. G-LiHT lidar and commercially available high resolution satellite imagery, HRSI) and the SIBBORK modeled tree heights. G-LiHT is a portable, airborne imaging system that simultaneously maps the composition, structure, and function of terrestrial ecosystems using lidar, imaging spectroscopy and thermal mapping. Ground elevation and canopy height models were generated using the lidar data acquired in 2012. A digital surface model was also generated using the HRSI technique from the commercially available WorldView data in 2016. The HRSI derived height and biomass products are available at the plot (10x10m) level. For this study, we parameterized the SIBBORK individual-based gap model for Howland forest, Maine. The parameterization was calibrated using field data for the study site and results show that the simulated forest reproduces the structural complexity of Howland old growth forest, based on comparisons of key variables including, aboveground biomass, forest height and basal area. Furthermore carbon cycle and ecosystem observational capabilities will be enhanced over the next 6 years via the launch of two LiDAR (NASA's GEDI and ICESAT 2) and two SAR (NASA's ISRO NiSAR and ESA's Biomass) systems. Our aim is to present the comparison of canopy height models obtained with SIBBORK forest model and remote sensing techniques, highlighting the synergy between individual-based forest modeling and high-resolution remote sensing.

  16. Investigating the Relationship between Ethnic Consciousness, Racial Discrimination and Self-Rated Health in New Zealand

    Science.gov (United States)

    Harris, Ricci; Cormack, Donna; Stanley, James; Rameka, Ruruhira

    2015-01-01

    In this study, we examine race/ethnic consciousness and its associations with experiences of racial discrimination and health in New Zealand. Racism is an important determinant of health and cause of ethnic inequities. However, conceptualising the mechanisms by which racism impacts on health requires racism to be contextualised within the broader social environment. Race/ethnic consciousness (how often people think about their race or ethnicity) is understood as part of a broader assessment of the ‘racial climate’. Higher race/ethnic consciousness has been demonstrated among non-dominant racial/ethnic groups and linked to adverse health outcomes in a limited number of studies. We analysed data from the 2006/07 New Zealand Health Survey, a national population-based survey of New Zealand adults, to examine the distribution of ethnic consciousness by ethnicity, and its association with individual experiences of racial discrimination and self-rated health. Findings showed that European respondents were least likely to report thinking about their ethnicity, with people from non-European ethnic groupings all reporting relatively higher ethnic consciousness. Higher ethnic consciousness was associated with an increased likelihood of reporting experience of racial discrimination for all ethnic groupings and was also associated with fair/poor self-rated health after adjusting for age, sex and ethnicity. However, this difference in health was no longer evident after further adjustment for socioeconomic position and individual experience of racial discrimination. Our study suggests different experiences of racialised social environments by ethnicity in New Zealand and that, at an individual level, ethnic consciousness is related to experiences of racial discrimination. However, the relationship with health is less clear and needs further investigation with research to better understand the racialised social relations that create and maintain ethnic inequities in health in

  17. Investigation of the relationship between mean platelet volume and obstructive sleep apnea syndrome

    Directory of Open Access Journals (Sweden)

    Ersin Şükrü Erden

    2013-12-01

    Full Text Available Objective: Obstructive sleep apnea syndrome (OSAS is characterized by recurrent upper airway obstruction and intermittent hypoxia during sleep. Intermittent hypoxia and increased inflammatory activity plays a role in increased risk of cardiovascular disease in the OSAS. OSAS is an important cause of morbidity and mortality and cardiovascular disorders are the most important complications of OSAS. Mean platelet volume (MPV is a marker of platelet activation and function, and increased platelet volume is associated with increased platelet activity. Different diseases related with inflammation, hypoxia, vascular injury, thrombosis and atherosclerosis were found to be associated with MPV. In this study, we aimed to investigate the relationship between OSAS and MPV. Methods: In this retrospective study, data of sex and age matched 33 patients with moderate OSAS, 34 patients with severe OSAS and 30 healthy subjects were evaluated. Results: The mean MPV was found in control, moderate OSAS and severe OSAS groups as 7.83±1.00, 8.26±1.40 and 8.94±1.20 (fL respectively. The mean MPV value was significantly higher in severe OSAS group than control subjects (p=0.001. In correlation analysis, there were positive correlation between MPV with apnea-hypopnea index and total sleep time, and negative correlation between MPV with platelet count and minimum oxygen saturation (Respectively, p=0.003 / R=0.295, p=0.030 / R=0.221, p=0.011 / R= -0.257, p=0.019 / R= -0.238. Conclusion: In this study, the increased MPV was associated with severe OSAS and the results of this study suggest that the platelet activation is increased in OSAS. Hypoxia caused by OSAS, due to the activated platelets, may play a role in the development of cardiovascular diseases which is an important cause of morbidity and mortality in OSAS. J Clin Exp Invest 2013; 4 (4: 492-496

  18. Combination Across Domains: An MEG Investigation into the Relationship between Mathematical, Pictorial, and Linguistic Processing

    Science.gov (United States)

    Bemis, Douglas K.; Pylkkänen, Liina

    2013-01-01

    Debates surrounding the evolution of language often hinge upon its relationship to cognition more generally and many investigations have attempted to demark the boundary between the two. Though results from these studies suggest that language may recruit domain-general mechanisms during certain types of complex processing, the domain-generality of basic combinatorial mechanisms that lie at the core of linguistic processing is still unknown. Our previous work (Bemis and Pylkkänen, 2011, 2012) used magnetoencephalography to isolate neural activity associated with the simple composition of an adjective and a noun (“red boat”) and found increased activity during this processing localized to the left anterior temporal lobe (lATL), ventro-medial prefrontal cortex (vmPFC), and left angular gyrus (lAG). The present study explores the domain-generality of these effects and their associated combinatorial mechanisms through two parallel non-linguistic combinatorial tasks designed to be as minimal and natural as the linguistic paradigm. In the first task, we used pictures of colored shapes to elicit combinatorial conceptual processing similar to that evoked by the linguistic expressions and find increased activity again localized to the vmPFC during combinatorial processing. This result suggests that a domain-general semantic combinatorial mechanism operates during basic linguistic composition, and that activity generated by its processing localizes to the vmPFC. In the second task, we recorded neural activity as subjects performed simple addition between two small numerals. Consistent with a wide array of recent results, we find no effects related to basic addition that coincide with our linguistic effects and instead find increased activity localized to the intraparietal sulcus. This result suggests that the scope of the previously identified linguistic effects is restricted to compositional operations and does not extend generally to all tasks that are merely similar

  19. Regression methods to investigate the relationship between facial measurements and widths of the maxillary anterior teeth.

    Science.gov (United States)

    Isa, Zakiah Mohd; Tawfiq, Omar Farouq; Noor, Norliza Mohd; Shamsudheen, Mohd Iqbal; Rijal, Omar Mohd

    2010-03-01

    In rehabilitating edentulous patients, selecting appropriately sized teeth in the absence of preextraction records is problematic. The purpose of this study was to investigate the relationships between some facial dimensions and widths of the maxillary anterior teeth to potentially provide a guide for tooth selection. Sixty full dentate Malaysian adults (18-36 years) representing 2 ethnic groups (Malay and Chinese), with well aligned maxillary anterior teeth and minimal attrition, participated in this study. Standardized digital images of the face, viewed frontally, were recorded. Using image analyzing software, the images were used to determine the interpupillary distance (IPD), inner canthal distance (ICD), and interalar width (IA). Widths of the 6 maxillary anterior teeth were measured directly from casts of the subjects using digital calipers. Regression analyses were conducted to measure the strength of the associations between the variables (alpha=.10). The means (standard deviations) of IPD, IA, and ICD of the subjects were 62.28 (2.47), 39.36 (3.12), and 34.36 (2.15) mm, respectively. The mesiodistal diameters of the maxillary central incisors, lateral incisors, and canines were 8.54 (0.50), 7.09 (0.48), and 7.94 (0.40) mm, respectively. The width of the central incisors was highly correlated to the IPD (r=0.99), while the widths of the lateral incisors and canines were highly correlated to a combination of IPD and IA (r=0.99 and 0.94, respectively). Using regression methods, the widths of the anterior teeth within the population tested may be predicted by a combination of the facial dimensions studied. (c) 2010 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

  20. Investigation of Ureaplasma urealyticum biovars and their relationship with antimicrobial resistance

    Directory of Open Access Journals (Sweden)

    Zhu Chang-tai

    2011-01-01

    Full Text Available Purpose: To develop Taqman fluorescence quantitative polymerase chain reaction (PCR method for investigating the characteristics of the distributions of Ureaplasma urealyticum (UU biovars and to explore the relationship between UU biovars and antimicrobial resistance. Materials and Methods: By the method of culture, Ureaplasma species were detected. Taqman fluorescence quantitative PCR for detecting UU biovars were developed and UU clinical isolates were detected to distinguish biovars. The broth micro-dilution susceptibility testing methods were used to determine UU susceptibility. Results: By Taqman PCR method, UU biovars was successfully detected. Of 126 samples, biovar 1 was found in 73 (57.94%. There was a statistical difference between genital-urinary tract infection group and asymptomatic group (P<0.05. In the region, UU biovar 1 to 9 kinds of agents kept higher susceptibility rates, but biovar 2 maintained higher susceptibility rates only to tetracyclines. Compared with biovar 1, UU biovar 2 resistance rates to 7 kinds of agents were higher (P<0.05. Conclusions: (1 Our new established Taqman PCR method is a useful tool for screening UU biovars. (2 UU biovar 1 predominated in asymptomatic population; whereas in genital-urinary tract infection population UU biovar 2 had a higher proportion. (3 The characteristics of drug resistance were different between UU biovars. Overall, both two biovars remained higher susceptibility rates to tetracyclines. A majority of biovor 1 strains were sensitive to macrolides and quinolones; while only a small number of biovar 2 strains kept sensitive to roxithromycin and quinolones, a large proportion of biovar 2 strains were found in intermediate ranges.

  1. Adsorption of s-triazines onto polybenzimidazole: A quantitative structure-property relationship investigation

    Energy Technology Data Exchange (ETDEWEB)

    D' Archivio, Angelo Antonio, E-mail: angeloantonio.darchivio@univaq.it [Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universita degli Studi dell' Aquila, Via Vetoio, 67010 Coppito, L' Aquila (Italy); Incani, Angela; Mazzeo, Pietro; Ruggieri, Fabrizio [Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universita degli Studi dell' Aquila, Via Vetoio, 67010 Coppito, L' Aquila (Italy)

    2009-09-21

    The adsorption of 25 symmetric triazines (s-triazines) on polybenzimidazole (PBI) beads is investigated under equilibrium (batch) conditions. The observed adsorption isotherms of the selected compounds are accurately described by the Freundlich model, while the agreement between the Langmuir model and the experimental data is moderately worse, which seems to reflect the heterogeneous meso- and micro-porosity of PBI and polydispersion in the interaction mechanism. Methylthio- and methoxytriazines exhibit a greater adsorption tendency as compared with chlorotriazines, moreover, progressive dealkylation of amino groups results in a progressive increase of triazine uptake on PBI. Based on these evidences, the adsorption mechanism seems to be governed by a combination of {pi}-{pi} and hydrogen-bonding interactions. Genetic algorithm (GA) variable selection and multilinear regression (MLR) are combined in order to describe the effect of triazine structure on the extraction performance of PBI according to the quantitative structure-property relationship (QSPR) method. q{sub max}, the amount of triazine adsorbed per weight unit of PBI assuming homogeneous monolayer (Langmuir) mechanism, exhibits a great variability within the set of investigated triazines and is the quantity here modelled by QSPR. On the other hand, the Freundlich constant, K{sub F}, which expresses the adsorption efficiency under multilayer heterogeneous conditions, even if markedly increases passing from chloro- to methylthio- or methoxytriazines, is less noticeably affected by the fine details of the adsorbate structure, as the number or nature of alkyl fragments bound to the amino groups. To quantitatively relate q{sub max} with the triazine structure GA-MLR analysis is performed on the set of 1664 theoretical molecular descriptors provided by the software Dragon. Finally, a four-dimensional QSPR model is selected based on leave-one-out cross-validation and its prediction ability is further tested on

  2. Adsorption of s-triazines onto polybenzimidazole: A quantitative structure-property relationship investigation

    International Nuclear Information System (INIS)

    D'Archivio, Angelo Antonio; Incani, Angela; Mazzeo, Pietro; Ruggieri, Fabrizio

    2009-01-01

    The adsorption of 25 symmetric triazines (s-triazines) on polybenzimidazole (PBI) beads is investigated under equilibrium (batch) conditions. The observed adsorption isotherms of the selected compounds are accurately described by the Freundlich model, while the agreement between the Langmuir model and the experimental data is moderately worse, which seems to reflect the heterogeneous meso- and micro-porosity of PBI and polydispersion in the interaction mechanism. Methylthio- and methoxytriazines exhibit a greater adsorption tendency as compared with chlorotriazines, moreover, progressive dealkylation of amino groups results in a progressive increase of triazine uptake on PBI. Based on these evidences, the adsorption mechanism seems to be governed by a combination of π-π and hydrogen-bonding interactions. Genetic algorithm (GA) variable selection and multilinear regression (MLR) are combined in order to describe the effect of triazine structure on the extraction performance of PBI according to the quantitative structure-property relationship (QSPR) method. q max , the amount of triazine adsorbed per weight unit of PBI assuming homogeneous monolayer (Langmuir) mechanism, exhibits a great variability within the set of investigated triazines and is the quantity here modelled by QSPR. On the other hand, the Freundlich constant, K F , which expresses the adsorption efficiency under multilayer heterogeneous conditions, even if markedly increases passing from chloro- to methylthio- or methoxytriazines, is less noticeably affected by the fine details of the adsorbate structure, as the number or nature of alkyl fragments bound to the amino groups. To quantitatively relate q max with the triazine structure GA-MLR analysis is performed on the set of 1664 theoretical molecular descriptors provided by the software Dragon. Finally, a four-dimensional QSPR model is selected based on leave-one-out cross-validation and its prediction ability is further tested on four

  3. INVESTIGATION OF THE FREQUENCY-TEMPERATURE RELATIONSHIP OF THE DIELECTRIC PERMITTIVITY OF THE PZT PIEZOCERAMICS IN THE LOW FREQUENCY RANGE

    Directory of Open Access Journals (Sweden)

    A. I. ZOLOTAREVSKIY

    2018-05-01

    Full Text Available Purpose. To investigate the frequency-temperature relationship of the dielectric permittivity of PZT piezoceramics in the low frequency range. Methodology. To obtain the frequency-temperature relationship of the dielectric permittivity of the PZT piezoceramics, a technique was used to determine the capacitance of the capacitor, between which plates the sample was placed. The value of the dielectric permittivity of the sample was calculated from the capacitor capacitance obtained. Findings. The frequency-temperature relationship of the dielectric permittivity of the PZT piezoceramics in the low frequency range has been obtained by the authors. The dielectric permittivity is not practically related to the frequency of the alternating voltage at a low temperature, with increasing in temperature its value increases and frequency relationship is observed. The temperature relationship of the dielectric permittivity of the PZT piezoceramics is satisfactorily described by the exponential functional dependence in the low-temperature range. The activation energy of the PZT piezoceramics polarization is determined from the graph of the dependence of the logarithm of the dielectric permittivity upon the inverse temperature. Different values of the activation energy for the two temperature regions prove on the existence of different mechanisms of the PZT piezoceramics polarization in the temperature range being investigated. Originality. The authors investigated the frequency-temperature relationship of the dielectric permittivity of the PZT piezoceramics in the low-frequency range. It is established that the temperature relationship of the dielectric permittivity of the PZT piezoceramics is satisfactorily described by an exponential functional relationship in the lowtemperature range. The activation energy of polarization is determined for two temperature sections. Practical value. The research results can be used to study the mechanism of polarization of

  4. Light at the end of the tunnel. Chances for the investigation of nonlinear dose-risk relationships

    International Nuclear Information System (INIS)

    Harder, D.

    2008-01-01

    The present contribution aims at illustrating the chances to gain a new comprehension of dose-risk relationships by investigating radiation actions in the promotion and progression phases of carcinogenesis. The mechanisms of the accumulation of somatic mutations and of the immunosurveillance of neoplastic cell clones are clearly consistent with nonlinear dose-risk relationships. Furthermore, a reminder is given of the possibility, existing in the neighbourhood of Chernobyl, of investigating the evolutionary adaption of organisms to chronic low-level radiation exposure. (orig.)

  5. An Investigation into the Relationship between Human Cranial and Pelvic Sexual Dimorphism.

    Science.gov (United States)

    Best, Kaleigh C; Garvin, Heather M; Cabo, Luis L

    2017-10-16

    When faced with commingled remains, it might be assumed that a more "masculine" pelvis is associated with a more "masculine" cranium, but this relationship has not been specifically tested. This study uses geometric morphometric analyses of pelvic and cranial landmarks to assess whether there is an intra-individual relationship between the degrees of sexual expression in these two skeletal regions. Principal component and discriminant function scores were used to assess sexual dimorphism in 113 U.S. Black individuals. Correlation values and partial least squares regression (PLS) were used to evaluate intra-individual relationships. Results indicate that the os coxae is more sexually dimorphic than the cranium, with element shape being more sexually dimorphic than size. PLS and correlation results suggest no significant intra-individual relationship between pelvic and cranial sexual size or shape expression. Thus, in commingled situations, associations between these skeletal elements cannot be inferred based on degree of "masculinity." © 2017 American Academy of Forensic Sciences.

  6. A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

    Science.gov (United States)

    Harrell, William A; Vieira, Rebecca C; Ensel, Susan M; Montgomery, Vicki; Guernieri, Rebecca; Eccard, Vanessa S; Campbell, Yvette; Roxas-Duncan, Virginia; Cardellina, John H; Webb, Robert P; Smith, Leonard A

    2017-02-01

    Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC 50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay. Published by Elsevier Ltd.

  7. Structure-activity relations of 2-(methylthio)benzimidazole by FTIR, FT-Raman, NMR, DFT and conceptual DFT methods.

    Science.gov (United States)

    Arjunan, V; Raj, Arushma; Ravindran, P; Mohan, S

    2014-01-24

    The vibrational fundamental modes of 2-(methylthio)benzimidazole (2MTBI) have been analysed by combining FTIR, FT-Raman and quantum chemical calculations. The structural parameters of the compound are determined from the optimised geometry by B3LYP with 6-31G(∗∗), 6-311++G(∗∗) and cc-pVTZ basis sets and giving energies, harmonic vibrational frequencies, depolarisation ratios, IR intensities and Raman activities. (1)H and (13)C NMR spectra have been analysed and (1)H and (13)C nuclear magnetic resonance chemical shifts are calculated using the gauge independent atomic orbital (GIAO) method. The structure-activity relationship of the compound is also investigated by conceptual DFT methods. The chemical reactivity and site selectivity of the molecule has been determined with the help of global and local reactivity descriptors. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Biological and structure-activity evaluation of chalcone derivatives against bacteria and fungi

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Wender A.; Andrade, Carlos Kleber Z.; Napolitano, Hamilton B., E-mail: wender@unb.br, E-mail: ckleber@unb.br [Universidade de Brasilia (LaQMOS/UnB), DF (Brazil). Inst. de Quimica; Vencato, Ivo; Castro, Miriam R.C. de; Camargo, Ademir J. [Universidade Estadual de Goias (UEG), Anapolis, GO (Brazil). Ciencias Exatas e Tecnologicas; Lariucci, Carlito [Universidade Estadual de Goias (UEG), Goiania, GO (Brazil). Inst. de Fisica

    2013-01-15

    The present work describes the antibacterial and antifungal activities of several chalcones obtained by a straight Claisen-Schmidt aldol condensation determined by the minimal inhibitory concentration against different microorganisms (Gram-positive and Gram-negative bacteria and fungi). Solid state crystal structures of seven chalcones were determined by X-ray diffraction (XRD) analysis. Chemometric studies were carried out in order to identify a potential structure activity relationship. (author)

  9. Investigation Of The Relationship of Eating Attitudes With Thought Shape Fusion, Gender and Body Mass Index

    Directory of Open Access Journals (Sweden)

    Sultan OKUMUSOGLU

    2017-06-01

    Full Text Available Certain patologies are accepted as characterized with relevant certain cognitive distortions. Eating Disorders and Obssessive Compulsive Disorders (OCD are related in terms of comorbidite, existence of similar distortions and intrusive thoughts. Distorted cognitions related with body shape and weight are associated with eating disorders and the distorted cognition which was conceptualised as thought shape fusion is accepted as a version of thought action fusion which is commonly seen at OCD. Because of its practical and theoretical relevance the aim of the present study is investigation of the relationship of eating attitudes of individuals with thought shape fusion cognitive distortion and gender and body mass index (BMI. Participants are 73 university students with age range 18-28 (58 male. Eating Attitudes Test (EAT and Thought Shape Fusion Scale (TSFS have been used for data collection. A positive correlation was found between TSFS and EAT (r= 0.53, p=0.01 and TSFS and BMI (r=0,34, p=0,01. According to stepwise regression analysis primary predictor of TSFS scores are EAT scores; %28 of the variance of the TSFS was explained by EAT scores and when BMI and gender variables are added the explained variance is %47. Women differed with significantly higher means in terms of EAT scores. Groups were formed according to pathology cut point of EAT scale (≥30 and the group above the cut point differed with significantly higher TSFS mean scores. Results of the present study seems parallel with the claims which associates eating disorders with distorted cognitions which are expressions of intrusive thoughts similar to OCD and associated with characteristics of eating disorders as overrating of food, body weight and shape. Findings are evaluated as having practical and theoretical significance. It is hoped that after supported with future studies the findings of the present study will be useful by adding to the existing knowledge in the field which

  10. Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

    Science.gov (United States)

    Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

    2011-06-01

    Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

  11. Mother-grandmother coparenting relationships in families with incarcerated mothers: a pilot investigation.

    Science.gov (United States)

    Baker, Jason; McHale, James; Strozier, Anne; Cecil, Dawn

    2010-06-01

    Using new methods designed to assess coparenting between incarcerated mothers of preschool-aged children and the maternal grandmothers caring for the children during their absence, we examined relationships between coparenting quality during the mother's jail stay and both concurrent child behavior problems and later coparenting interactions following mothers' release and community reentry. Forty mother-grandmother dyads participated in joint coparenting discussions during the incarceration, with a smaller subset completing a parallel activity at home 1 month postrelease. Both women also participated in individual coparenting interviews during the incarceration, and reported on child behavior problems. Mother-grandmother coparenting interactions exhibited an overall structure similar to that documented in nuclear families, with population-specific dynamics also evident. The observational system demonstrated good interrater and internal reliability, and showed associations with maternal (but not grandmother) reports and descriptions of the coparenting relationship via interview. Greater coparenting relationship quality during incarceration was associated with fewer concurrent child externalizing behavior problems, and predicted more positive coparenting interactions postrelease. Findings suggest that the coparenting assessments were useful for understanding mother-grandmother coparenting relationships in these families and that importantly, these relationships were tied to children's functioning. Avenues for future research and considerations for intervention efforts are discussed.

  12. An investigation into the multifaceted relationship between gratitude, empathy, and compassion

    Directory of Open Access Journals (Sweden)

    Grace Y. Kim

    2018-01-01

    Full Text Available The virtues of gratitude, empathy, and compassion are associated with various psychological and relational benefits. Past research suggests that gratitude and empathy are correlated and that compassion is in fact derived from empathy. However, limited research exists concerning the direct relationship between gratitude and compassionate love (i.e., a more enduring form of compassion. This study examined the relationship between the two constructs, with empathy as a potential mediator in this relationship. Two hundred undergraduate students from a religiously affiliated university were recruited and completed an online, multi-section questionnaire that includes measures of gratitude, empathy, and compassionate love. Statistical analyses revealed a significant partial mediation effect, with gratitude being both directly and indirectly (via empathy associated with compassionate love. In other words, higher levels of gratitude produced greater compassionate love through increased feelings of empathy. Further analyses indicated that among the three types of empathy explored (cognitive empathy, emotional contagion, and emotional disconnection, cognitive empathy best mediated the relationship between gratitude and compassionate love. These findings have important implications in both a clinical and research context, including the utilization of gratitude and empathy interventions to increase protection against clinician burnout and improve client health and well-being. Future research is warranted in further exploring the relationship among these variables utilizing more objective forms of measurement.

  13. Artificial Microstructures to Investigate Microstructure-Property Relationships in Metallic Glasses

    Science.gov (United States)

    Sarac, Baran

    Technology has evolved rapidly within the last decade, and the demand for higher performance materials has risen exponentially. To meet this demand, novel materials with advanced microstructures have been developed and are currently in use. However, the already complex microstructure of technological relevant materials imposes a limit for currently used development strategies for materials with optimized properties. For this reason, a strategy to correlate microstructure features with properties is still lacking. Computer simulations are challenged due to the computing size required to analyze multi-scale characteristics of complex materials, which is orders of magnitude higher than today's state of the art. To address these challenges, we introduced a novel strategy to investigate microstructure-property relationships. We call this strategy "artificial microstructure approach", which allows us to individually and independently control microstructural features. By this approach, we defined a new way of analyzing complex microstructures, where microstructural second phase features were precisely varied over a wide range. The artificial microstructures were fabricated by the combination of lithography and thermoplastic forming (TPF), and subsequently characterized under different loading conditions. Because of the suitability and interesting properties of metallic glasses, we proposed to use this toolbox to investigate the different deformation modes in cellular structures and toughening mechanism in metallic glass (MG) composites. This study helped us understand how to combine the unique properties of metallic glasses such as high strength, elasticity, and thermoplastic processing ability with plasticity generated from heterostructures of metallic glasses. It has been widely accepted that metallic glass composites are very complex, and a broad range of contributions have been suggested to explain the toughening mechanism. This includes the shear modulus, morphology

  14. An Investigation of the Relationship between High-School Students' Problematic Mobile Phone Use and Their Self-Esteem Levels

    Science.gov (United States)

    Isiklar, Abdullah; Sar, Ali Haydar; Durmuscelebi, Mustafa

    2013-01-01

    Excessive mobile phone use, especially among adolescents, brings too many debates about its effects. To this end, in this study, we try to investigate the relationship between adolescents' mobile phone use and their self-esteem levels with regard to their genders. For 919 high school students, we evaluated mobile phone use concerning their…

  15. Investigation of the Relationship between Communication Skills, Social Competence and Emotion Regulation Skills of Preschool Children in Turkey

    Science.gov (United States)

    Dagal, A. B.

    2017-01-01

    The aim of this study is to investigate the relationship between communication skills, social competence and emotion regulation skills of preschool children. Children attending public primary schools who were 53 to 80 months old from the middle socio-economic class were chosen randomly from Istanbul City center districts for this study. They were…

  16. An Investigation of the Relationship between Iranian EFL Learners' Cultural Intelligence and Their Performance on the IELTS Listening Modules

    Science.gov (United States)

    Rafie, Arezoo; Khosravi, Robab; Nasiri, Mahdi

    2016-01-01

    This study aimed to investigate the relationship between Iranian EFL Learners' Cultural intelligence (CQ) and their performance on the IELTS Listening Module. Sixty advanced EFL students majoring in English translation at University of Zanjan were matched for the study through the Oxford Quick Placement Test. Cultural Intelligence Scale developed…

  17. An Investigation of the Relationship between Digital Citizenship Levels of Pre-Service Primary School Teachers and Their Democratic Values

    Science.gov (United States)

    Aladag, Soner; Çiftci, Serdar

    2017-01-01

    This study seeks to investigate the relationship between digital citizenship levels of pre-service primary school teachers and their democratic values. The research was designed in descriptive survey model. The research was conducted with the participation of 346 pre-service primary school teachers (juniors and seniors) from Adnan Menderes…

  18. Investigating the Relationship between Job Satisfaction Levels of the Teachers in Educational Institutions and Their Attitudes towards Teaching Profession

    Science.gov (United States)

    Üredi, Lütfi

    2017-01-01

    The basic purpose of this research was to investigate the relationship between job satisfaction levels of the teachers in educational institutions and their attitudes towards teaching profession. Obtained results provided significant contributions for improving the quality of educational activities. Relational screening model as one of the…

  19. When Relationships Depicted Diagrammatically Conflict with Prior Knowledge: An Investigation of Students' Interpretations of Evolutionary Trees

    Science.gov (United States)

    Novick, Laura R.; Catley, Kefyn M.

    2014-01-01

    Science is an important domain for investigating students' responses to information that contradicts their prior knowledge. In previous studies of this topic, this information was communicated verbally. The present research used diagrams, specifically trees (cladograms) depicting evolutionary relationships among taxa. Effects of college…

  20. Investigating the Relationship between Test Preparation and "TOEFL iBT"® Performance. Research Report. ETS RR-14-15

    Science.gov (United States)

    Liu, Ou Lydia

    2014-01-01

    This study investigates the relationship between test preparation and test performance on the "TOEFL iBT"® exam. Information on background variables and test preparation strategies was gathered from 14,593 respondents in China through an online survey. A Chinese standardized English test was used as a control for prior English ability.…

  1. Investigating the Mediator role of Social Safeness on the Relationship between Forgiveness and Life Satisfaction

    Directory of Open Access Journals (Sweden)

    Umran Akin

    Full Text Available The aim of the present study is to examine the mediating effect of social safeness on the relationship between forgiveness and life satisfaction. Participants were 311 university students who completed a questionnaire package that included the Trait Forgiveness Scale, the Social Safeness and Pleasure Scale, and the Life Satisfaction Scale. According to the results, social safeness and life satisfaction were predicted positively by forgiveness. On the other hand, life satisfaction was predicted positively by social safeness. In addition, social safeness mediated on the relationship between forgiveness and life satisfaction. The results were discussed in the light of the related literature and dependent recommendations to the area were given.

  2. Investigation the Relationship between Goal Orientation and Parenting Styles among Sample of Jordanian University Students

    Science.gov (United States)

    Mahasneh, Ahmad M.

    2014-01-01

    The primary purpose of this study is to examine the relationship between goal orientation and parenting styles. Participants of the study completed 650 goal orientation and parenting styles questionnaires. Means, standard deviations, regression and correlation analysis were used for data in establishing the dependence of the two variables. Results…

  3. Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

    NARCIS (Netherlands)

    Feng, Yen Chen Anne; Cho, Kelly; Lindstrom, Sara; Kraft, Peter; Cormack, Jean; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Gruber, Stephen B.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Peters, Ulrike; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos-Santos-Silva, Isabel; Hunter, David J.; Lindström, Sara; Kraft, Peter; Ahsan, Habib; Whittemore, Alice S.; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Uitterlinden, Andre G; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare A.; Rahman, Nazneen; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham G.; Severi, Gianluca; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth C.; Riboli, Elio; Kraft, Peter; Hunter, David J.; Gapstur, Susan M.; Berndt, Sonja I.; Chanock, Stephen J.; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil E; Landi, Maria Teresa; Heinrich, Joachim; Risch, Angela; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.; Amos, Christopher I; Liang, Liming; Driver, Jane A.; IGAP Consortium, Colorectal Transdisciplinary Study (CORECT); Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE)

    2017-01-01

    Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer’s disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from

  4. Investigating the Relationship between School Level and a School Growth Mindset

    Science.gov (United States)

    Hanson, Janet; Ruff, William; Bangert, Arthur

    2016-01-01

    This study explored the relationship between school level and the psychosocial construct of a growth mindset school culture. Data was collected on the What's My School Mindset (WMSM) Survey from a stratified random sample of PK-12 faculty and administrators (n = 347) in 30 schools across a large northwestern state. The overarching research…

  5. Investigating the Relationships between Approaches to Learning, Learner Identities and Academic Achievement in Higher Education

    Science.gov (United States)

    Herrmann, K. J.; Bager-Elsborg, A.; McCune, V.

    2017-01-01

    This paper considers relationships between approaches to learning, learner identities, self-efficacy beliefs and academic achievement in higher education. In addition to already established survey instruments, a new scale, "subject area affinity," was developed. The scale explores the extent to which students identify with their area of…

  6. Investigating the Relationship between Self-Handicapping Tendencies, Self-Esteem and Cognitive Distortions

    Science.gov (United States)

    Yavuzer, Yasemin

    2015-01-01

    The purpose of this study is to examine the relationship between cognitive distortions, self-handicapping tendencies, and self-esteem in a sample of students studying in a school of education. The sample of the study was comprised of 507 volunteer students chosen through random sampling from a total of 4,720 students who were studying teaching at…

  7. Investigating the Relationship between Educational Stress and Emotional Self-Efficacy

    Science.gov (United States)

    Arslan, Nihan

    2017-01-01

    The objective of study is the underlying to relationship between emotional self-efficacy and educational stress with a structural equation model. The research was conducted on 232 secondary school students. Emotional self-efficacy scale and educational stress scale were used in the study. It was found that there was a negative correlation between…

  8. Investigating the Relationship between Coupon Collecting and Top-of-Mind Brand Awareness.

    Science.gov (United States)

    Pokrywczynski, Jim

    To determine if coupon collecting has any influence on product information processing like brand awareness, and to understand better the coupon collecting process, an exploratory study examined the relationship between coupon-collecting behavior and brand awareness for the coupons collected. Subjects, 152 randomly chosen respondents from a Midwest…

  9. Investigating the Relationship between Confucianism and Leadership: A Comparative Study of University Faculty

    Science.gov (United States)

    Schenck, Andrew

    2018-01-01

    This article describes how due to the potential impact of cultural factors on leadership, further research of foreign contexts is needed. A study was designed to examine relationships between Confucian values and leadership preferences in a South Korean context. First, the Vannsimpco Leadership Survey (VLS) was given to faculty from both a South…

  10. An Investigation of Relationships among Instructor Immediacy and Affective and Cognitive Learning in the Online Classroom

    Science.gov (United States)

    Baker, Jason D.

    2004-01-01

    A significant body of literature has supported the assertion that communication in the classroom is central to the learning process. Prosocial behaviors, such as nonverbal and verbal immediacy, have been found to promote affective and cognitive learning in traditional instructional settings. This study examined the relationships among instructor…

  11. An Investigation into the Relationship between Academic Risk Taking and Chemistry Laboratory Anxiety in Turkey

    Science.gov (United States)

    Öner Sünkür, Meral

    2015-01-01

    This study evaluates the relationship between academic risk taking and chemistry laboratory anxiety using a relational scanning model. The research sample consisted of 127 undergraduate students (sophomores, juniors and seniors) in the Chemistry Teaching Department at Dicle University. This research was done in the spring semester of the 2012 to…

  12. The role of the follower in the relationship between empowering leadership and empowerment: A longitudinal investigation

    NARCIS (Netherlands)

    van Dierendonck, D.; Dijkstra, M.T.M.

    2012-01-01

    The purpose of this longitudinal study among 212 Dutch prison officers was to enhance insight into the nature of the relationship between empowering leader behavior and follower psychological empowerment. Empowerment was conceptualized as intrinsic task motivation, manifested in a set of 4

  13. Investigating the Relationship of Resilience to Academic Persistence in College Students with Mental Health Issues

    Science.gov (United States)

    Hartley, Michael T.

    2013-01-01

    In this study, the relationships between measures of inter- and intrapersonal resilience and mental health were examined with respect to academic persistence in college students with mental health issues. A sample of 121 undergraduate students with mental health issues was recruited from campus mental health offices offering college counseling,…

  14. The Sport Commitment Model: An Investigation of Structural Relationships with Thai Youth Athlete Populations

    Science.gov (United States)

    Choosakul, Chairat; Vongjaturapat, Naruepon; Li, Fuzhong; Harmer, Peter

    2009-01-01

    Grounded in the conceptual framework of the Sport Commitment Model and previous empirical studies conducted in Western countries, this study was designed to (a) test and validate a Thai version of the Athlete Opinion Survey to assess components of the Sport Commitment Model in Thai youth athletes and (b) examine structural relationships among…

  15. An Investigation of the Relationship between Language Learning Strategies and Learning Styles in Turkish Freshman Students

    Science.gov (United States)

    Balci, Özgül

    2017-01-01

    The purpose of this study is to determine the relationship between the language learning strategies of freshman students and their learning styles. This study is a descriptive research and employs a relational screening model. Participants of the study were 328 freshman students majoring in different fields at Necmettin Erbakan University Ahmet…

  16. An Investigation into the Relationship between Cigarette Smoking and Diverticular Disease of the Colon

    OpenAIRE

    Christopher G Jamieson; Michael J Weinberg; Joanne Lorraine

    1990-01-01

    A retrospective study was conducted to determine the relationship between cigarette smoking and diverticular disease of the colon. One hundred and two patients undergoing barium enema were assessed for diverticular disease and smoking history. No significant positive association between smoking and diverticular disease was found.

  17. The Impact of Business Intelligence (BI Competence on Customer Relationship Management (CRM Process: An Empirical Investigation of the Banking Industry

    Directory of Open Access Journals (Sweden)

    Ali Mortezaei

    2018-03-01

    Full Text Available Nowadays, establishing long-term and effective relationships with customers is a key factor in understanding customers’ needs and preferences and achieving competitive advantage. In addition, companies are facing with a growing need for information and analytical knowledge about their customers, market, competitors, organizational environment, and other factors affecting their business. Business intelligence has been considered as a response to this need. The purpose of this study is to investigate the role of business intelligence competence in improving customer relationship management process. Based on the literature review and the competence – capability relationship paradigm, a conceptual model was developed comprising of different dimensions of business intelligence competence and customer relationship management processes. The data were collected from the banking sector and partial least squares structural equation modelling was employed for data analysis. Empirical results showed that organizational business intelligence competence, comprising of managerial, technical, and cultural competence, has a significantly positive impact on enhancing capabilities of customer relationship management process including initiation, maintenance, and termination of the relationship.

  18. An investigation into the relationship between age and physiological function in highly active older adults.

    Science.gov (United States)

    Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

    2015-02-01

    The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55-79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. V̇O2max was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55-79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular

  19. An Investigation into the Relationship between Social Capital ‎and the Nutritional Knowledge of Athletes

    Directory of Open Access Journals (Sweden)

    F. Mohammadi

    2016-02-01

    Full Text Available Nowadays the concept of social capital is one of the most popular concepts in sociological studies. Some experts believe that social capital is among the most important factors with a significant part in individuals’ success in achieving their goals. So, the main purpose of this study is to analyze the relationship between social capital and the nutritional knowledge of athletes. For this purpose, the theoretical framework and hypotheses of the research are set based on Pierre Bourdieu’s theory. The statistical population of the research includes 2300 athletes in the 2014 Sports Championship held at Shahid Beheshti University; 310 persons were selected by means of Morgan’s table and the stratified sampling method. The survey method and questionnaires were employed to collect the data. The findings of the research indicate that there is a positive and significant relationship between social capital and the nutritional knowledge of athletes.

  20. An empirical investigation on the relationship between parenting styles and employees' career adaptability

    Directory of Open Access Journals (Sweden)

    Najmeh Sedrpoushan

    2012-09-01

    Full Text Available The purpose of this study is to determine the relationship between parenting styles and employees' career adaptability. The statistical population includes all employees in Polyacrid's Factory of Isfahan in 2012. The proposed study selects a sample of 321 employees using cluster sampling. The study has used a based on Baumrind's theorem, which maintains three groups of permissive, authoritarian and authoritative in Likert scale. The results of our study have indicated that there is definitely a difference in parenting style among various members in terms of career concern, career curiosity and career confidence but such relationship does not exists in terms of career control. In addition, the study explains that people with permissive parenting style have less career concern, career curiosity and career confidence than those with permissive parenting style do.