Search results for "Structure-Activity Relationship"

showing 10 items of 743 documents

Correlation of Pharmacological Properties of a Group of Hypolipaemic Drugs by Molecular Topology

1996

Abstract This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit. The resul…

Molecular modelStereochemistryDegrees of freedom (statistics)Pharmaceutical ScienceModels BiologicalCross-validationLethal Dose 50CorrelationStructure-Activity RelationshipFenofibrateGoodness of fitAnimalsMultiple correlationFuransHypolipidemic AgentsPharmacologyChemistryBlood ProteinsRegressionRatsCholesterolProbucolStandard errorRegression AnalysisBiological systemProtein BindingJournal of Pharmacy and Pharmacology
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Calculation of binding energy using BLYP/MM for the HIV-1 integrase complexed with the S-1360 and two analogues.

2007

Abstract Integrase (IN) is one of the three human immunodeficiency virus type 1 (HIV-1) enzymes essential for effective viral replication. S-1360 is a potent and selective inhibitor of HIV-1 IN. In this work, we have carried out molecular dynamics (MD) simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approach, to determine the protein–ligand interaction energy for S-1360 and two analogues. Analysis of the MD trajectories reveals that the strongest protein–inhibitor interactions, observed in the three studied complexes, are established with Lys-159 residue and Mg 2+ cation. Calculations of binding energy using BLYP/MM level of theory reveal that there is a direct rela…

Molecular modelStereochemistryProtein ConformationClinical BiochemistryBinding energyPharmaceutical ScienceHIV IntegraseCrystallography X-RayBiochemistryMolecular mechanicsMolecular dynamicsPropaneStructure-Activity RelationshipDrug DiscoveryHumansMagnesiumPyrrolesAmino Acid SequenceHIV Integrase InhibitorsFuransMolecular Biologychemistry.chemical_classificationbiologyChemistryLysineOrganic ChemistryActive siteInteraction energyTriazolesIntegraseEnzymeAmino Acid SubstitutionModels Chemicalbiology.proteinMolecular MedicineBioorganicmedicinal chemistry
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Novel Hydrazine Molecules as Tools To Understand the Flexibility of Vascular Adhesion Protein-1 Ligand-Binding Site: Toward More Selective Inhibitors

2011

Vascular adhesion protein-1 (VAP-1) belongs to a family of amine oxidases. It plays a role in leukocyte trafficking and in amine compound metabolism. VAP-1 is linked to various diseases, such as Alzheimer's disease, psoriasis, depression, diabetes, and obesity. Accordingly, selective inhibitors of VAP-1 could potentially be used to treat those diseases. In this study, eight novel VAP-1 hydrazine derivatives were synthesized and their VAP-1 and monoamine oxidase (MAO) inhibition ability was determined in vitro. MD simulations of VAP-1 with these new molecules reveal that the VAP-1 ligand-binding pocket is flexible and capable of fitting substantially larger ligands than was previously believ…

Monoamine Oxidase InhibitorsProtein ConformationMonoamine oxidaseCHO CellsMolecular Dynamics SimulationLigandsSubstrate SpecificityStructure-Activity RelationshipCricetulusCricetinaeDrug DiscoveryAnimalsHumansMoietyHydrazine (antidepressant)Monoamine OxidaseBinding SitesChemistryMethylationAdhesionbacterial infections and mycosesIn vitroRatsrespiratory tract diseasesHydrazinesBiochemistryMolecular MedicineAmine gas treatingAmine Oxidase (Copper-Containing)SelectivityCell Adhesion MoleculesJournal of Medicinal Chemistry
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The Antigerminative Activity of Twenty-Seven Monoterpenes

2010

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MonoterpenePharmaceutical ScienceRaphanusphytotoxicityBiologyradicle elongationArticleLepidium sativumRaphanusAnalytical ChemistryBorneollcsh:QD241-441Structure-Activity Relationshipchemistry.chemical_compoundlcsh:Organic chemistryDrug DiscoveryBotanyRadiclePhysical and Theoretical ChemistryCarvoneDose-Response Relationship DrugOrganic Chemistrymonoterpenesfood and beveragesbiology.organism_classificationHorticultureEucalyptolgerminationchemistryChemistry (miscellaneous)GerminationAlcoholsSeedsMonoterpenesMolecular Medicinemonoterpenes; germination; radicle elongation; phytotoxicityGeraniolMolecules
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Predictability and prediction of lowest observed adverse effect levels in a structurally heterogeneous set of chemicals

2005

A database of chronic lowest observed adverse effect levels (LOAELs) for 234 compounds, previously compiled from different sources (Toxicology Letters79, 131-143 (1995)), was modelled using graph theoretical descriptors. This study reveals that data are not homogeneous. Only those data originating from the U.S. Environmental Protection Agency (EPA) reports could be well modelled by multilinear regression (MLR) and linear discriminant analysis (LDA). In contrast, data available from the specific procedures of the National Toxicology Program (NTP) database introduced noise and did not render good models either alone, or in combination with the EPA data.

Multilinear mapComputer scienceLinear modelReproducibility of ResultsContrast (statistics)BioengineeringGeneral MedicineModels TheoreticalLinear discriminant analysiscomputer.software_genreRegressionLowest-observed-adverse-effect levelSet (abstract data type)Structure-Activity RelationshipDrug DiscoveryStatisticsLinear ModelsAnimalsMolecular MedicineData miningOrganic ChemicalsPredictabilityToxicity Tests ChroniccomputerSAR and QSAR in Environmental Research
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Understanding and Controlling Food Protein Structure and Function in Foods: Perspectives from Experiments and Computer Simulations

2020

The structure and interactions of proteins play a critical role in determining the quality attributes of many foods, beverages, and pharmaceutical products. Incorporating a multiscale understanding of the structure–function relationships of proteins can provide greater insight into, and control of, the relevant processes at play. Combining data from experimental measurements, human sensory panels, and computer simulations through machine learning allows the construction of statistical models relating nanoscale properties of proteins to the physicochemical properties, physiological outcomes, and tastes of foods. This review highlights several examples of advanced computer simulations at mol…

MultiscaleInterface interactionsComputer scienceIn silicorare-event method02 engineering and technologyMolecular dynamics01 natural sciencesconstant-pH simulationArticleStructure-Activity RelationshipGPCRruokafoods0103 physical sciencesComputer Simulationcomputer simulationssimulointiravintoaineetProtein-sugar interactionsConstant pH simulationfood proteintilastolliset mallit2. Zero hungerMolecular interactionsCoarse graining010304 chemical physicsQSARFood proteinmolecular dynamicRare-event methodsexperiments021001 nanoscience & nanotechnologyToolboxfysikaaliset ominaisuudetkemialliset ominaisuudetStructure and functionsimulation food carbohydrates pHFoodcoarse grainingmolecular interactionEmulsionsDietary ProteinsproteiinitBiochemical engineeringmaku (aineen ominaisuudet)0210 nano-technologyfysiologiset vaikutuksetFood ScienceAnnual Review of Food Science and Technology
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Structural invariants for the prediction of relative toxicities of polychloro dibenzo-p-dioxins and dibenzofurans

2004

Multivariate models are reported that can predict the relative toxicity of compounds with severe environmental impact, namely polychloro dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Multiple linear regression analysis (MLR) and partial least square projections of latent variables (PLS) show the usefulness of graph-theoretical descriptors, mainly topological charge indices (TCIs), in these series. The general trends of the group are correctly reproduced and better results are presented than have previously been published. In general, the more toxic compounds exhibit more symmetric molecular structures.

Multivariate statisticsCarcinoma HepatocellularPolychlorinated DibenzodioxinsRelative toxicityQuantitative Structure-Activity RelationshipLatent variableDioxinsCatalysisInorganic ChemistryToxicologyComputational chemistryDrug DiscoveryLinear regressionCytochrome P-450 CYP1A1AnimalsSoil PollutantsLeast-Squares AnalysisPhysical and Theoretical ChemistryMolecular BiologyBenzofuransModels StatisticalChemistryOrganic ChemistryReproducibility of Resultsfood and beveragesNeoplasms ExperimentalGeneral MedicineModels TheoreticalRatsDisease Models AnimalModels ChemicalDrug DesignMultivariate AnalysisLinear ModelsEnvironmental PollutantsMultiple linear regression analysisInformation SystemsMolecular Diversity
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Antiproliferative Effects of St. John’s Wort, Its Derivatives, and Other Hypericum Species in Hematologic Malignancies

2021

Hypericumis a widely present plant, and extracts of its leaves, flowers, and aerial elements have been employed for many years as therapeutic cures for depression, skin wounds, and respiratory and inflammatory disorders. Hypericum also displays an ample variety of other biological actions, such as hypotensive, analgesic, anti-infective, anti-oxidant, and spasmolytic abilities. However, recent investigations highlighted that this species could be advantageous for the cure of other pathological situations, such as trigeminal neuralgia, as well as in the treatment of cancer. This review focuses on the in vitro and in vivo antitumor effects of St. John’s Wort (Hypericum perforatum), its derivat…

MyeloidAngiogenesisDrug Evaluation PreclinicalReviewPharmacologylcsh:Chemistrychemistry.chemical_compoundhyperforinDrug InteractionsMyeloid CellsLymphocyteslcsh:QH301-705.5SpectroscopybiologyapoptosisleukemiaHypericum perforatumGeneral MedicineComputer Science ApplicationsHypericinLeukemiamedicine.anatomical_structurephotodynamic therapyHematologic NeoplasmsHypericumHypericumSt. John’s wortlymphomaCatalysisInorganic ChemistryStructure-Activity Relationshipmultidrug resistanceIn vivoCell Line TumormedicineAnimalsHumansPhysical and Theoretical ChemistryMolecular BiologyCell ProliferationPlant Extractsbusiness.industryOrganic Chemistry<i>Hypericum</i>biology.organism_classificationmedicine.diseaseAntineoplastic Agents PhytogenicApoptosis; Hyperforin; Hypericin; Hypericum; Leukemia; Lymphoma; Mul-tidrug resistance; Photodynamic therapy; St. John’s wort; Animals; Antineoplastic Agents Phytogenic; Apoptosis; Cell Line Tumor; Cell Proliferation; Drug Evaluation Preclinical; Drug Interactions; Drug Resistance Neoplasm; Hematologic Neoplasms; Humans; Hypericum; Lymphocytes; Myeloid Cells; Plant Extracts; Structure-Activity RelationshipHyperforinchemistrylcsh:Biology (General)lcsh:QD1-999Drug Resistance NeoplasmhypericinbusinessInternational Journal of Molecular Sciences
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2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.

2004

Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10–40 nM concentrations with minimal cytotoxicity. Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic N…

NNRTI3-Thiazolidin-4-onesAnti-HIV activity13-Thiazolidin-4-oneNNRTIs; 1; 3-Thiazolidin-4-ones; anti-HIVAnti-HIV Agents1Drug Evaluation PreclinicalMutation MissenseBiologyVirus ReplicationVirusStructure-Activity RelationshipVirologyDrug Resistance ViralmedicineStructure–activity relationshipCytotoxicityPharmacologyReverse-transcriptase inhibitorMolecular Structurevirus diseasesanti-HIVSettore CHIM/08 - Chimica FarmaceuticaMolecular biologyIn vitroReverse transcriptaseThiazolesPyrimidinesViral replicationAmino Acid SubstitutionNNRTIsHIV-1Reverse Transcriptase InhibitorsNucleosidemedicine.drugAntiviral research
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Relaxant effects of flavonoids on the mouse isolated stomach: structure-activity relationships.

2008

Flavonoids are a large heterogeneous group of benzo-gamma-pyrone derivatives, which are abundantly present in our diet. In this study we investigated the effects of six flavonoids (apigenin, genistein, quercetin, rutin, naringenin and catechin) on the gastric tone in mouse isolated stomach. The mechanical activity was recorded as changes of intraluminal pressure. All flavonoids tested produced a concentration-dependent relaxation, which was reversible after washout. The relative order of potency of the flavonoids was apigenin> or =genistein>quercetin>naringenin> or =rutin>catechin. Analysis of the chemical structure showed that the relaxant activity was progressively diminished by the prese…

NaringeninMalePotassium ChannelsFlavonoidGenisteinAction PotentialsIn Vitro TechniquesNitric OxideSettore BIO/09 - FisiologiaNitric oxidechemistry.chemical_compoundRutinMiceStructure-Activity RelationshipFlavonoids gastric relaxation smooth muscle potassium channels nitric oxideAnimalsheterocyclic compoundsPharmacologychemistry.chemical_classificationFlavonoidsNeuronsDose-Response Relationship DrugStomachfood and beveragesCatechinMuscle SmoothMice Inbred C57BLchemistryBiochemistryGastric MucosaApigeninProstaglandinsQuercetinMuscle ContractionEuropean journal of pharmacology
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