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Comparative QSAR analyses of competitive CYP2C9 inhibitors using three-dimensional molecular descriptors

2011Journal article Open access
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dc.contributor.authorLather, Viney
dc.contributor.authorFernandes, Miguel X.
dc.date.accessioned2023-02-09T09:17:15Z
dc.date.available2023-02-09T09:17:15Z
dc.date.issued2011
dc.description.abstractOne of the biggest challenges in QSAR studies using three-dimensional descriptors is to generate the bioactive conformation of the molecules. Com parative QSAR analyses have been performed on a dataset of 34 structurally diverse and competitive CYP2C9 inhibitors by generating their lowest energy conformers as well as additional multiple conformers for the calculation of molecular de scriptors. Three-dimensional descriptors account ing for the spatial characteristics of the molecules calculated using E-Dragon were used as the inde pendent variables. The robustness and the predic tive performance of the developed models were verified using both the internal [leave-one-out (LOO)] and external statistical validation (test set of 12 inhibitors). The best models (MLR using GET AWAY descriptors and partial least squares using 3D-MoRSE) were obtained by using the multiple conformers for the calculation of descriptors and were selected based upon the higher external pre diction (R2 test values of 0.65 and 0.63, respectively) and lower root mean square error of prediction (0.48 and 0.48, respectively). The predictive ability of the best model, i.e., MLR using GETAWAY de scriptors was additionally verified on an external test set of quinoline-4-carboxamide analogs and resulted in an R2 test value of 0.6. These simple and alignment-independent QSAR models offer the possibility to predict CYP2C9 inhibitory activity of chemically diverse ligands in the absence of X-ray crystallographic information of target protein structure and can provide useful insights about the ADMET properties of candidate molecules in the early phases of drug discovery.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationLather, V., & Fernandes, M. X. (2011). Comparative QSAR analyses of competitive CYP2C9 inhibitors using three-dimensional molecular descriptors. Chemical Biology & Drug Design, 78(1), 112-123.pt_PT
dc.identifier.doi10.1111/j.1747-0285.2011.01106.xpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/5018
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationDESIGN AND DEVELOPMENT OF PPARDELTA SELECTIVE LIGANDS USING STRUCTURE BASED AND LIGAND BASED COMPUTATIONAL APPROACHES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subject3D-MoRSEpt_PT
dc.subjectADMETpt_PT
dc.subjectCYP2C9pt_PT
dc.subjectGETAWAYpt_PT
dc.subjectQSARpt_PT
dc.subjectRDFpt_PT
dc.subjectWHIMpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.titleComparative QSAR analyses of competitive CYP2C9 inhibitors using three-dimensional molecular descriptorspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDESIGN AND DEVELOPMENT OF PPARDELTA SELECTIVE LIGANDS USING STRUCTURE BASED AND LIGAND BASED COMPUTATIONAL APPROACHES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/PIDDAC/SFRH%2FBPD%2F30954%2F2006/PT
oaire.citation.endPage123pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage112pt_PT
oaire.citation.titleChemical Biology & Drug Designpt_PT
oaire.citation.volume78pt_PT
oaire.fundingStreamPIDDAC
person.familyNameFernandes
person.givenNameMiguel Xavier
person.identifier.ciencia-idED1D-3C7A-467C
person.identifier.orcid0000-0002-1840-616X
person.identifier.ridA-4373-2013
person.identifier.scopus-author-id35466972500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscovery8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3
relation.isProjectOfPublication5bbc25c3-10da-4766-8031-e547ff90b8de
relation.isProjectOfPublication.latestForDiscovery5bbc25c3-10da-4766-8031-e547ff90b8de

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