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dc.contributor.authorAngel Vega-Teijido, Mauricio-
dc.contributor.authorMaluf, Sarah El Chamy-
dc.contributor.authorBonturi, Camila Ramalho-
dc.contributor.authorSambrano, Julio Ricardo-
dc.contributor.authorVentura, Oscar N.-
dc.date.accessioned2014-12-03T13:11:46Z-
dc.date.accessioned2016-10-25T20:15:06Z-
dc.date.available2014-12-03T13:11:46Z-
dc.date.available2016-10-25T20:15:06Z-
dc.date.issued2014-06-01-
dc.identifierhttp://dx.doi.org/10.1007/s00894-014-2254-0-
dc.identifier.citationJournal Of Molecular Modeling. New York: Springer, v. 20, n. 6, 14 p., 2014.-
dc.identifier.issn1610-2940-
dc.identifier.urihttp://hdl.handle.net/11449/113530-
dc.identifier.urihttp://acervodigital.unesp.br/handle/11449/113530-
dc.description.abstractSeveral cellular disorders have been related to the overexpression of the cysteine protease cathepsin B (CatB), such as rheumatic arthritis, muscular dystrophy, osteoporosis, Alzheimer's disease, and tumor metastasis. Therefore, inhibiting CatB may be a way to control unregulated cellular functions and prevent tissue malformations. The inhibitory action of 1,2,4-thiadiazole (TDZ) derivatives has been associated in the literature with their ability to form disulfide bridges with the catalytic cysteine of CatB. In this work, we present molecular modeling and docking studies of a series of eight 1,2,4-thiadiazole compounds. Substitutions at two positions (3 and 5) on the 1,2,4-thiadiazole ring were analyzed, and the docking scores were correlated to experimental data. A correlation was found with the sequence of scores of four related compounds with different substituents at position 5. No correlation was observed for changes at position 3. In addition, quantum chemistry calculations were performed on smaller molecular models to study the mechanism of inhibition of TDZ at the active site of CatB. All possible protonation states of the ligand and the active site residues were assessed. The tautomeric form in which the proton is located on N2 was identified as the species that has the structural and energetic characteristics that would allow the ring opening of 1,2,4thiadiazole.en
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
dc.description.sponsorshipComision Sectorial de Investigacion Cientifica-CSIC-
dc.description.sponsorshipPrograma de Desarrollo de las Ciencias Basicas-PEDECIBA-
dc.description.sponsorshipAgencia Nacional de Investigacion e Innovacion-ANII-
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
dc.format.extent14-
dc.language.isoeng-
dc.publisherSpringer-
dc.sourceWeb of Science-
dc.subjectCysteine proteaseen
dc.subjectCathepsinen
dc.subjectThiadiazoleen
dc.subjectDockingen
dc.subjectQuantum chemistryen
dc.titleTheoretical insight into the mechanism for the inhibition of the cysteine protease cathepsin B by 1,2,4-thiadiazole derivativesen
dc.typeoutro-
dc.contributor.institutionUniv Republica-
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)-
dc.description.affiliationUniv Republica, Fac Quim, DETEMA, Computat Chem & Biol Grp CCBG, Montevideo 11800, Uruguay-
dc.description.affiliationUniv Estadual Paulista, Dept Matemat, Grp Modelagem & Simulacao Mol GMSM, BR-17033360 Sao Paulo, Brazil-
dc.description.affiliationUnespUniv Estadual Paulista, Dept Matemat, Grp Modelagem & Simulacao Mol GMSM, BR-17033360 Sao Paulo, Brazil-
dc.description.sponsorshipIdCNPq: 473265/2008-7-
dc.description.sponsorshipIdComision Sectorial de Investigacion Cientifica-CSICCSIC/655-
dc.description.sponsorshipIdFAPESP: 09/52188-8-
dc.description.sponsorshipIdFAPESP: 09/52189-4-
dc.identifier.doi10.1007/s00894-014-2254-0-
dc.identifier.wosWOS:000338632200043-
dc.rights.accessRightsAcesso restrito-
dc.relation.ispartofJournal of Molecular Modeling-
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