The Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovani

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dc.contributor.authorRocha, Camila A. [UNESP]
dc.contributor.authorSanches, Paulo R. S. [UNESP]
dc.contributor.authorMarchetto, Reinaldo [UNESP]
dc.contributor.authorZottis, Aderson [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-11-26T16:28:06Z
dc.date.available2018-11-26T16:28:06Z
dc.date.issued2016-03-01
dc.description.abstractThe dihydrobetulinic acid is a known competitive inhibitor of topoisomerase IB from Leishmania donovani, a validated target for developing new antileishmanial drugs. However, its binding mode and interaction pocket have not been established yet. We combined docking and molecular dynamics simulations to identify the most probable binding pocket. Our best model strongly suggests a cavity involving the residues arginine 314 and arginine 410 from chain A, and the catalytic tyrosine 222 from chain B as the interaction site and a substructure of this terpene inhibitor as essential for the process of molecular recognition. Then, a new class of inhibitors with increased affinity could be designed by structure-based approaches.en
dc.description.affiliationUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, CP 355, BR-14800060 Araraquara, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, CP 355, BR-14800060 Araraquara, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipPROPe-UNESP (Young Research)
dc.description.sponsorshipIdFAPESP: 2012/00360-4
dc.format.extent591-598
dc.identifierhttp://dx.doi.org/10.5935/0103-5053.20150295
dc.identifier.citationJournal Of The Brazilian Chemical Society. Sao Paulo: Soc Brasileira Quimica, v. 27, n. 3, p. 591-598, 2016.
dc.identifier.doi10.5935/0103-5053.20150295
dc.identifier.fileS0103-50532016000300591.pdf
dc.identifier.issn0103-5053
dc.identifier.scieloS0103-50532016000300591
dc.identifier.urihttp://hdl.handle.net/11449/161337
dc.identifier.wosWOS:000372466500015
dc.language.isoeng
dc.publisherSoc Brasileira Quimica
dc.relation.ispartofJournal Of The Brazilian Chemical Society
dc.relation.ispartofsjr0,357
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectleishmaniasis
dc.subjecttopoisomerase IB
dc.subjectdihydrobetulinic acid
dc.subjectdocking
dc.subjectmolecular dynamics
dc.titleThe Octahydroindene Carboxyl Substructure from Dihydrobetulinic Acid is Essential to Inhibit Topoisomerase IB from Leishmania donovanien
dc.typeArtigo
dcterms.rightsHolderSoc Brasileira Quimica
unesp.author.orcid0000-0002-8757-321X[3]

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Artigos - Bioquímica e Tecnologia - IQ