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Use este identificador para citar o ir al link de este elemento: http://hdl.handle.net/1843/77842
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Campo DCValorIdioma
dc.creatorPriscila Goes Carvalhopt_BR
dc.creatorMarciéli Fabrispt_BR
dc.creatorMatheus Yoshimitsu Tatsuta Nakamaept_BR
dc.creatorBreno Germano de Freitas Oliveirapt_BR
dc.creatorCamilo Henrique da Silva Limapt_BR
dc.creatorÂngelo de Fátimapt_BR
dc.creatorMarcelle de Lima Ferreira Bispopt_BR
dc.creatorFernando Cesar Macedo Juniorpt_BR
dc.date.accessioned2024-11-05T23:00:21Z-
dc.date.available2024-11-05T23:00:21Z-
dc.date.issued2022-
dc.citation.volume365pt_BR
dc.citation.spage110045pt_BR
dc.identifier.doihttps://doi.org/10.1016/j.cbi.2022.110045pt_BR
dc.identifier.issn0009-2797pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/77842-
dc.description.resumoWe report the investigation of hydantoins and thiohydantoins derived from L and d-amino acids as inhibitors against the Canavalia ensiformis urease (CEU). The biochemical in vitro assay against CEU revealed a promising inhibitory potential for most thiohydantoins with six of them showing %I higher than the reference inhibitor thiourea (56.5%). In addition, thiohydantoin derived from l-valine, 1b, as well as the hydantoin 2d, derived from l-methionine, were identified as the most potent inhibitors with %I = 90.5 and 85.9 respectively. Enzyme kinetic studies demonstrated a mixed and uncompetitive inhibition profile for these compounds with Ki values of 0.42 mM for 1b and 0.99 mM for 2d. These kinetic parameters, obtained from traditional colorimetric assay, were strictly related to the KD values measured spectroscopically by the Saturation Transfer Difference (STD) technique for the urease complex. STD was also used to evince the moieties of the ligands responsible for the binding with the enzyme. Molecular docking studies showed that the thiohydantoin and hydantoin rings can act as a pharmacophoric group due to their binding affinity by hydrogen bonding interactions with critical amino acid residues in the enzyme active and/or allosteric site. These findings agreed with the experimental alpha values, demonstrating that 1b has affinity by free enzyme, and 2d derivative, an uncompetitive inhibitor, has great binding affinity at the allosteric site. The results for the thiohydantoin 1a, derived from d-valine, demonstrated a drastic stereochemical influence on inhibition, kinetics, and binding parameters in comparison to its enantiomer 1b.pt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Geraispt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentICX - DEPARTAMENTO DE QUÍMICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofChemico-Biological Interactionspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectThiohydantoinspt_BR
dc.subjectHydantoinspt_BR
dc.subjectNMRpt_BR
dc.subjectMolecular dockingpt_BR
dc.subjectC. ensiformispt_BR
dc.subjectSaturation Transfer Difference STDpt_BR
dc.subject.otherRessonância magnética nuclearpt_BR
dc.subject.otherCanavalia ensiformispt_BR
dc.subject.otherUrease - Inibidorespt_BR
dc.subject.otherEstereoquimicapt_BR
dc.titleThiohydantoins and hydantoins derived from amino acids as potent urease inhibitors: inhibitory activity and ligand-target interactionspt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.sciencedirect.com/science/article/pii/S0009279722002502pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-4483-2119pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0001-6763-3046pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-4631-389Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-5579-7809pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-2344-5590pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-6001-360Xpt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-4230-1309pt_BR
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