Cathepsin K inhibitors based on 2-amino-1,3,4-oxadiazole derivatives

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dc.creatorTalita Bárbara Gontijo
dc.creatorPatrícia da Silva Lima
dc.creatorMarcelo Yudi Icimoto
dc.creatorRaquel Leão Neves
dc.creatorÉrika Lorena Fonseca Costa de Alvarenga
dc.creatorAdriana Karaoglanovic Carmona
dc.creatorAlexandre Alves de Castro
dc.creatorTeodorico de Castro Ramalho
dc.creatorEufrânio Nunes da Silva Júnior
dc.creatorRossimiriam Pereira de Freitas
dc.date.accessioned2024-02-01T18:42:38Z
dc.date.accessioned2025-09-09T01:05:45Z
dc.date.available2024-02-01T18:42:38Z
dc.date.issued2021
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.identifier.doihttps://doi.org/10.1016/j.bioorg.2021.104662
dc.identifier.issn0045-2068
dc.identifier.urihttps://hdl.handle.net/1843/63638
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBioorganic Chemistry
dc.rightsAcesso Restrito
dc.subjectQuímica bioorgânica
dc.subjectInibidores enzimáticos
dc.subjectEnzimas proteolíticas
dc.subjectPeptídios - Síntese
dc.subject.otherCathepsin K
dc.subject.otherDipeptides
dc.subject.other1,3,4-Oxadiazoles
dc.titleCathepsin K inhibitors based on 2-amino-1,3,4-oxadiazole derivatives
dc.typeArtigo de periódico
local.citation.volume109
local.description.resumoTwo new series of hitherto unknown dipeptides, containing an electrophilic nitrile or a non-electrophilic 2-amino-1,3,4-oxadiazole moiety were synthesized and evaluated in vitro as Cathepsin K (Cat K) inhibitors. From 14 compounds obtained, the oxadiazole derivatives 10a, 10b, 10e, and 10g acted as enzymatic competitive inhibitors with Ki values between 2.13 and 7.33 µM. Molecular docking calculations were carried out and demonstrated that all inhibitors performed hydrogen bonds with residues from the enzyme active site, such as Asn18. The best inhibitors (10a, 10b, 10g) could also perform these bonds with Cys25, and 10a showed the most stabilizing interaction energy (−134.36 kcal mol−¹) with the active cavity. For the first time, derivatives based in 2-amino-1,3,4-oxadiazole scaffolds were evaluated, and the results suggested that this core displays a remarkable potential as a building block for Cat K inhibitors.
local.identifier.orcidhttps://orcid.org/0000-0002-7038-8560
local.identifier.orcidhttps://orcid.org/0000-0002-0746-5279
local.identifier.orcidhttps://orcid.org/0000-0002-8898-6032
local.identifier.orcidhttps://orcid.org/0000-0002-9480-9761
local.identifier.orcidhttps://orcid.org/0000-0003-3311-5456
local.identifier.orcidhttps://orcid.org/0000-0003-1806-6270
local.identifier.orcidhttps://orcid.org/0000-0002-7324-1353
local.identifier.orcidhttps://orcid.org/0000-0003-1281-5453
local.identifier.orcidhttps://orcid.org/0000-0001-6974-3724
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0045206821000389

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