Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.creatorGarcia, Danielle Rodrigues-
Autor(es): dc.creatorSouza, Felipe Rodrigues de-
Autor(es): dc.creatorGuimarães, Ana Paula-
Autor(es): dc.creatorRamalho, Teodorico Castro-
Autor(es): dc.creatorAguiar, Alcino Palermo de-
Autor(es): dc.creatorFrança, Tanos Celmar Costa-
Data de aceite: dc.date.accessioned2026-02-09T11:11:32Z-
Data de disponibilização: dc.date.available2026-02-09T11:11:32Z-
Data de envio: dc.date.issued2020-05-14-
Data de envio: dc.date.issued2020-05-14-
Data de envio: dc.date.issued2019-
Fonte completa do material: dc.identifierhttps://repositorio.ufla.br/handle/1/40902-
Fonte completa do material: dc.identifierhttps://www.tandfonline.com/doi/abs/10.1080/07391102.2018.1554510-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1135639-
Descrição: dc.descriptionAcknowledging the importance of studies toward the development of measures against terrorism and bioterrorism, this study aims to contribute to the design of new prototypes of potential drugs against smallpox. Based on a former study, nine synthetic feasible prototypes of selective inhibitors for thymidylate kinase from Variola virus (VarTMPK) were designed and submitted to molecular docking, molecular dynamics simulations and binding energy calculations. The compounds are simplifications of two more complex scaffolds, with a guanine connected to an amide or alcohol through a spacer containing ether and/or amide groups, formerly suggested as promising for the design of selective inhibitors of VarTMPK. Our study showed that, despite the structural simplifications, the compounds presented effective energy values in interactions with VarTMPK and HssTMPK and that the guanine could be replaced by a simpler imidazole ring linked to a –NH2 group, without compromising the affinity for VarTMPK. It was also observed that a positive charge in the imidazole ring is important for the selectivity toward VarTMPK and that an amide group in the spacer does not contribute to selectivity. Finally, prototype 3 was pointed as the most promising to be synthesized and experimentally evaluated.-
Idioma: dc.languageen-
Publicador: dc.publisherTaylor and Francis Online-
Direitos: dc.rightsrestrictAccess-
???dc.source???: dc.sourceJournal of Biomolecular Structure and Dynamics-
Palavras-chave: dc.subjectDrug design-
Palavras-chave: dc.subjectVariola virus-
Palavras-chave: dc.subjectThymidylate kinase-
Palavras-chave: dc.subjectSmallpox-
Palavras-chave: dc.subjectDocking-
Palavras-chave: dc.subjectMolecular dynamics simulations-
Título: dc.titleDesign of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II-
Tipo de arquivo: dc.typeArtigo-
Aparece nas coleções:Repositório Institucional da Universidade Federal de Lavras (RIUFLA)

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