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

dc.creatorGarcia, Danielle Rodrigues
dc.creatorSouza, Felipe Rodrigues de
dc.creatorGuimarães, Ana Paula
dc.creatorRamalho, Teodorico Castro
dc.creatorAguiar, Alcino Palermo de
dc.creatorFrança, Tanos Celmar Costa
dc.date2020-05-14T15:37:59Z
dc.date2020-05-14T15:37:59Z
dc.date2019
dc.date.accessioned2023-09-28T19:55:40Z
dc.date.available2023-09-28T19:55:40Z
dc.identifierGARCIA, D. R. et al. Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II. Journal of Biomolecular Structure and Dynamics, [S.l.], v. 37, n. 17, 2019.
dc.identifierhttps://www.tandfonline.com/doi/abs/10.1080/07391102.2018.1554510
dc.identifierhttp://repositorio.ufla.br/jspui/handle/1/40902
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9040355
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.
dc.languageen_US
dc.publisherTaylor and Francis Online
dc.rightsrestrictAccess
dc.sourceJournal of Biomolecular Structure and Dynamics
dc.subjectDrug design
dc.subjectVariola virus
dc.subjectThymidylate kinase
dc.subjectSmallpox
dc.subjectDocking
dc.subjectMolecular dynamics simulations
dc.titleDesign of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II
dc.typeArtigo


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