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metadata.artigo.dc.title: Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox: part II
metadata.artigo.dc.creator: Garcia, Danielle Rodrigues
Souza, Felipe Rodrigues de
Guimarães, Ana Paula
Ramalho, Teodorico Castro
Aguiar, Alcino Palermo de
França, Tanos Celmar Costa
metadata.artigo.dc.subject: Drug design
Variola virus
Thymidylate kinase
Molecular dynamics simulations
metadata.artigo.dc.publisher: Taylor and Francis Online 2019
metadata.artigo.dc.identifier.citation: GARCIA, 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.
metadata.artigo.dc.description.abstract: Acknowledging 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.
metadata.artigo.dc.language: en_US
Appears in Collections:DQI - Artigos publicados em periódicos

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