In silico evaluation of the antibacterial and modulatory activity of lapachol and nor-lapachol derivates.

Autor: Figueredo FG; Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Ceará - UFC, CEP 60.430-370, Fortaleza, CE, Brazil; Department of Microbiology, Faculdade de Medicina Estácio de Juazeiro Do Norte, CEP 63048-080, Juazeiro Do Norte, CE, Brazil. Electronic address: fgfigueredo@gmail.com., Ramos ITL; Department of Chemistry, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil. Electronic address: ingridtrajano93@gmail.com., Paz JA; Department of Chemistry, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil., Silva TMS; Department of Chemistry, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil. Electronic address: sarmentosilva@gmail.com., Camara CA; Department of Chemistry, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil. Electronic address: ccelso@gmail.com., Oliveira-Tintino CDM; Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., Relison Tintino S; Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., de Farias PAM; Department of Microbiology, Faculdade de Medicina Estácio de Juazeiro Do Norte, CEP 63048-080, Juazeiro Do Norte, CE, Brazil., Coutinho HDM; Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil. Electronic address: hdmcoutinho@urca.br., Fonteles MMF; Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Ceará - UFC, CEP 60.430-370, Fortaleza, CE, Brazil.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2020 Jul; Vol. 144, pp. 104181. Date of Electronic Publication: 2020 Apr 08.
DOI: 10.1016/j.micpath.2020.104181
Abstrakt: The aim of this research was to investigate the pharmacological properties of 2-(2-hydroxyethylamine)-3-(3-methyl-2-butenyl)-1,4-dihydro-1,4-naphthalenedione, 2-(2-hydroxy-ethylamine)-3-(2-methyl-propenyl)-[1,4]naphthoquinone and 2-(3-hydroxy-propylamine)-3-(3-methyl-2-butenyl)-[1,4]naphthoquinone using computational prediction models, in addition to evaluating the in vitro antibacterial and modulatory activity of these compounds against bacterial ATCC strains and clinical isolates. The substances were synthesized from 2-hydroxy-quinones, lapachol and nor-lapachol obtaining the corresponding 2-methoxylated derivatives via dimethyl sulfate alkylation in a basic medium, these then reacted chemoselectively with 2-ethanolamine and 3-propanolamine to form the corresponding amino alcohols. The antibacterial activity and modulatory activity of the substances were assayed by broth microdilution method to determine the Minimum Inhibitory Concentration (MIC). The molecular structures were analyzed using the ChEMBL database to predict possible pharmacological targets, which pointed to the molecule 2- (2-hydroxy-ethylamine)-3-(2-methyl-propenyl)-[1,4]naphthoquinone as a probable antibacterial agent for the proteins Replicative DNA helicase and RecA. The compounds had a low molecular weight and a small number of rotatable bonds. The MICs of the substances were not clinically significant, however, the association with gentamicin and amikacin reduced the MICs of these antibiotics. In conclusion, the combination of these substances with aminoglycosides may be a therapeutic alternative to bacterial resistance and the reduction of side effects.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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