In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli.
Int J Antimicrob Agents
; 49(3): 308-314, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-28153476
ABSTRACT
The objectives of this study were to evaluate tetrahydropyridine derivatives as efflux inhibitors and to understand the mechanism of action of the compounds by in silico studies. Minimum inhibitory concentration (MIC) determination, fluorometric methods and docking simulations were performed. The compounds NUNL02, NUNL09 and NUNL10 inhibited efflux, and NUNL02 is very likely a substrate of the transporter protein AcrB. Docking studies suggested that the mechanism of action could be by competition with substrate for binding sites and protein residues. We showed for the first time the potential of tetrahydropyridines as efflux inhibitors and highlighted compound NUNL02 as an AcrB-specific inhibitor. Docking studies suggested that competition is the putative mechanism of action of these compounds.
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MEDLINE
Assunto principal:
Piridinas
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Transporte Biológico Ativo
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Proteínas de Escherichia coli
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Inibidores Enzimáticos
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Escherichia coli
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Antibacterianos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article