In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli

Lande Silva, Lillian Lucas Carrion, Andrea von Groll, Sofia Santos Costa, Elisabete Junqueira, Daniela Fernandes Ramos, Jéssica Cantos, Vinicius Rosa Seus, Isabel Couto, Liana da Silva Fernandes, Hélio Gauze Bonacorso, Marcos Antônio Pinto Martins, Nilo Zanatta, Miguel Viveiros, Karina S. Machado, Pedro Eduardo Almeida da Silva

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12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)308-314
Number of pages7
JournalInternational Journal Of Antimicrobial Agents
Volume49
Issue number3
DOIs
Publication statusPublished - Mar 2017

Keywords

  • AcrB
  • Competition
  • Efflux
  • Inhibitors

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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