TY - JOUR
T1 - In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli
AU - Silva, Lande
AU - Carrion, Lillian Lucas
AU - Groll, Andrea von
AU - Costa, Sofia Santos
AU - Junqueira, Elisabete
AU - Ramos, Daniela Fernandes
AU - Cantos, Jéssica
AU - Seus, Vinicius Rosa
AU - Couto, Isabel
AU - Fernandes, Liana da Silva
AU - Bonacorso, Hélio Gauze
AU - Martins, Marcos Antônio Pinto
AU - Zanatta, Nilo
AU - Viveiros, Miguel
AU - Machado, Karina S.
AU - Almeida da Silva, Pedro Eduardo
PY - 2017/3
Y1 - 2017/3
N2 - 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.
AB - 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.
KW - AcrB
KW - Competition
KW - Efflux
KW - Inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85011878124&partnerID=8YFLogxK
U2 - 10.1016/j.ijantimicag.2016.11.024
DO - 10.1016/j.ijantimicag.2016.11.024
M3 - Article
C2 - 28153476
VL - 49
SP - 308
EP - 314
JO - International Journal Of Antimicrobial Agents
JF - International Journal Of Antimicrobial Agents
SN - 0924-8579
IS - 3
ER -
