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

doi:10.1016/j.ijantimicag.2016.11.024

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 language	English
Pages (from-to)	308-314
Number of pages	7
Journal	International Journal Of Antimicrobial Agents
Volume	49
Issue number	3
DOIs	https://doi.org/10.1016/j.ijantimicag.2016.11.024
Publication status	Published - Mar 2017

Keywords

AcrB
Competition
Efflux
Inhibitors

UN Sustainable Development Goals (SDGs)

SDG 3 - Good Health and Well-Being

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10.1016/j.ijantimicag.2016.11.024

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Silva, L., Carrion, L. L., Groll, A. V., Costa, S. S., Junqueira, E., Ramos, D. F., Cantos, J., Seus, V. R., Couto, I., Fernandes, L. D. S., Bonacorso, H. G., Martins, M. A. P., Zanatta, N., Viveiros, M., Machado, K. S., & Almeida da Silva, P. E. (2017). In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli. International Journal Of Antimicrobial Agents, 49(3), 308-314. https://doi.org/10.1016/j.ijantimicag.2016.11.024

Silva, Lande ; Carrion, Lillian Lucas ; Groll, Andrea von ; Costa, Sofia Santos ; Junqueira, Elisabete ; Ramos, Daniela Fernandes ; Cantos, Jéssica ; Seus, Vinicius Rosa ; Couto, Isabel ; Fernandes, Liana da Silva ; Bonacorso, Hélio Gauze ; Martins, Marcos Antônio Pinto ; Zanatta, Nilo ; Viveiros, Miguel ; Machado, Karina S. ; Almeida da Silva, Pedro Eduardo. / In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli. In: International Journal Of Antimicrobial Agents. 2017 ; Vol. 49, No. 3. pp. 308-314.

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

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.",

keywords = "AcrB, Competition, Efflux, Inhibitors",

author = "Lande Silva and Carrion, {Lillian Lucas} and Groll, {Andrea von} and Costa, {Sofia Santos} and Elisabete Junqueira and Ramos, {Daniela Fernandes} and J{\'e}ssica Cantos and Seus, {Vinicius Rosa} and Isabel Couto and Fernandes, {Liana da Silva} and Bonacorso, {H{\'e}lio Gauze} and Martins, {Marcos Ant{\^o}nio Pinto} and Nilo Zanatta and Miguel Viveiros and Machado, {Karina S.} and {Almeida da Silva}, {Pedro Eduardo}",

year = "2017",

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doi = "10.1016/j.ijantimicag.2016.11.024",

language = "English",

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Silva, L, Carrion, LL, Groll, AV, Costa, SS, Junqueira, E, Ramos, DF, Cantos, J, Seus, VR, Couto, I, Fernandes, LDS, Bonacorso, HG, Martins, MAP, Zanatta, N, Viveiros, M, Machado, KS & Almeida da Silva, PE 2017, 'In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli', International Journal Of Antimicrobial Agents, vol. 49, no. 3, pp. 308-314. https://doi.org/10.1016/j.ijantimicag.2016.11.024

In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli. / Silva, Lande; Carrion, Lillian Lucas; Groll, Andrea von; Costa, Sofia Santos; Junqueira, Elisabete; Ramos, Daniela Fernandes; Cantos, Jéssica; Seus, Vinicius Rosa; Couto, Isabel; Fernandes, Liana da Silva; Bonacorso, Hélio Gauze; Martins, Marcos Antônio Pinto; Zanatta, Nilo; Viveiros, Miguel; Machado, Karina S.; Almeida da Silva, Pedro Eduardo.

In: International Journal Of Antimicrobial Agents, Vol. 49, No. 3, 03.2017, p. 308-314.

Research output: Contribution to journal › Article

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

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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 -