首页|Chemical synthesis, molecular docking and MepA efflux pump inhibitory effect by 1,8-naphthyridines sulfonamides

Chemical synthesis, molecular docking and MepA efflux pump inhibitory effect by 1,8-naphthyridines sulfonamides

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  • NSTL
  • Elsevier
This study aimed to evaluate the antibacterial activity and to verify, in silico and in vitro, the inhibition of efflux mechanisms using a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The chemical synthesis occurred through the thermolysis of the Meldrum?s acid adduct. The sulfonamide derivatives were obtained by the sulfonylation of 2-amino-5-chloro-1,8-naphthyridine with commercial benzenesulfonyl chloride. Antibacterial activity was assessed by the broth microdilution test. Efflux pump inhibitory capacity was evaluated in silico by molecular docking and in vitro by analyzing synergistic effects on ciprofloxacin and ethidium bromide (EtBr) and by EtBr fluorescence emission assays. The following 1,8-naphthyridines were synthesized: 4-methyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfona-mide (Compound 10a); 2,5-dichloro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10b); 4-fluoro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10c); 2,3,4-trifluoro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10d); 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10e); 4-bromo-2,5-difluoro-N-(5-chloro-1,8-naphthyridin-2-yl)-benzene-sulfonamide (Compound 10f). The 1,8-naphthyridines derivatives associated with sulfonamides did not show antibacterial activity. However, they showed a favorable pharmacokinetic profile with possible MepA efflux pump inhibitory action, demonstrated in molecular docking. In addition to the promising results in reducing the concentration of intracellular EtBr. 1,8-naphthyridines act as putative agents in the inhibitory action of the MepA efflux pump.

Antibacterial agentBacterial resistanceEthidium bromideFluorescenceSA-K2068MepA efflux pump

Galvao Rodrigues, Fabiola Fernandes、de Morais Oliveira-Tintino, Cicera Datiane、Tintino, Saulo Relison、Muniz, Debora Feitosa、Rodrigues Teixeira, Alexandre Magno、Barreto, Humberto Medeiros、Alencar de Menezes, Irwin Rose、Melo Coutinho, Henrique Douglas、da Silva, Teresinha Goncalves、Leal Balbino, Tereza Cristina、Martins da Costa, Jose Galberto、dos Santos Barbosa, Cristina Rodrigues、Silva Pereira, Raimundo Luiz、Begnini, Ieda Maria、Rebelo, Ricardo Andrade、da Silva, Luiz Everson、Mireski, Sandro Lucio、Nasato, Michele Caroline、Lacowicz Krautler, Maria Isabel、Pereira, Pedro Silvino

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Reg Univ Cariri, URCA, Dept Biol Chem, Lab Nat Prod, Crato, CE, Brazil

Univ Fed Pernambuco, UFPE, Dept Antibiot, Lab Pharmatoxicol Prospecting Bioact Prod, Recife, PE

Reg Univ Cariri, URCA, Dept Biol Chem, Lab Microbiol & Mol Biol, Crato, CE, Brazil

Reg Univ Cariri, URCA, Dept Biol Chem, Lab Simulat & Mol Spect, Crato, CE, Brazil

Univ Fed Piaui, UFPI, Lab Microbiol, Teresina, PI, Brazil

Reg Univ Cariri, URCA, Dept Biol Chem, Lab Pharmacol & Mol Chem, Crato, CE, Brazil

Fundacao Oswaldo Cruz, Dept Microbiol, Aggeu Magalhaes Res Ctr, CPqAM Fiocruz, UFPE Campus, Recife

Univ Reg Blumenau, Dept Chem, FURB, BR-89030903 Blumenau, SC, Brazil

Univ Fed Parana, Coastal Sect, Postgrad Program Sustainable Terr Dev, Curitiba, Parana, Brazil

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2021

10.1016/j.ejps.2021.105753

European journal of pharmaceutical sciences

European journal of pharmaceutical sciences

ISTP
ISSN：0928-0987
年,卷(期)：2021.160
  • 6
  • 91