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THE 1,8-NAPHTHYRIDINES SULFONAMIDES ARE NORA EFFLUX PUMP INHIBITORS
Oliveira-Tintino, Cícera Datiane de Morais et al. | Fecha del documento: 2021
Autor
Oliveira-Tintino, Cícera Datiane de Morais
Muniz, Débora Feitosa
Barbosa, Cristina Rodrigues dos Santos
Pereira, Raimundo Luiz Silva
Begnini, Iêda Maria
Rebelo, Ricardo Andrade
Silva, Luiz Everson da
Mireski, Sandro Lucio
Nasato, Michele Caroline
Krautler, Maria Isabel Lacowicz
Pereira, Pedro Silvino
Costa, José Galberto Martins da
Rodrigues, Fabiola Fernandes Galvão
Teixeira, Alexandre Magno Rodrigues
Ribeiro-Filho, Jaime
Tintino, Saulo Relison
Menezes, Irwin Rose Alencar de
Coutinho, Henrique Douglas Melo
Silva, Teresinha Gonçalves da
Afiliación
Federal University of Pernambuco. Department of Antibiotics. Laboratory of Pharmatoxicological Prospecting of Bioactive Products. Recife, PE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Microbiology and Molecular Biology. Crato, CE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Microbiology and Molecular Biology. Crato, CE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Microbiology and Molecular Biology. Crato, CE, Brazil.
Regional University of Blumenau. Department of Chemistry. Blumenau, SC, Brazil.
Regional University of Blumenau. Department of Chemistry. Blumenau, SC, Brazil.
Federal University of Paraná. Coastal Sector. Postgraduate Program in Sustainable Territorial Development. Curitiba, PR, Brazil.
Regional University of Blumenau. Department of Chemistry. Blumenau, SC, Brazil.
Regional University of Blumenau. Department of Chemistry. Blumenau, SC, Brazil.
Regional University of Blumenau. Department of Chemistry. Blumenau, SC, Brazil.
Federal University of Pernambuco. Department of Antibiotics. Laboratory of Pharmatoxicological Prospecting of Bioactive Products; Recife, PE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Natural Products. Crato, CE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Natural Products. Crato, CE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of simulations and molecular spectroscopy. Crato, CE, Brazil.
Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Microbiology and Molecular Biology. Crato, CE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Pharmacology and Molecular Chemistry. Crato, CE, Brazil.
Regional University of Cariri. Department of Biological Chemistry. Laboratory of Microbiology and Molecular Biology. Crato, CE, Brazil.
Federal University of Pernambuco. Department of Antibiotics. Laboratory of Pharmatoxicological Prospecting of Bioactive Products. Recife, PE, Brazil.
Resumen en ingles
Objective: Efflux pumps are transmembrane proteins associated with bacterial resistance mechanisms. Bacteria use these proteins to actively transport antibiotics to the extracellular medium, preventing the pharmacological action of these drugs. This study aimed to evaluate in vitro the antibacterial activity of 1,8-naphthyridines sulfonamides, as well as their ability to inhibit efflux systems of Staphylococcus aureus strains expressing different levels of the NorA efflux pump. Methods: The broth microdilution test was performed to assess antibacterial activity. Efflux pump inhibition was evaluated in silico by molecular docking and in vitro by fluorometric tests, and the minimum inhibitory concentration (MIC) was determined. The MIC was determined in the association between 1,8-naphthyridine and norfloxacin or ethidium bromide. Results: The 1,8-naphthyridines did not show direct antibacterial activity. However, they effectively reduced the MIC of multidrug-resistant bacteria by associating with norfloxacin and ethidium bromide, in addition to increasing the fluorescence emission. In silico analysis addressing the binding between NorA and 1,8-naphthyridines suggests that hydrogen bonds and hydrophilic interactions represent the interactions with the most favourable binding energy, corroborating the experimental data. Conclusion: Our data suggest that 1,8-naphthyridines sulfonamides inhibit bacterial resistance through molecular mechanisms associated with inhibition of the NorA efflux pump in S. aureus strains.
Palabras clave en ingles
Antibacterial agents
Ethidium bromide fluorescence
Molecular docking
NorA efflux pump
Naphthyridines
 
Editor
Elsevier
Referencia
OLIVEIRA-TINTINO, Cícera Datiane de Morais et al. The 1,8-naphthyridines sulfonamides are NorA efflux pump inhibitors. Journal of Global Antimicrobial Resistance, v. 24, p. 233-240, Mar. 2021.
DOI
10.1016/j.jgar.2020.11.027
ISSN
2213-7165