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https://www.arca.fiocruz.br/handle/icict/43616
IN VITRO AND IN SILICO INHIBITORY EFFECTS OF SYNTHETIC AND NATURAL EUGENOL DERIVATIVES AGAINST THE NORA EFFLUX PUMP IN STAPHYLOCOCCUS AUREUS
Author
Muniz, Débora Feitosa
Barbosa, Cristina Rodrigues dos Santos
Menezes, Irwin Rose Alencar de
Sousa, Erlânio Oliveira de
Pereira, Raimundo Luiz Silva
Calixto Júnior, João Tavares
Pereira, Pedro Silvino
Matos, Yedda M.L.S. de
Costa, Roger H.S. da
Tintino, Cícera Datiane de Morais Oliveira
Coutinho, Henrique Douglas Melo
Barbosa Filho, José Maria
Sousa, Gabriela Ribeiro de
Ribeiro Filho, Jaime
Siqueira Junior, José Pinto
Tintino, Saulo Relison
Barbosa, Cristina Rodrigues dos Santos
Menezes, Irwin Rose Alencar de
Sousa, Erlânio Oliveira de
Pereira, Raimundo Luiz Silva
Calixto Júnior, João Tavares
Pereira, Pedro Silvino
Matos, Yedda M.L.S. de
Costa, Roger H.S. da
Tintino, Cícera Datiane de Morais Oliveira
Coutinho, Henrique Douglas Melo
Barbosa Filho, José Maria
Sousa, Gabriela Ribeiro de
Ribeiro Filho, Jaime
Siqueira Junior, José Pinto
Tintino, Saulo Relison
Affilliation
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Regional University of Cariri. Laboratory of Studies of the Regional Flora of the Cariri. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
University of João Pessoa. Laboratory of Phamaceutical Tecnology Federal. João Pessoa, PB, Brazil.
University of João Pessoa. Laboratory of Phamaceutical Tecnology Federal. João Pessoa, PB, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Regional University of Cariri. Laboratory of Studies of the Regional Flora of the Cariri. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Pharmacology and Molecular Chemistry. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
University of João Pessoa. Laboratory of Phamaceutical Tecnology Federal. João Pessoa, PB, Brazil.
University of João Pessoa. Laboratory of Phamaceutical Tecnology Federal. João Pessoa, PB, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Universidade Regional do Cariri. Laboratory of Microbiology and Molecular Biolog y. Department of Biological Chemistry. Cariri, CE, Brazil.
Abstract
Staphylococcus aureus is a Gram-positive bacterium responsible for a number of diseases and has demonstrated
resistance to conventional antibiotics. This study aimed to evaluate the antibacterial activity of eugenol and its
derivatives allylbenzene, 4-allylanisole, isoeugenol and 4-allyl-2,6-dimethoxyphenol against the S. aureus NorA
efflux pump (EP) in association with norfloxacin and ethidium bromide. The antibacterial activity of the compounds
was assessed using the broth microdilution method to determine the minimum inhibitory concentration
(MIC). A reduction in the MIC of ethidium bromide (a substrate for several efflux pumps) or norfloxacin was used
as a parameter of EP inhibition. Molecular modeling studies were used to predict the 3D structure and analyze
the interaction of selected compounds with the binding pocket of the NorA efflux pump. Except for 4-allylanisole
and allylbenzene, the compounds presented clinically effective antibacterial activity. When associated with
norfloxacin against the SA 1199B strain, 4-allyl-2,6-dimethoxyphenol eugenol and isoeugenol caused significant
reduction in the MIC of the antibiotic, demonstrating synergistic effects. Similar effects were observed when 4-
allyl-2,6-dimethoxyphenol, allylbenzene and isoeugenol were associated with ethidium bromide. Together, these
findings indicate a potential inhibition of the NorA pump by eugenol and its derivatives. This in vitro evidence
was corroborated by docking results demonstrating favorable interactions between 4-allyl-2,6-dimetoxypheno
and the NorA pump mediated by hydrogen bonds and hydrophobic interactions. In conclusion, eugenol derivatives
have the potential to be used in antibacterial drug development in strains carrying the NorA efflux pump.
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