Inhibition of the NorA efflux pump of S. aureus by (Z)-5-(4-Fluorobenzylidene)-Imidazolidines.

Fluorobenzylidene-imidazolidines were analysed as efflux pump inhibitors against S. aureus SA-1199B, which overproduces the NorA efflux pump. These compounds decreased the Minimum Inhibitory Concentration of norfloxacin and ciprofloxacin up to 6.4- and 3.2-fold, respectively. The experimental and molecular-docking analysis accounts for the mechanism of the inhibition of the efflux pump. • Modulation experiments with EtBr and molecular docking analysis support the inhibition mechanism. • This enhancement activity is mediated by the inhibition of the NorA efflux pump. • The synthetic imidazolines enhanced the activity of norfloxacin and ciprofloxacin against SA-1199B. Searching for new alternatives to antibiotic treatments is crucial to surmount the multidrug-resistant bacteria. In this work, the antimicrobial activity of synthetic imidazolidines was evaluated as well as their modulating effect on the resistance to fluoroquinolones in a S. aureus strain (SA-1199B), which overexpresses the norA gene that encodes the NorA efflux pump. Results showed weak antimicrobial activity (512 μg mL−1) for two fluorobenzylidene derivatives against this bacterial strain, while the other benzylidene derivatives were inactive. Despite this fact, both fluorinated compounds were able to enhance the activity of norfloxacin and ciprofloxacin against SA-1199B up to 6.4– and 3.2-fold, respectively. In addition, both derivatives potentiated the action of ethidium bromide against this strain, suggesting that the modulating effect probably involves the inhibition of the NorA efflux pump, which is in concordance with the fluorimetic assays and molecular docking analyses performed in this work. [ABSTRACT FROM AUTHOR]