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

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 mu g 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.

Automated summary

Two fluorobenzylidene derivatives showed weak antimicrobial activity against a Staphylococcus aureus strain but significantly enhanced the effectiveness of norfloxacin and ciprofloxacin. The modulation effect of these compounds may involve inhibiting the NorA efflux pump.