3-Aryl-4-methyl-2-quinolones Targeting Multiresistant Staphylococcus aureus Bacteria

The NorA efflux pump lowers intracellular fluoroquinolone concentrations by expelling antibiotics through the membrane of Staphylococcus aureus. We identified 3‐aryl‐4‐methyl‐2‐quinolin‐2‐ones as compounds able to restore the activity of the NorA substrate, ciprofloxacin, against resistant S. aureus strains, and acting as efflux pump inhibitors (EPI). In particular, 5‐hydroxy‐7‐methoxy‐4‐methyl‐3‐phenylquinolin‐2‐one (6 c) presents both an EPI and an antimicrobial effect. Its efficacy and safety make it a potential candidate for further investigations. Stop the resistance! 3‐Aryl‐4‐methyl‐2‐quinolones are NorA efflux pump inhibitors that are able to restore the sensitivity of resistant Staphylococcus aureus bacteria toward fluoroquinolones. The most active compound is nontoxic, can be easily prepared in two steps, and shows intrinsic antibacterial activity.