Discovery of novel halogenated 8‐hydroxyquinoline‐based anti‐MRSA agents: In vitro and QSAR studies

Abstract Methicillin‐resistant Staphylococcus aureus (MRSA) infection has been considered to be one of global health problems due to limited classes of effective antimicrobial drugs. Herein, 8‐hydroxyquinoline (8HQ) and its derivatives ( 1‐7 ) were investigated for their anti‐MRSA and antioxidant activities. Cloxyquin ( 2 ), a halogenated 8HQ, exerted the highest antimicrobial activity (MIC 50 ≤ 5.57 μM) with high safety index, whereas an amino‐derivative 7 showed the strongest antioxidant activity. Additionally, quantitative structure‐activity relationship (QSAR) study demonstrated that mass, polarizability, topological charge, and van der Waals volume are essential properties governing the anti‐MRSA activity. Taken together, cloxyquin was highlighted as a promising compound for further development as a novel anti‐MRSA agent. QSAR findings would also benefit for further rational design of novel 8HQ‐based compounds to combat the MRSA resistance.