Nitroxoline: a potent antimicrobial agent against multidrug resistant Enterobacteriaceae

Antimicrobial resistance has become a prime global concern. An ability of the microbes to produce enzymes to destroy antimicrobial drugs is one of the well-known mechanisms underlying the resistance. 8-Hydroxyquinoline (8HQ) and derivatives were reported to exert diverse biological effects such as antimicrobial, antioxidant and antineurodegenerative activities. Herein, 8HQ (1), nitroxoline (NQ, 2) and 7-Br-8HQ (3) were investigated for antimicrobial activity against Enterobacteriaceae including extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing strains as well as the effect of metal ions. These compounds (1-3) displayed the great antimicrobial activity against fifty-eight bacterial isolates of Escherichia coli, Providencia rettgeri and Klebsiella pneumoniae, in which NQ (2) exerted the highest antimicrobial activity with a MIC₅₀ of 42.04 μM (8 µg/mL) and MBC₅₀ of 168.28 μM (32 µg/mL). The MIC values of NQ (2) and 7-Br-8HQ (3) were significantly increased in the presence of Cu^{2 +} and Fe³⁺. This finding reveals that NQ could be an effective compound to be further developed as an antimicrobial agent for combating Enterobacteriaceae infections.