Chloroxine

Chloroxine is a dihalogenated 8-hydroxyquinoline compound that exhibits antibacterial activity through multiple mechanisms. The compound effectively inhibits the enzymatic activity of superoxide dismutase (SOD), a key antioxidant enzyme in bacterial cells. This SOD inhibition disrupts the bacterial oxidative stress defense system, leading to increased susceptibility to oxidative damage. Chloroxine demonstrates increased antibacterial potency against Gram-positive bacteria compared to Gram-negative bacteria. The introduction of exogenous manganese or zinc ions significantly boosts chloroxine's antibacterial efficacy against Gram-negative bacteria, including ESKAPE pathogens such as Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. The enhanced antibacterial activity induced by zinc ions involves the proton motive force and oxidative and antioxidative systems, as the effect can be negated in the presence of copper or ferrous iron ions or by changes in oxygen availability. Additionally, chloroxine can reverse polymyxin and carbapenem resistance in Escherichia coli in vitro.

Fig. 1 Mechanisms of Chloroxine's antibacterial activity. (Huang X.; et al. 2024)