Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity

The increasing resistance of bacteria to commerciallyavailableantibiotics threatens patient safety in healthcare settings. Perturbationof ion homeostasis has emerged as a potential therapeutic strategyto fight against antibacterial resistance and other channelopathies.This study reports the development of 8-aminoquinoline (QN) derivativesand their transmembrane Zn2+ transport activities. Ourfindings showed that a potent QN-based Zn2+ transporterexhibits promising antibacterial properties against Gram-positivebacteria with reduced hemolytic activity and cytotoxicity to mammaliancells. Furthermore, this combination showed excellent in vivo efficacyagainst Staphylococcus aureus. Interestingly,this combination prevented bacterial resistance and restored susceptibilityof gentamicin and methicillin-resistant S. aureus to commercially available & beta;-lactam and other antibiotics thathad lost their activity against the drug-resistant bacterial strain.Our findings suggest that the transmembrane transport of Zn2+ by QN derivatives could be a promising strategy to combat bacterialinfections and restore the activity of other antibiotics.

Automated summary

This study reports the development of a new 8-aminoquinoline derivative with promising antibacterial activity against Gram-positive bacteria, reduced hemolytic activity and cytotoxicity to mammalian cells. In addition, the combination of this derivative showed excellent efficacy against Staphylococcus aureus and restored the susceptibility of other antibiotics against drug-resistant bacterial strains. The findings suggest that transmembrane zinc ion transport by the derivative could be a promising strategy for combating bacterial infections and restoring antibiotic activity.