Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity

The increasing resistance of bacteria to commercially
available
antibiotics threatens patient safety in healthcare settings. Perturbation
of ion homeostasis has emerged as a potential therapeutic strategy
to fight against antibacterial resistance and other channelopathies.
This study reports the development of 8-aminoquinoline (QN) derivatives
and their transmembrane Zn2+ transport activities. Our
findings showed that a potent QN-based Zn2+ transporter
exhibits promising antibacterial properties against Gram-positive
bacteria with reduced hemolytic activity and cytotoxicity to mammalian
cells. Furthermore, this combination showed excellent in vivo efficacy
against Staphylococcus aureus. Interestingly,
this combination prevented bacterial resistance and restored susceptibility
of gentamicin and methicillin-resistant S. aureus to commercially available β-lactam and other antibiotics that
had 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 bacterial
infections and restore the activity of other antibiotics.