2.B.112.  The Quinoline Thiourea-based Zinc Ionophore (QT-ZnI) Family 

Perturbation of ion homeostasis is a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. Dey et al. 2023 reported the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn2+ transport activities. Potent QN-based Zn2+ transporters exhibit antibacterial properties against Gram-positive bacteria with reduced hemolytic activity and cytotoxicity to mammalian cells. They showed in vivo efficacy against Staphylococcus aureus, prevented bacterial resistance, and restored susceptibility of gentamicin and methicillin-resistant S. aureus to commercially available beta-lactams and other antibiotics that had lost their activity against the drug-resistant bacterial strain (Dey et al. 2023). Several QN derivatives were tested for Zn2+ transport activity, and several proved effective.  The mechanism may involve Zn2+:H+ antiport.


 

References:

Dey, S., A. Patel, N. Haloi, S. Srimayee, S. Paul, G.K. Barik, N. Akhtar, D. Shaw, G. Hazarika, B.M. Prusty, M. Kumar, M.K. Santra, E. Tajkhorshid, S. Bhattacharjee, and D. Manna. (2023). Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity. J Med Chem. [Epub: Ahead of Print]