Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity

Abstract

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.

A chloride-responsive molecular switch: driving ion transport and empowering antibacterial properties

“…The potent Cl − transporter 1f was tested for its antibacterial activity against Gram-positive and Gram-negative bacterial strains to investigate its biological applicability. 5,26 Compound 1f exhibited strong antibacterial activities against Staphylococcus aureus ( S. aureus ; MIC value of 2.34 ± 0.39 μM) and methicillin-resistant S. aureus (MRSA; MIC value of 2.50 ± 0.50 μM) (Table S2 and Fig. S25–S27†).…”

“…Hence, the development of new approaches or chemical entities for combating infections caused by ESKAPE pathogens is the need of the hour. 2–5…”

“…In this regard, several stimuli-responsive (such as pH, enzyme, redox and light) synthetic ion transporters have been developed to have regulated ion transport properties. 5–11 However, little effort has been made in utilizing biologically active moieties for obtaining stimuli-responsive ion transport properties. This approach would provide compounds with stimuli-responsive antibacterial, anticancer, or other therapeutic activities due to the presence of biologically active moieties and additional ion recognition and transport moieties.…”

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines

“…Quinoline derivatives, known as a class of significant heterocyclic compounds, are frequently found in the application of medicals, ligands, and materials due to their valuable biological and chemical properties. Traditional strategies for the synthesis of these heterocycles, such as Friedlander synthesis and Doebner–von Miller synthesis, , could date back to a long time ago.…”