Synthesis and antibacterial evaluation of quinoline–sulfonamide hybrid compounds: a promising strategy against bacterial resistance

Abstract

Antibiotic-resistant bacteria are a serious global health threat, making infections harder to treat and increasing medical costs and mortality rates. To combat resistant bacterial strains, a series of compounds (QS1–12) were synthesized with an excellent yield of 85–92%. Initial assessments of these analogues as potential antibacterial agents were conducted through a preliminary screening against a panel of diverse bacterial strains. The results identified compound QS-3 as the most effective antibacterial candidate, exhibiting exceptional inhibitory activity against P. aeruginosa with a minimum inhibitory concentration (MIC) of 64 μg mL⁻¹. Furthermore, QS-3 demonstrated a favorable synergistic effect when combined with ciprofloxacin. Notably, the compound displayed minimal cytotoxicity, inducing less than 5% lysis of red blood cells (RBCs). Significantly, QS-3 exhibited enhanced inhibitory activity, particularly against the antibiotic-resistant strains AA202 and AA290. In silico predictions of physicochemical properties underscored the drug-like qualities of the designed compounds. Additionally, molecular docking poses, ligPlot images, and a binding affinity of −8.0 kcal mol⁻¹ further reinforced their potential as promising antibacterial agents. Briefly, the reported compound QS3 may be a future broad-range antibacterial agent.