Hybrid 2-Quinolone-1,2,3-triazole Compounds: Rational Design, In Silico Optimization, Synthesis, Characterization, and Antibacterial Evaluation.

Abstract

Background/Objectives: The rise in antibiotic resistance presents a serious and urgent global health challenge, emphasizing the need to develop new therapeutic compounds. This study focuses on the design and evaluation of a novel series of hybrid molecules that combine the 2-quinolone and 1,2,3-triazole pharmacophores, both recognized for their broad-spectrum antimicrobial properties. Methods: A library of 29 candidate molecules was first designed using in silico techniques, including QSAR modeling, ADMET prediction, molecular docking, and molecular dynamics simulations, to optimize antibacterial activity and drug-like properties. The most promising compounds were then synthesized and characterized by ¹H and ¹³C NMR APT, mass spectrometry (MS), Fourier-transform infrared (FT-IR) spectroscopy, and UV-Vis spectroscopy. Results: Antibacterial evaluation revealed potent activity against both Gram-positive and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values ranging from 0.019 to 1.25 mg/mL. Conclusions: These findings demonstrate the strong potential of 2-quinolone-triazole hybrids as effective antibacterial agents and provide a solid foundation for the development of next-generation antibiotics to combat the growing threat of bacterial resistance.