Design, Synthesis, and Antimicrobial Evaluation of Quinolones Containing 1,2,3-Triazole Moieties: In Silico Docking Techniques

Abstract

Objective: We have been studying the synthesis and biological activity of compounds that simultaneously comprise different heterocycles, like 1,2,3-triazoles and fused 2-quinolones, as part of our ongoing research in organic and medicinal chemistry. Methods: Using 6-methoxy-1-methyl-4-(prop-2-yn-1-yloxy)quinolin-2(1H)-one and various aryl azides, we developed and synthesized a number of novel quinolones linked 1,2,3-triazoles. The structures of the newly synthesized derivatives are characterized from IR, ¹H NMR, ¹³C NMR, and mass analysis. The prepared derivatives were screened their in vitro antibacterial activity against S. Epidermidis, S. aureus, S. Pneumonia, P. Aeruginosa and antifungal activity against A. niger and C. albicans. Results and Discussions: Among all the synthesized compounds, 6-methoxy-1-methyl-4-((1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)methoxy)quinolin-2(1H)-one have shown potent antibacterial activity against S. Epidermidis, S. aureus, and S. Pneumonia as compared to standard Moxifloxacin with MIC values 2.38 ± 0.01, 3.32 ± 0.04, and 2.52 ± 0.01 µg/mL. Similarly, antifungal activity of newly synthesized derivatives same compound has shown more potent activity against A. niger and C. albicans fungal strains with MIC values 2.67 ± 0.01 and 2.70 ± 0.01 µg/mL. In silico molecular docking results of more potent compounds were shown comparable binding energies. Finally, the in silico pharmacokinetic profile of all the synthesized derivatives were estimated using SwissADME and pkCSM, where all some of the compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation. Conclusions: The focus of this research is on recent advances in drug design and development, as well as quinolone-triazole derivatives and how they work on antibacterial and antifungal sites of action.