Novel 4-(1H-1,2,3-triazol-4-yl)methoxy)cinnolines as potent antibacterial agents: Synthesis and molecular docking study

Abstract

A new series of cinnoline-1,2,3-triazole derivatives were designed and synthesized by adopting Cu(1) catalyzed regeoselective1,3-dipolar cycloaddition reaction of terminal alkyne and azide. The in vitro antibacterial activity of all these compounds revealed that compounds 9d, 10a, 10b, and 10c are more potent antibacterial agents. Among the series, compound 4-(3-(4-((cinnolin-4-yloxy)methyl)-1H-1,2,3-triazol-1-yl)propyl)morpholine (10b) exhibited the most potent antibacterial activity against all tested gram-positive and gram-negative bacterial strains. Furthermore, molecular docking studies were also performed to understand the binding interactions of the most active analogs 9d, 10a, 10b, and 10c with Elastase of Pseudomonas aeruginosa (PDB: 1U4G). The results indicated that these classes of compounds have potential antibacterial activity, especially the compound 10b may serve as a promising antibacterial lead compound that could be further optimized for the further development of antibacterial drugs.

Graphical Abstract

Keywords:

• Anti-bacterial activity
• cinnolines
• click reaction
• molecular docking studies
• triazoles

Acknowledgments

Authors, Mohan Babu thanks to, Head Department of Chemistry, CFRD Osmania University, Hyderabad, Telangana, India for providing facilities.