Microwave-assisted copper(i) catalyzed A3 cascade coupling of imidazo[1,2-a]pyridines via C–H bond functionalization as selective COX-2 inhibitors and antioxidants, and in silico studies?

New Journal of Chemistry Pub Date: 2023-05-02 DOI: 10.1039/D3NJ00524K

Abstract

A proficient copper(I) catalyzed three-component synthetic protocol has been established for the synthesis of medicinally essential substituted imidazo[1,2-a]pyridines by means of C–H bond amination followed by acetylene incorporation under microwave irradiation. The biological results and computational analysis suggested that the compounds had a greater affinity for the COX-2 enzyme than for the COX-1 enzyme. The investigation of docked (PDB ID: 5IKR; A-chain) postures of the compounds exemplified that they embrace similar configurations to the exceedingly selective COX-2 inhibitor. The compounds 8e, 8h, 8l, 8n, 8p, 8r, 8t, 8v and 8x originated as the most efficient and selective COX-2 inhibitors with IC50 values of 18.94, 0.02, 3.28, 0.067, 0.05, 19.42, 3.66, 0.19 and 24.59 μg mL?1 respectively in contrast to mefenamic acid (25.74 μg mL?1). The selectivity index was obtained for all the significantly active molecules. Excitingly, the molecules that were effective as COX-2 inhibitors were active as antioxidant agents as well.

Graphical abstract: Microwave-assisted copper(i) catalyzed A3 cascade coupling of imidazo[1,2-a]pyridines via C–H bond functionalization as selective COX-2 inhibitors and antioxidants, and in silico studies
Recommended Literature