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

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.