Multicomponent reaction for synthesis, molecular docking, and anti-inflammatory evaluation of novel indole-thiazole hybrid derivatives.

In this article, novel thiazol-indolin-2-one derivatives 4a-f have been synthesized via treatment of thiosemicarbazide (1) with some isatin derivative 2a-f and N-(4-(2-bromoacetyl)phenyl)-4-tolyl-sulfonamide (3) under reflux in ethanol in the presence of triethyl amine (TEA). The structures of new products were elucidated by elemental and spectral analyses. Moreover, all compounds were investigated for their in vivo anti-inflammatory activity using celecoxib as a reference drug. The target compound 4b was the most active anti-inflammatory candidate and exhibited higher edema inhibition (EI = 38.50%) than that recorded by celecoxib (EI = 34.58%) after 3 h. Furthermore, the most active compounds 4b and 4f were subjected to a molecular docking study inside COX-2 enzyme to show their binding interactions. Both compounds 4b and 4f showed good fitting into COX-2 binding site with docking energy scores - 11.45 kcal/mol and - 10.48 kcal/mol, respectively which indicated that compound 4b revealed the most promising and effective anti-inflammatory potential.