Design and Synthesis of Novel Indolizine Analogues as COX-2 Inhibitors: Computational Perspective and in vitro Screening

Design and synthesis of a new series of ethyl 7-methoxy-2-substituted-3-(substituted benzoyl) indolizine-1-carboxylates 2a-i was achieved and screened for their in vitro inhibitory activity against COX-2 enzyme. Compound 2a and 2c emerged as promising COX-2 enzyme inhibitor with IC50 of 6.56 and 6.94 mu M respectively from the synthesized series when compared to Celecoxib and Indomethacin as selective and nonselective standards, respectively. Computational docking study identified the possible reasons for such activity that may be due to the cis configuration of the indolizines that resulted in the most stable conformation similar to that of Indomethacin.