Aim: The undeniable indomethacin potency has always suffered serious obstacles such as gastric damage. Continuous attempts to develop potent yet safe indomethacin analogs have never ceased. Results: Herein are new indole derivatives 4a-h and 5a-c, which were synthesized via Fisher indole reaction, evaluated for both their in vivo anti-inflammatory activities using rat paw edema method and their in vitro cyclooxygenase inhibitory activities. Then ulcerogenic liability, physicochemical parameters and molecular docking modeling were performed for the most potent ones. Conclusion: Promising results were obtained, where compound 4f was the best anti-inflammatory agent and preferential COX-2/COX-1 inhibitor (90.5% edema inhibition, selective index = 65.71, ulcer index = 7.3), if compared with indomethacin (86.7% edema inhibition, selective index = 0.079, ulcer index = 20.20).
Keywords: Lipinski; anti-inflammatory; celecoxib; cyclooxygenase; docking; indole; indomethacin; molecular; ulcer.