In vivo anti-inflammatory activity and docking study of newly synthesized benzimidazole derivatives bearing oxadiazole and morpholine rings

A series of 18 newer benzimidazole derivatives (5a-r) were synthesized linked with morpholine and oxadiazole rings with the aim to improve the anti-inflammatory and reduce the ulcerogenic effects. The compound 5g showed maximum anti-inflammatory activity of 74.17±1.28 (% Inhibition±SEM) and ulcerogenic activity (SI) of 0.28±0.14 (mean±SEM) and inhibited COX-2 in vitro with IC50 value of 8.1μM. [Display omitted] •A series of novel benzimidazoles was successfully synthesized in good yield.•Docking results are consistent with observed IC50 values.•Compound 5g emerged as most promising candidate as anti-inflammatory agent.•5g can be used as a template for designing potential anti-inflammatory agents. In search of potential therapeutics for inflammatory disease, we report herein the synthesis, characterization and anti-inflammatory activities of a new series of 1-{(5-substituted-1,3,4-oxadiazol-2-yl)methyl}-2-(morpholinomethyl)-1H-benzimidazoles (5a-r). The anti-inflammatory activity of the compounds was evaluated using carrageenan induced rat paw edema test. Some compounds showed excellent anti-inflammatory activity in carrageenan induced rat paw edema test. 1-{(5-(2-Chlorophenyl)-1,3,4-oxadiazol-2-yl)methyl}-2-(morpholinomethyl)-1H-benzimidazole (5g) showed maximum anti-inflammatory (74.17±1.28% inhibition) with reduced ulcerogenic and lipid peroxidation profile and also showed significant COX-2 inhibition with IC50 values of 8.00μM. Compounds 5o and 5q were also found to exhibit good COX-2 inhibition with IC50 values of 11.4 and 13.7μM concentrations. Molecular docking study showed that morpholine and oxadiazole rings linked to the benzimidazole nucleus play an important role in binding with the COX-2.