DESIGN, SYNTHESIS, IN VITRO ANTIOXIDANT AND IN VIVO ANTI-INFLAMMATORY ACTIVITIES OF NOVEL OXADIAZOLE DERIVATIVES
Objective: In the present study, a series of novel 1,3,4-oxadiazole derivatives (3a-3q) were designed, synthesized and evaluated for antioxidant and anti-inflammatory activities.
Methods: The title compounds were designed and docked onto the COX-2 enzyme (3LN1) protein using SYBYLX 2.1. 2-substituted-5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole derivatives (3a-3p) were synthesized from acid catalyzed dehydrative cyclization of 5-nitrobenzofuran-2-carbohydrazide (2) with various heteroaryl/aryl/aliphatic carboxylic acid derivatives. And 5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole-2-thiol (3q) was synthesized on reacting the hydrazide derivative 2 with carbon disulfide. The synthesized compounds were evaluated for in vitro antioxidant property by DPPH radical scavenging assay method and in vivo anti-inflammatory activity by carrageenan induced paw edema method.
Results: The synthesized 1,3,4-oxadiazole derivatives (3a-3q) were characterized on the basis of LCMS, 1HNMR CNMR, IR and elemental analysis. The title compounds 3a-3q exhibited significant antioxidant efficacy ranging from 34 to 86%and the results of anti-inflammatory evaluation revealed that compounds 3c, 3e and 3d exhibited substantial anti-inflammatory activity of 72, 68 and 65%, respectively, at a dose of 50 mg kg-1.
Conclusion: A significant correlation was observed between the in silico study and the anti-inflammatory results. The anti-inflammatory results highlight the synthesized compounds 3c, 3e and 3d could be considered as possible hit as therapeutic agents.
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