Novel pyrazole-oxadiazole hybrids possessing methanesulphonyl pharmacophore with good gastric safety profile: Design, synthesis, cyclooxygenase inhibition, anti-inflammatory activity and histopathological studies

•Novel pyrazole-oxadiazole derivatives were designed and synthesized.•They were screened for their in vitro COX-1/COX-2 inhibitory activities and in vivo anti-inflammatory activity.•Gastric safety profile and histolopathogical study were assessed.•Molecular docking and ADME prediction were conducted. Novel pyrazole-oxadiazole hydrides were designed as selective COX-2 inhibitors and characterized by spectroscopic and elemental analysis. All synthesized compounds were evaluated for their in vitro COXs inhibition and in vivo anti-inflammatory activities. Compounds 7c, 8b, 10a, 11b and 11d showed moderate to high potency with IC50 range (from 0.04 to 0.06 µM) as COX-2 inhibitors relative to celecoxib (IC50 = 0.05 µM). Also, compounds 4a & b, 7a-d, 8a & b, 10a and 11a & b and 11d showed excellent anti-inflammatory activity with edema inhibition percentage range (from 72 to 98.4%) relative to celecoxib (77.4%). Compounds 4a & b, 7c, 8b, 10a and 11b exhibited a much smaller number of ulcers (UI = 14–27) than celecoxib (UI = 31). The histopathological studies confirmed the gastric safety of these later derivatives. A docking study was performed for all synthesized derivatives inside the COX-2 receptor active site. To predict physicochemical properties, ADME study was performed for the most active compounds. Three of them 7c, 8b and 11d showed bioavailability score (0.55) the same as that of celecoxib. [Display omitted]