Synthesis, anti-inflammatory properties, molecular modelling and potential COX-2, TNF-α, PGE2 and IL1β inhibitors of pyrazole-based scaffolds

•A variety of tri-substituted pyrazole derivatives 3-15 were synthesized and evaluated for their anti-inflammatory, analgesic, antipyretic and ulcerogenic properties.•Some of the tested conjugates showed promising biological observations comparable to standard reference celecoxib, in addition, to their safety margin for gastric mucosa when evaluated for their ulcer-producing activity.•The most potent derivatives 3a, 3b, 6, 8 and 11 were assayed for their COX-2, TNF-α, PGE2 and IL1β levels in rat paws using the carrageenan inflammation model with the ELISA kit.•Compound 8 possesses the best promising anti-inflammatory observations, antipyretic effect and long-lasting analgesic activity without ulcerogenic potential in addition to showing mutual inhibitory effects on all tested enzymes.•A molecular docking study was introduced to recognize the binding interactions of the most potent candidates into active sites of COX-2 and TNF-α.•Compound 8 has the best binding interaction scores with both targeted enzymes that supported its obtained bio-observations and proves that it has the potential to be developed into an anti-inflammatory drug.