Objective: Pharmacological evaluate of hydrazide, marginal analogues of naproxen, flurbiprofen and ibuprofen, well established COX inhibitors, with the goal to identifying a Cyclooxygenase (COX) inhibitor(s) with optimum potency and efficacy. The synthesized and characterized analogues were tested for their acute toxicity, anti-inflammatory, analgesic and antipyretic activities as per reported bioassay models. Molecular docking analysis was also performed to predict ligand: protein interactions. Method: Acute toxicity, anti-inflammatory, analgesic and antipyretic activities were performed in accordance with well-established reported bioassay models for the purposes. Results: No acute toxicity was observed at intraperitoneal doses of 50, 100 and 150mg/Kg body weight. Biological assays revealed that test compounds-I to-IV have highly significant antiinflammatory and peripheral analgesic activities. Antipyretic test revealed that test compounds I, II, III have highly significant antipyretic activity while IV in the doses of 20mg and 30 mg has significant and in the dose of 50 mg/Kb body weight has highly significant antipyretic activity. The molecular modelling revealed strong inhibitory interactions of the four compounds. The most suitable poses have higher docking score (energies) compared to flurbiprofen (reference ligand), that confirms highly significant anti-inflammatory and analgesic activities of the dimers. Conclusion: The synthesized hydrazide analogues have highly significant pharmacological activities and have the potential to be further explored as new drug molecules.
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