Synthesis, biological evaluation, molecular docking, and ADMET studies of some isoxazole-based amides

Abstract

Some isoxazole-based amides were synthesized by the reaction of 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride with various aliphatic, aromatic and heterocyclic amines; characterized by analysis of spectroscopic data and evaluated for in vivo anti-inflammatory, ulcerogenic, and antimicrobial activity. Compounds A1, A7, and A10 were identified as the potent anti-inflammatory agents in carrageenan-induced albino rat paw edema assay exhibiting 92.85–93.57% edema inhibition after 5 h with lower ulcer index (2.5) than the standard diclofinac sodium (6.15). Antibacterial activity against the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was found to be good in comparison with the standard ampicillin in terms of minimum inhibitory concentration values. Anti-inflammatory activity results were supported by molecular docking—possible binding modes, interactions, and docking scores of titled compounds with the active site of cyclooxygenase-2 enzyme. In silico absorption, distribution, metabolism, and excretion–toxicity study was also performed to predict the preliminary pharmacological, pharmacokinetic, and toxicity profile of the synthesized anti-inflammatory agents suggesting that these derivatives have good oral drug like behavior and non-toxic nature.