Synthesis, Characterization, DFT, Docking Studies and Molecular Dynamics of Some 3-Phenyl-5-Furan Isoxazole Derivatives as Anti-inflammatory and Anti-ulcer Agents

Abstract A vast number of nitrogen heterocyclic derivatives comprising oxygen atom is considered as a valuable combination of therapeutic agents in curative chemistry. In particular, isoxazole, a five-member heterocyclic ring, is detected along with some of the marketed drugs such as danazol, flucloxacillin, dicloxacillin, cloxacillin, and valdecoxib which are known as an anti-inflammatory drug. The incorporation of the isoxazole ring can offer enhanced physical-chemical properties to show a wide scope of targets and diverse biological applications. In this view, the title compounds 5(a-h) were synthesized in good yield starting from different substituted benzaldehydes 1(a-h) and 2-acetyl furan (2) to afford chalcone derivatives 3(a-h). Further, compounds 3(a-h) refluxed with hydroxylamine hydrochloride to afford the title compounds 5(a-h). The purified compounds were explained by spectroscopic procedures (FT-IR, 1H NMR, 13CNMR, and LC-MS), and lastly, the title compounds 5(a-h) were screened for COX-1, COX-2, LOX furthermore, anti-ulcer action. In-vitro, study reveals that compound (5f) is potent with the IC50 values 9.16±0.38 μM (COX-2), 8.15±0.16 μM (15-LOX), and 42.41±0.29 μg mL−1 (anti-ulcer activity against H+/K+ ATPase) which are very close to the standard omeprazole. Besides, in-silico putative binding, possess of compound (5f) was studied by performing molecular docking and molecular dynamic along with ADME/Tox to evaluate its bioavailability and toxicity studies.