Abstract

A series of 3-(furan-2-yl)-5-(substituted phenyl)-4,5-dihydro-1,2-oxazole derivatives (2a to j) were synthesized by Claisen Schmidt condensation of 2-acetyl furan with different types of aromatic aldehyde, as chalcones and their subsequent cyclization to  4,5-dihydro-1,2-oxazole with hydroxylamine hydrochloride. The chemical structures of the synthesized compounds were confirmed by IR, ¹H NMR, ¹³C-NMR and mass spectrometric data. This study further involves evaluation of synthesized compounds for antidepressant and antianxiety activities using force swimming test (FST) and elevated plus maze method, respectively. Most of the tested compounds were found to be moderate to significant activities at the dose level of 10 mg/kg, compared to reference drugs imipramine and diazepam, respectively. Compound 4-[3-(furan-2-yl)-4,5-dihydro-1,2-oxazol-5-yl]phenol (2e)  emerged as the most potent antidepressant agent acting through monoamine oxidase (MAO) inhibition without any significant neurotoxicity. The molecular docking study were also carried out on the falcipain-2 receptor (PDB id: 2Z5X) for all the compounds and compound 2e was found to occupy in the receptor cavity and forms hydrogen bond and hydrophobic interactions with active residues.

Key words: Isoxazoline, Claisen Schmidt condensation, antidepressant, antianxiety.