Synthesis, β-Glucuronidase Inhibitory Activity, and Molecular Docking Study of Oxazole Derivatives

A series of 4-aryl-2-[2-(arylmethylidene)hydrazinyl]-1,3-oxazoles were synthesized from the corre­sponding aromatic aldehyde semicarbazones and phenacyl bromides. The synthesized compounds were characterized by NMR and high-resolution mass spectra and evaluated for their inhibitory activity against β-glucuronidase. All compounds showed a varying degree of inhibitory potential (IC 50 ) ranging from 2.40±0.10 to 43.20±0.20 µM in comparison with the standard drug D-saccharic acid 1,4-lactone (IC 50 = 48.4±1.25 µM). The most potent analogs displayed IC 50 values of 2.40±0.10 and 5.30±0.20 µM. A limited structure–activity relationship analysis was performed, which showed that the nature, position, and number of the substituents on phenyl ring are the major factors responsible for the inhibitory activity. A molecular docking study was carried out to determine the binding interaction of the most potent compounds in the active site of the enzyme.