Synthesis and Anti-inflammatory Activities of 4-Arylidene-2-phenyloxazol-5(4H)-one Derivatives

Abstract

In this study, four different 4-arylidene-2-phenyloxazol-5(4H)-ones (5a-d), were synthesized via the Erlenmeyer-Plöchl reaction and characterized by FT-IR, 1H NMR, 13C NMR and mass spectroscopic techniques. Evaluation of their in vitro anti-inflammatory activities using the heat-induced human red blood cell (HRBC) membrane stabilization assay revealed concentration dependent inhibitory effects. The IC50 values of 5a, 5b, 5c and 5d were reported as 4.65 ± 0.22 mM, 7.34 ± 0.28 mM, 5.23 ± 0.18 mM and 1.96 ± 0.09 mM, respectively. O-Acetyl salicylic acid as standard showed its IC50 value at 6.41 ± 0.18 mM. Docking studies against human cyclooxygenase (COX) 1 and 2 revealed affinities of the compounds to binding cavities of COX enzymes. Particularly, compound 5d exhibited remarkable activity in both HRBC membrane stabilization and the formation of hydrogen bonds with binding cavities. This suggests a potential correlation between the number of hydroxyl groups of oxazolone derivatives and the enhancement of anti-inflammatory activity.