Formulation Of Novel 1,3,4-Oxadiazole Entities And Examination Of Their Antioxidant Efficiency

Abstract

The 1,3,4-oxadiazole nucleus is a privileged five-membered heterocyclic scaffold with sustained relevance in
medicinal chemistry because of its bioisosteric character and capacity to stabilise radical intermediates. The present
work was framed to formulate a novel series of 2,5-disubstituted 1,3,4-oxadiazole entities (OX-1 to OX-8) bearing
electron-donating and electron-withdrawing substituents, and to assess their antioxidant competence. Aromatic acid
hydrazides were synthesised through Fischer esterification, hydrazinolysis, and subsequent cyclodehydration with
phosphorus oxychloride (POCl₃) at reflux. Structures were verified through FT-IR, ¹H NMR, ¹³C NMR, and LC-MS.
Antioxidant potential was examined through DPPH, ABTS, hydrogen peroxide (H₂O₂), nitric oxide (NO), and ferric
reducing antioxidant power (FRAP) assays, with ascorbic acid as reference. Results indicated that OX-6, carrying a
4-hydroxy-3-methoxyphenyl group, exhibited the strongest efficiency (DPPH IC₅₀ = 14.82 μg/mL; ABTS IC₅₀ = 11.46
μg/mL; FRAP = 1187 μM Fe²⁺/g). Hypothesis-testing by one-way ANOVA confirmed substituent-dependent
differences (p < 0.05). Electron-donating hydroxyl and methoxy groups markedly enhanced radical scavenging, while
nitro and halogen groups reduced activity. The study concludes that properly substituted 1,3,4-oxadiazoles are
valuable candidates for antioxidant drug development.