IN SILICO MOLECULAR DOCKING STUDIES OF NOVEL 1,3,4-OXADIAZOLE DERIVATIVES AS POTENT MULTI-TARGET AGENTS: EXPLORING ANTIMICROBIAL, ANTICANCER, ANTIFUNGAL, AND ANTI-INFLAMMATORY POTENTIAL

Asif Khan, Dr. Omprakash Goshain*, Dr. Ashwin Saxena, Gurjeet Singh

ABSTRACT

The rising prevalence of multidrug-resistant pathogens and complex diseases such as cancer necessitates the development of multi-target therapeutic agents. In this study, two novel 1,3,4-oxadiazole derivatives—Compound 1 [2-(4-fluorophenyl)-5-(pyridin-3-yl)-1,3,4-oxadiazole] and Compound 2 [2-(4-chlorophenyl)-5-(thiophen-2-ylmethyl)-1,3,4-oxadiazole]—were evaluated as potential multi-target inhibitors through molecular docking simulations using AutoDock Vina. The compounds were docked against five key therapeutic targets: DNA gyrase (2XCS), EGFR (4HJO), VEGFR-2 (1Y6A), lanosterol 14α-demethylase/CYP51 (5TZ1), and cyclooxygenase/COX (5KIR). Compound 1 demonstrated superior binding affinities with top Vina scores of −9.1 kcal/mol (COX), −8.8 kcal/mol (EGFR), −8.5 kcal/mol (DNA gyrase and CYP51), and −8.3 kcal/mol (VEGFR-2). Compound 2 exhibited consistently strong but slightly lower affinities (ranging from −8.3 to −8.0 kcal/mol). Detailed analysis of binding poses, cavity sizes, and grid parameters revealed favorable hydrogen bonding, hydrophobic, and π-π stacking interactions. These results highlight the 1,3,4-oxadiazole scaffold’s versatility as a privileged structure for multi-target directed ligands. Compound 1 emerges as a promising lead for further synthesis, in vitro validation, and optimization as a broad-spectrum therapeutic agent against cancer, bacterial/fungal infections, and inflammation. (148 words).

Keywords: 1,3,4-Oxadiazole, Molecular docking, Multi-target ligands, Anticancer agents, Antimicrobial activity.