Synthesis, molecular modeling and biological evaluation of 2-(benzylthio)-5-aryloxadiazole derivatives as anti-tumor agents

A series of 2-(benzylthio)-5-aryloxadiazole derivatives have been designed and synthesized, and their biological activities are also evaluated for EGFR inhibitory activity. Fourteen compounds among the twenty compounds are reported for the first time. Their chemical structures are characterized by (1)H NMR, MS, and elemental analysis. Anti-proliferative and EGFR inhibition assay results have demonstrated that compound 3e shows the most potent biological activity (IC(50)?=?1.09?μM for MCF-7 and IC(50)?=?1.51?μM for EGFR). Docking simulation has been performed to position compound 3e into the EGFR active site to determine the probable binding model, with an estimated binding free energy value of?-10.7?kcal/mol. Compound 3e with potent inhibitory activity in tumor growth inhibition may be a promising anti-tumor leading compound for the further research.