Synthesis, biological evaluation, and molecular docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents

A series of new 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (6a-6s) as potential telomerase inhibitors have been designed, synthesized, structurally determined, and their biological activities were also evaluated as potential anticancer agents. The bioassay tests demonstrated that compounds 6k, 6l, 6m, 6n and 6s exhibited broad-spectrum antitumor activity with IC50 concentration range from 7.21 μM to 25.87 μM against the four cancer cell lines HEPG2, HELA, SW1116 and BGC823. All the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. The results showed compound 6k possessed the most potent telomerase activity (IC50 = 1.27 ± 0.05 μM). Docking simulation was performed to position compound 6k into the active site of telomerase (3DU6) to determine the probable binding model.