Two series of 2-substituted benzimidazole conjugated 1,3,4-oxadiazole derivatives were designed, synthesized and evaluated for their cytotoxic activities against the three human cancer cell lines (cervical cancer
(HeLa), breast cancer (MCF-7) and lung cancer (A549)). As the results 14 compounds demonstrated consistent to stronger cytotoxicities compared to the control 5-fluorouracil (5-FU) towards the tested cell lines
including 4c (HeLa); 4b, 4e, 4h, 7i–j, 7m–n, 7s (MCF-7); 7b (MCF-7, A549); 7h (HeLa, MCF-7); and 4d, 4i,
7c (HeLa, MCF-7, A549), with the IC50 ranging from 2.7 to 38µM. Notably, compound 4b illustrated almost
5-fold activity against the MCF-7 while 4d, 4i were 9- and 8-fold (HeLa), 4.5- and 13-fold (MCF-7), 4.7- and
4-fold (A549) increase in activity compared to 5-FU, respectively, and were found as lead compounds. These
findings suggest that compounds 4b, 4d and 4i merit further characterization and can serve as promising
scaffolds in the discovery of new potent anticancer agents.