Synthesis of 1,2,4-oxadiazole derivatives: anticancer and 3D QSAR studies

A 3D QSAR study was performed on 1,2,4-oxadiazole derivatives using the [(SW) kNN MFA], CoMFA, and CoMSIA techniques. On the basis of 3D QSAR outcomes, new molecules were designed by substituting different substituents. These designed compounds were synthesized and confirmed their synthesis by spectroscopic techniques. The synthesized compounds were screened for their anticancer activity against different cancer cell lines. Compound 2-[3-(pyridine-4-yl)-1,2,4-oxadiazol-5-yl]benzo[ d ]thiazole showed equipotent (IC 50 = 4.96 μM) as 5-fluorouracil (IC 50 = 3.2 μM) against colon (CaCo-2) cancer cell line, and compound [2-[3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzo[ d ]thiazol-4-yl]methanol showed equipotent activity (IC 50 = 0.35 μM) as compared to 5-fluorouracil (IC 50 = 0.23 μM) against colorectal (DLD1) cancer cell line. Compound 2-[3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-5-yl]benzo[ d ]thiazole was found to be 4–5 less potent (IC 50 = 19.40 μM) as paclitaxel (IC 50 = 4.10 μM) against breast (T47D) cancer cell line, and compound 4-[5-(benzo[ d ]thiazol-2-yl)-1,2,4-oxadiazol-3-yl]benzene-1,2-diol was found about 10 times less potent (IC 50 = 15.7 μM) than mitomycin (IC 50 = 1.50 μM) against prostate (PC-3) cancer cell line. These results disclose the discovery of new 1,2,4-oxadiazole-based anticancer drugs. Graphic abstract