Rationale Design, Synthesis And In Vitro Anticancer Activity of New 2,5‐Disubstituted‐1,3,4‐Oxadiazole Analogues

Abstract

AbstractTwo new series of oxadiazole analogues (4a–e and 4f–j) were designed based on heterocyclic (1,3,4‐oxadiazole) linked aryl core of IMC‐038525 (tubulin polymerization inhibitor), NSC 784595, and NSC 784597. All the synthesized compounds were synthesized and characterized by IR, NMR, and mass spectral data and the purity of compounds was checked by elemental analysis. Eight compounds were evaluated for their in vitro anticancer activity on 9 different panels of 60 cell lines (60 NCI cancer cell lines) according to the National Cancer Institute (NCI) screening protocol and percent growth (GP) and percent growth inhibition (% GI) was calculated at 10 μM drug concentration. N‐{[5‐(4‐Chlorophenyl)‐1,3,4‐oxadiazol‐2‐yl]methyl}‐4‐methoxyaniline (4 g) showed maximum anticancer activity at 10 μM, and showed maximum sensitivity towards SNB‐75, MDA‐MB‐231/ATCC, T‐47D, 786–0, MCF7, EKVX, PC‐3, HS 578T, MOLT‐4, HCT‐116, HCT‐15, SR, COLO‐205, A549/ATCC, SF‐295, SNB‐19 and RPMI‐8226 with % GIs of 65.48, 60.21, 56.38, 50.36, 49.15, 47.36, 45.16, 41.37, 41.20, 40.02, 38.67, 37.39, 36.61, 34.64, 34.21, 33.77, and 32.92 respectively. Furthermore the compound 4 g showed superior anticancer activity than that of the standard drug Imatinib on 50 human cancer cell lines. The oxadiazoles containing methylene (‐CH2‐) linkage showed comparatively higher anticancer activity.