Benzimidazole bearing oxadiazole and triazolo-thiadiazoles nucleus: Design and synthesis as anticancer agents

Two new series of benzimidazole derivatives bearing oxadiazole (4a–l) and triazolo-thiadiazoles (7a–e) ring system were synthesized from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) and screened for their in vitro anticancer activities at the National Cancer Institute (NCI), USA, against full NCI 60 human cell lines on nine cancer subpanel with significant results. Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a–l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a–e)] have been synthesized successfully from4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100μM) with GI50 values ranging from 0.49 to 48.0μM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI50 0.49, TGI 19.9,LC50 >100 and Log10GI50 −6.30, Log10TGI −4.70, Log10LC50 >−4.00).