New 1,3,4-oxadiazole-chalcone/benzimidazole hybrids as potent antiproliferative agents

A series of new 1,3,4-oxadiazole-chalcone/benzimidazole hybrids 9a-o and 10a-k were designed and synthesized as potential antiproliferative agents. Hybrids 9a-o exhibited remarkable antiproliferative activities on different NCI-60 cell lines in a single-dose assay. The antiproliferative activities of the newly synthesized compounds were evaluated against a panel of four human cancer cell lines (A-549, MCF-7, Panc-1, and HT-29). Compounds 9g-i and their oxygen isosteres, 10f-h, exhibited promising antiproliferative activities with IC₅₀ values ranging from 0.80 to 2.27 µM compared to doxorubicin (IC₅₀ ranging from 0.90 to 1.41 µM). Furthermore, the inhibitory potency of these compounds against the epidermal growth factor receptor (EGFR) and BRAF^V600E kinases was evaluated using erlotinib as a reference drug. Molecular modeling studies were done to investigate the binding mode of the most active hybrids in the ATP binding site of EGFR.