Design, synthesis, and in-vitro antiproliferative effect of some novel 1,3,4-oxadiazole derivatives bearing benzimidazole nucleus

Abstract

Background and objectives Development of a novel compound containing a heterocyclic nucleus as an anticancer therapeutic agent is the most important focal point in medicinal chemistry. Programmed cell death or apoptosis is a fundamental phenomenon and plays a central role in immune regulation, embryogenesis, and general tissue homeostasis. Therefore, identification of novel potent, selective, and less toxic anticancer agents is one of the most crucial concerns. Materials and methods A series of 4-{1-[(4-acetyl-5-(substituted)-4,5-dihydro-1,3,4-oxadiazol-2-yl)methyl]-5-nitro-1 H- benzimidazol-2-yl}benzonitrile 6 (I-IV) and novel 4-{5-substituted-1-[(4,5-disubstituted)-4,5-dihydro-1,3,4-oxadiazol-2-yl)methyl]-5-nitro-1 H- benzimidazol-2-yl}benzonitrile 7 (V-XXXIII) derivatives were synthesized. Results and conclusion Nine of them were selected by the Department of Biotechnology Drug Discovery R&D, Century Pharmaceuticals Ltd, for evaluation of their in-vitro anticancer activity. Three of the investigated compounds, 7.X, 7.XIX , and 7.XXIV , displayed in-vitro anticancer activity in the primary assay. These compounds were selected for a full anticancer screening against a three-cell panel MTT assay, and they showed a nonselective broad spectrum antiproliferative activity against L929, HCT15, and Hep2 cancer cell lines. Compound 7.XIX showed antiproliferative activity, which can be comparable to that of 5-fluorouracil, methotrexate, and daunorubicin, and this compound has been identified as a promising lead compound.