Synthesis and investigation of biological effects of 2-(substitutedphenyl)-5-(substitutedheteroaryl)-1h benzimidazole derivatives

Cancer, a major cause of human deaths worldwide, is uncontrolled growth of normal cells. Although the extensive advances in discovering anticancer agents, there is still a great demand for development of new anticancer drugs with less side effects and improved selectivity on tumor. The topoisomerase enzymes perform functions related to the maintenance of DNA topology during DNA replication, and transcription and thus they are the targets of a chemotherapeutic agents. Selective targeting of the topoisomerase enzymes for cancer treatment continues to be a highly active area of basic and clinical research. In the light of this information, in this study, some benzimidazole-oxadiazole derivatives were synthesized and tested for their in vitro anticancer activities on five cancer cell lines, including HeLa, MCF7, A549, HepG2 and C6. Their structures were elucidated by IR, 1H-NMR, 13C-NMR, 2D-NMR and HRMS spectroscopic methods. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell lines. Among all screened compounds; 5a, 5b, 5d, 5e, 5k, 5l, 5n and 5o exhibited potent selective cytotoxic activities against various tested cancer cell lines. Furthermore, these potent lead cytotoxic agents were evaluated in terms of their inhibition potency against Topoisomerase I and it was determined that compounds 5a, 5b, 5d, 5e, 5k, 5l, 5n and 5o inhibited the Topoisomerase I. Furthermore, it was found that compounds 5a, 5b, 5d, 5e, 5k, 5l, 5n, and 5o showed cytotoxic activity by inducing apoptosis in cells by Annexin V / PI test. Docking studies for these compounds were performed and probable interactions in the DNA-Topo I enzyme complex was determined. Keywords: Benzimidazole, 1,3,4-Oxadiazole, Anticancer, DNA Topo I.