Anticancer activity of novel benzimidazole derivatives against MCF‐7 cancer cells

Abstract

Cancer takes the third place in the cause of death worldwide after cardiovascular and infectious disease. Benzimidazole derivatives have demonstrated as potential new therapeutics for the treatment of cancer in vitro and in vivo. In this study in order to develop more potent anticancer agents, 27 novel benzimidazole derivatives have been designed and synthesized to evaluate for their in vitro cytotoxic activity in MCF‐7 cells. Cytotoxic effects of synthesized compounds were evaluated using MTT assay and the most active ones were further studied to determine the mechanism of cytotoxic activity. Four active benzimidazole derivatives, compounds A, 13, 22 and 23, were chosen with the IC 50 values of 19.93±1.84, 16.06±7.47, 3.98±0.12, 10.59±1.61 μM in MCF‐7 cells, respectively. Treatment of these compounds at 18 μM for 48 h resulted in rounded and shrunken‐cell shape in MCF‐7 cells. Additionally, change in nuclear morphology after the treatments was determined by DAPI staining of nucleus. We found that selected benzimidazole derivatives significantly increased the nuclear fragmentation comparing to control group in MCF‐7 cells. Morever compounds A, 13, 22 and 23 significantly increased the cleavage of PARP‐1 and led to form an inactive fragment of 89 kDa demonstating that caspases are activated after the treatment of compunds. Taken all together our findings indicate that cytotoxic activities of these benzimidazole‐derived compounds are mediated by apoptotic cell death mechanism. These selected benzimidazole derivatives have the potential in the development of chemotherapeutic agents. Support or Funding Information This work was supported by TUBITAK in 115S016 project.