PubMed:31144429 JSONTXT 6 Projects

Design and Synthesis of 2-(5-Phenylindol-3-yl)benzimidazole Derivatives with Antiproliferative Effects towards Triple-Negative Breast Cancer Cells by Activation of ROS-Mediated Mitochondria Dysfunction. Benzimidazole derivatives are widely studied because of their broad-spectrum biological activity, such as antitumor properties and excellent fluorescence performance. Herein, two types of 2-(5-phenylindol-3-yl)benzimidazole derivatives (1 a-1 h and 2 a-2 e) were rationally designed and synthesized. When these compounds were investigated in vitro anti-screening assays, we found that all of them possessed antitumor effect, in particular compound 1 b, which showed an outstanding antiproliferative effect on MDA-MB-231 cells (IC50 ≈2.6 μm). A study of the drug action mechanisms in cells showed that the antitumor activity of the compounds is proportional to their lipophilicity and cellular uptake; the tested compounds all entered the lysosome of MDA-MB-231 cells and caused changes in the levels of reactive oxygen species (ROS), and then caused mitochondrial damage. Apparent differences in the ROS levels for each compound suggest that the lethality of these compounds towards MDA-MB-231 cells is closely related to the ROS levels. Taken together, this study not only provides a theoretical basis for 2-(5-phenylindol-3-yl)benzimidazole anticarcinogens but also offers new thinking on the rational design of next-generation antitumor benzimidazole derivatives.