Novel synthetic bisbenzimidazole that targets angiogenesis in Ehrlich ascites carcinoma bearing mice

Bioorg Med Chem Lett. 2015 Jun 15;25(12):2589-93. doi: 10.1016/j.bmcl.2015.04.010. Epub 2015 Apr 11.

Abstract

Cancer is a leading cause of death in developed countries and second cause in developing countries. Herein we are reporting the synthesis of novel bisbenzimidazole derivatives and their anticancer properties. Among the newly synthesized bisbenzimidazoles, 3-(4-flurophenylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole (FDPB) presented as a potent antiproliferative agent against HeLa, HCT116 and A549 cells with selectivity over normal Vero cells (IC50 >50 μM). Additionally, we evaluated the efficacy of lead compound against Ehrlich ascites tumor (EAT) bearing mice for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature and production of Vascular Endothelial Growth Factor (VEGF).

Keywords: Angiogenesis; Antiproliferative; Bisbenzimidazole; Ehrlich ascites tumor; Micro vessel density; Vascular Endothelial Growth Factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Ascites
  • Bisbenzimidazole / chemistry*
  • Bisbenzimidazole / pharmacology
  • Bisbenzimidazole / therapeutic use
  • Body Weight / drug effects
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Down-Regulation / drug effects
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Vascular Endothelial Growth Factor A / metabolism
  • Vero Cells

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • Bisbenzimidazole