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

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).

• Authors: Rangaswamy Roopashree, Chakrabhavi Dhananjaya Mohan, Toreshettahally Ramesh Swaroop, Swamy Jagadish, Byregowda Raghava, Kyathegowdanadoddi Srinivas Balaji, Shankar Jayarama, Basappa, Kanchugarakoppal Subbegowda Rangappa
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 12 Pg. 2589-93 (Jun 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 25920563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• Angiogenesis Inhibitors (chemical synthesis, pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology, therapeutic use)
• Ascites
• Bisbenzimidazole (chemistry, pharmacology, 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