Synthesis, biological evaluation, and docking studies of new 2-furylbenzimidazoles as anti-angiogenic agents: part II

Arch Pharm (Weinheim). 2014 Apr;347(4):291-304. doi: 10.1002/ardp.201300356. Epub 2014 Feb 5.

Abstract

The 2-(5-methyl-2-furyl)-1H-benzimidazole moiety has shown promising activity against vascular endothelial growth factor (VEGF)-induced angiogenesis. In part I of this study, we have synthesized new analogs and tested their anti-angiogenic potentials. Here, we continue our previous study with different new analogs. Some compounds show promising cytotoxic activity against the human breast cancer cell line MCF-7, with IC50 in the range of 7.80-13.90 µg/mL, and exhibited remarkable in vitro inhibition against VEGF in the MCF-7 cancer cell line, with 95-98% of inhibition in comparison to tamoxifen as reference (IC50: 8.00 µg/mL, % of inhibition = 98%). Additionally, a molecular docking study was carried out to gain insight into plausible binding modes and to understand the structure-activity relationships of the synthesized compounds.

Keywords: 2-(2-Furyl)-1H-benzimidazoles; Angiogenesis; Cytotoxicity; Molecular modeling; Vascular endothelial growth factor (VEGF).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Structure-Activity Relationship
  • Tamoxifen / pharmacology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Benzimidazoles
  • Vascular Endothelial Growth Factor A
  • Tamoxifen