Part I. Synthesis, biological evaluation and docking studies of new 2-furylbenzimidazoles as antiangiogenic agents

Eur J Med Chem. 2014 Nov 24:87:868-80. doi: 10.1016/j.ejmech.2014.01.063. Epub 2014 Feb 1.

Abstract

2-(2-Furyl)-1H-benzimidazoles 3-11 were synthesized and tested for their in vitro VEGF inhibition in MCF-7 cancer cell line. Compound 5a was more potent than Tamoxifen, and compounds 3b, 5a, 5c, 6b, 7a and 10 showed promising potency. Furthermore, compounds (6b, 7a and 10) showed remarkable selective inhibition of COX-2 enzyme close to that of Celecoxcib. Additionally, docking studies were performed using AutoDock 4.2 into the VEGFR2 kinase. Significant correlation exists between the biological activity (IC50 and %VEGF inhibition) against MCF-7 cell line and the molecular docking results (Ki and ΔGb) with correlation coefficients (R(2)) of 0.5513 and 0.4623 respectively. Accordingly, most of the synthesized 2-(2-furyl)-1H-benzimidazoles showed strong antiangiogenic activity against VEGFR2 kinase.

Keywords: 2-(2-Furyl)-1H-benzimidazoles; Angiogenesis; Cytotoxicity; VEGFR2 kinase; Vascular endothelial growth factor (VEGF).

Publication types

  • 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
  • Drug Evaluation, Preclinical
  • Humans
  • MCF-7 Cells
  • Mass Spectrometry
  • Molecular Docking Simulation
  • Proton Magnetic Resonance Spectroscopy
  • Structure-Activity Relationship

Substances

  • Angiogenesis Inhibitors
  • Benzimidazoles