Synthesis and biological evaluation of novel indolocarbazoles with anti-angiogenic activity

Eur J Med Chem. 2012 Feb:48:108-13. doi: 10.1016/j.ejmech.2011.11.040. Epub 2011 Dec 7.

Abstract

A novel series of indolocarbazoles were synthesized and their antiproliferative activity against HUVEC, LoVo, DLD-1 and ST-486 cell lines, was investigated. Those staurosporine analogs in which a substituted dimethylaminoalkoxy chain was attached to the indolic nitrogen showed interesting activity and selectivity with respect to HUVEC proliferation. The effect on capillary tube formation in 3-dimensional matrigel matrix was studied using the most active compounds. Evaluation of their in vivo anti-angiogenic activity in a murine Lewis lung cancer model was also analyzed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Capillaries / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Collagen / pharmacology
  • Drug Combinations
  • Humans
  • Laminin / pharmacology
  • Lung Neoplasms / blood supply*
  • Lung Neoplasms / drug therapy*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Structure
  • Neovascularization, Pathologic / drug therapy
  • Proteoglycans / pharmacology
  • Spectrophotometry, Infrared
  • Staurosporine / analogs & derivatives*
  • Staurosporine / chemical synthesis
  • Staurosporine / chemistry
  • Staurosporine / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Drug Combinations
  • Laminin
  • Proteoglycans
  • matrigel
  • Collagen
  • Staurosporine