Synthesis and biological evaluation of epothilone A dimeric compounds

Bioorg Med Chem. 2009 Nov 1;17(21):7435-40. doi: 10.1016/j.bmc.2009.09.032. Epub 2009 Sep 20.

Abstract

The preparation and biological evaluation of a novel series of dimeric epothilone A derivatives (1-6) are described. Two types of diacyl spacers were introduced to establish the various dimeric epothilone A constructs. The effect of these compounds on tubulin polymerization and their cytotoxicity against four different cancer cell lines are reported. Several of the newly synthesized compounds inhibit endothelial cell differentiation and endothelial cell migration that are key steps of the angiogenic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / toxicity
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement
  • Dimerization
  • Drug Screening Assays, Antitumor
  • Endothelial Cells / cytology
  • Epothilones / chemical synthesis*
  • Epothilones / chemistry
  • Epothilones / toxicity
  • Humans
  • Tubulin / metabolism
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / toxicity

Substances

  • Angiogenesis Inhibitors
  • Epothilones
  • Tubulin
  • Tubulin Modulators
  • epothilone A