Synthesis and biological evaluation of a polyglutamic acid-dopamine conjugate: a new antiangiogenic agent

J Med Chem. 2011 Jul 28;54(14):5255-9. doi: 10.1021/jm200382r. Epub 2011 Jun 28.

Abstract

Dopamine has previously been shown to inhibit angiogenesis in vitro and in vivo, but its clinical applications in this context are severely limited by its short half-life. Here we report the synthesis of a polyglutamic acid-dopamine conjugate and show that conjugation significantly extends (from 1 to 24 h) dopamine's antiangiogenic activity in vitro and in vivo. These findings form the basis for the development of a new class of agents for the treatment of angiogenesis-dependent diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Capillary Permeability / drug effects
  • Cell Movement
  • Dopamine / chemical synthesis*
  • Dopamine / chemistry
  • Dopamine / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology
  • Female
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Microvessels / drug effects
  • Microvessels / physiology
  • Neovascularization, Physiologic / drug effects
  • Polyglutamic Acid / chemistry*
  • Structure-Activity Relationship
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Polyglutamic Acid
  • Dopamine