Inhibition of angiogenesis by THAM-derived cotelomers endowed with thalidomide moieties

Bioorg Med Chem Lett. 2004 Jan 19;14(2):421-5. doi: 10.1016/j.bmcl.2003.10.045.

Abstract

The synthesis of a tris(hydroxymethyl)acrylamidomethane (THAM)-derived cotelomer endowed with thalidomide units and a preliminary assessment of its biological activity are described. 4-Carboxy thalidomide and 4-(N-acryloyl) lysine thalidomide derivatives were prepared. The polymerization of these compounds with THAM in the presence of octanethiol as transfer reagent provided a water-soluble telomer bearing several thalidomide units. The ability of this telomer to inhibit angiogenesis in a mouse model of corneal neovascularization was compared to 4-carboxy thalidomide and thalidomide. A significant inhibition in area of neovascularization stimulated by a bFGF pellet was observed only in the mice treated with the telomer.

Publication types

  • Comparative Study

MeSH terms

  • Allantois / blood supply
  • Allantois / drug effects
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cattle
  • Chick Embryo
  • Chorion / blood supply
  • Chorion / drug effects
  • Cornea / blood supply
  • Cornea / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / physiology
  • Thalidomide / chemical synthesis
  • Thalidomide / pharmacology*
  • Tromethamine / chemical synthesis
  • Tromethamine / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Tromethamine
  • Thalidomide