Inhibition of angiogenesis by THAM-derived cotelomers endowed with thalidomide moieties.
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.
Périno
Sandrine
S
Laboratoire de Chimie Bioorganique et des Systèmes Moléculaires Vectoriels, Faculté des Sciences, 33, rue Louis Pasteur, 84000, Avignon, France.
Contino-Pépin
Christiane
C
Satchi-Fainaro
Ronit
R
Butterfield
Catherine
C
Pucci
Bernard
B
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D013792:Thalidomide / Q000138:chemical synthesis / Q000494:pharmacology*; D014325:Tromethamine / Q000138:chemical synthesis / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D014325:Tromethamine; D013792:Thalidomide