| الوصف: |
Combretastatin A-4 (CA-4), a natural product first isolated from the South African bush willow tree (Combretum caffrum K.), possesses interesting antitumor properties. Due to its capacity to inhibit tubulin polymerization, this stilbenoid shows selective cytostatic activities against various cancer cell lines. Some water-soluble CA-4 derivatives such as CA-4P (fosbretabuline) and AVE8062 (ombrabuline) are currently undergoing clinical trials for the treatment of various cancers. Three series of CA-4 analogues, Z-stilbenes, 1,2-diaryl-1,2-ethanediones and 5,6-diaryl-2,3-dihydropyrazines, were synthesized. In these compounds, the B ring is replaced by various heterocycles (indole, benzofurane, benzothiophene or thiophene) attached at the C2 position. These derivatives were evaluated for their ability to inhibit tubulin assembly. Compound Z- stilbenes bearing a benzo[b]thiophene ring showed an antitubulin activity comparable to that of colchicine and deoxypodophyllotoxine. Its effect on the intracellular organization of microtubules and antimitotic properties were then tested on two keratinocyte cell lines HaCaT and SKV-a. Finally, preliminary essays to the vectorization of this compound in solid lipid nanoparticles (SLN) were carried out ; La combretastatine A-4 (CA-4), produit naturel isolé d’un arbuste d’Afrique du sud (Combretum caffrum K.), a montré des propriétés antitumorales intéressantes. Grâce à sa capacité à empêcher la polymérisation de la tubuline, ce stilbénoïde possède des propriétés cytostatiques sélectives à l’égard de différentes lignées cellulaires cancéreuses. Certains dérivés hydrosolubles de la CA-4 comme la CA-4P (fosbretabuline) et le composé AVE8062 (ombrabuline) sont actuellement en essais cliniques pour le traitement de différents cancers. Trois séries de dérivés de la CA-4 ont été synthétisées : les Z-stilbènes, les 1,2- diaryl-1,2-éthanediones et les 5,6-diaryl-2,3-dihydropyrazines. Dans ces composés, le cycle B est remplacé par divers hétérocycliques (indole, benzofurane, ... |
