Bailly Christian, Bal Christine, Barbier Pascale, Combes Sébastien, Finet Jean-Pierre, Hildebrand Marie-Paule, Peyrot Vincent, Wattez Nicole
INSERM U-524 et Laboratoire de Pharmacologie antitumorale du Centre Oscar Lambret, Institut de Recherches sur le Cancer, Place de Verdun, 59045 Lille, France.
J Med Chem. 2003 Dec 4;46(25):5437-44. doi: 10.1021/jm030903d.
A series of A-ring polymethoxylated neoflavonoids was prepared by ligand coupling reactions involving either Suzuki or Stille reactions. Cytotoxicity studies indicated a potent activity against a CEM leukemia cell line for the compounds presenting a substitution pattern related to that of combretastatin A-4. The two compounds having a 3'-OH and a 4'-OCH(3) substituents on the 4-phenyl B-ring have no effect on human topoisomerases I and II but potently inhibit, in vitro, microtubule assembly. At the cell level, the active compounds were characterized as proapoptotic agents, but they can also trigger cell death via a nonapoptotic pathway.
通过涉及铃木反应或施蒂勒反应的配体偶联反应制备了一系列A环多甲氧基化新黄酮类化合物。细胞毒性研究表明，对于具有与康普他汀A-4相关取代模式的化合物，其对CEM白血病细胞系具有强效活性。在4-苯基B环上具有3'-OH和4'-OCH(3)取代基的两种化合物对人拓扑异构酶I和II没有影响，但在体外能有效抑制微管组装。在细胞水平上，活性化合物被表征为促凋亡剂，但它们也可以通过非凋亡途径引发细胞死亡。
