Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins
Synthesis and biological evaluation of 4-arylcoumarin analogues of combretastatins
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DOI：
10.1021/jm030903d
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发表时间：
2003-12-04
影响因子：
7.3
通讯作者：
Wattez, N
中科院分区：
文献类型：
--
作者：
Bailly, C;Bal, C;Wattez, N
通过包括Suzuki反应和Stille反应的配体偶联反应，合成了一系列A环多甲氧基化新黄酮类化合物。细胞毒性研究表明，这些化合物具有很强的抗CEM白血病细胞株的活性，其取代模式与comretataatin A-4的取代模式有关。在4-苯基B环上有3‘-OH和4’-OCH3取代基的两个化合物对人类拓扑异构酶I和II没有影响，但在体外有效地抑制了微管的组装。在细胞水平上，活性化合物被认为是促凋亡剂，但它们也可以通过非凋亡性途径触发细胞死亡。
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'-OCH3 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.