Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues.
Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues.
复制标题
CC-1065类似物的葡萄糖醛酸衍生物的合成和初步细胞毒性研究。
DOI：
10.1016/s0968-0896(02)00603-x
复制
发表时间：
2003
影响因子：
3.5
通讯作者：
Larrick,JamesW
中科院分区：
文献类型：
--
作者：
Wang,Yuqiang;Yuan,Huiling;Wright,SusanC;Wang,Hong;Larrick,JamesW
带有 CBI 的 CC-1065 类似物的葡萄糖苷酸衍生物已被合成，并测试了它们对 U937 白血病细胞的细胞毒性。新化合物在体外显示出有效的抗肿瘤活性。化合物1和2及其相应的葡萄糖醛酸苷3和4的IC50值分别为0.6、0.1、1.4和0.6nM。葡萄糖醛酸苷 3 的毒性比其羟基对应物 1 低约 2 倍，葡萄糖醛酸苷 4 的毒性比其羟基对应物 2 低约 6 倍。葡萄糖醛酸苷 3 和 4 在 ADEPT 方法中的用途可能有限。然而，它们可以常规方式用作抗肿瘤剂。
Glucuronide derivatives of CBI-bearing CC-1065 analogues have been synthesized, and their cytotoxicities tested against U937 leukemia cells. The new compounds show potent antitumor activity in vitro. Compounds 1 and 2, and their corresponding glucuronides 3 and 4 have IC50values of 0.6, 0.1, 1.4 and 0.6nM, respectively. Glucuronide 3 is approximately 2-fold less toxic than its hydroxyl counterpart 1, and glucuronide 4 is approximately 6-fold less toxic than its hydroxyl counterpart 2. Glucuronides 3 and 4 may have limited use in the ADEPT approach. However, they may be used as antitumor agents in a conventional way.