新的4′-去甲表鬼臼衍生物的合成及其抗癌活性

Synthesis and Anti-cancer Activity of Novel Derivatives of 4′-Demethylepipodophyllotoxin

根据鬼臼毒衍生物和 5 氟尿嘧啶的抗癌机理和构效关系 ,合成了 7个新的 4β 5 氟尿嘧啶取代 4′ 去甲表鬼臼毒衍生物 .在抑制金属基质蛋白酶I和胶原酶I活性测试中 ,化合物 2 .4和 2 .6的抑制活性比鬼臼乙叉甙 (VP 16 )和5 氟尿嘧啶 (5 Fu)强 3倍和 5倍 ,在治疗癌细胞转移方面值得进一步探讨 .

According to the structure-activity relationship of podophyllotoxin derivatives, along with the different anti-cancer mechanism between demethylepipodophyllotoxin and 5-fluorouracil seven novel 4beta-5-fluorouracil substituted 4'-demethylepipodophyllotoxin derivatives were synthesized and evaluated as inhibitors of stromelysin-1 as well as collagenase-1. Among them, compounds 2. 4 and 2. 6 exhibited superior inhibitor activity against stromelysin-1 than that of prototype drugs, etoposide and 5-fluorouracil (inhibitory ratio were 80.2, 80.0, 25.5 and 15.8 for compounds 2.4, 2.6, etoposide and 5-Fu, respectively).