Kamal A, Atchison K, Daneshtalab M, Micetich R G
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Anticancer Drug Des. 1995 Oct;10(7):545-54.
We have synthesized a number of new podophyllotoxin congeners in which the A-ring is opened and the C-ring is aromatic. These are based on the chemically modified structures of the naturally occurring podophyllum lignan, diphyllin. These have been synthesized by employing the Michael Initiated Ring Closure methodology. These lignans exhibited considerable DNA topoisomerase II inhibition and were devoid of topoisomerase I inhibition; they did not exhibit very significant activities in the in vitro human tumour cell lines assay. The results obtained provide insights into the structure-activity relationships and the design of chemically modified podophyllotoxin congeners useful in cancer chemotherapy.
我们已经合成了许多新的鬼臼毒素类似物，其中A环开环且C环为芳香环。这些类似物基于天然存在的鬼臼木脂素——联苯鬼臼毒素的化学修饰结构。它们是通过迈克尔引发的闭环方法合成的。这些木脂素表现出相当程度的DNA拓扑异构酶II抑制作用，且没有拓扑异构酶I抑制作用；在体外人肿瘤细胞系试验中它们没有表现出非常显著的活性。所获得的结果为结构-活性关系以及对癌症化疗有用的化学修饰鬼臼毒素类似物的设计提供了见解。
