具有抗肿瘤活性的茚并异喹啉类化合物研究进展

Advances on indenoisoquinoline compounds with antitumor activities

茚并异喹啉是一类具有抗肿瘤活性的化合物,这类化合物可以克服喜树碱类拓扑异构酶Ⅰ(topoisomerase I,Top1)抑制剂的缺陷,获得活性更加稳定、毒性更小的抗肿瘤化合物。近来发现茚并异喹啉类化合物还具有Top1和酪氨酸-DNA磷酸二酯酶(tyrosyl-DNA phosphodiesterase I,Tdp1)双重抑制作用和潜在的肿瘤预防作用。本文简要介绍了Top1抑制剂的作用机制和茚并异喹啉类的作用优势,重点综述了近年来出现的一些茚并异喹啉酮类化合物的构效关系及研究成果。

Indenoisoquinolines are a class of compounds with antitumor activities. The study of indenoisoquino- lines is to overcome the drawbacks of the camptothecins and to obtain compounds with better activities yet less poison. Recently, indenoisoquinolines were also found to have Topl-Tdpl dual inhibition with a potential role in cancer prevention. This review briefly discusses the mechanism of Topl inhibitors and the advantages of indenoisoquinolines with great emphasis on recent developments of indenoisoquinolines and their structure-activity relationships.