喜树碱抗肿瘤活性官能团E环的结构修饰研究进展

Advances in structural modification of the E ring in camptothecin as an anti-tumor functional group:A review

喜树碱作为蓝果树科喜树Camptotheca acuminata Decne的重要活性成分,是一种广谱高效的抗肿瘤药物。但喜树碱水溶性差、无肿瘤靶向性、毒副作用强和E环结构不稳定等缺陷,使其临床应用受到了极大的限制。喜树碱E环是重要的抗肿瘤活性官能团,其含有一个六元内酯环结构,能够与抑制TopoI特异性结合,抑制TopoI活性。但E环在生理条件下易被水解开环而降低药物活性,且开环后的喜树碱钠盐具有严重的细胞毒性。本文对喜树碱E环的结构修饰研究进行综述,为将来基于喜树碱E环修饰类药物研发提供一定思路。

Camptothecin,an essential active ingredient of Camptotheca acuminata Decne,represents a broad-spectrum and the highly efficient antitumor drug.However,the clinical application of camptothecin is extremely limited due to its poor water solubility,the absence of tumor targeting,highly toxic side effects and the instability of the E ring structure.The E ring in camptothecin is a crucial antitumor active functional group consisting of a six-membered lactone ring structure and capable of specifically binding to and inhibiting Topo I activity.Nevertheless,the E ring is susceptible to hydrolysis under physiological conditions to open the ring and diminish the drug activity,and the ring-opened sodium salt of camptothecin has severe cytotoxicity.This review on the structural modification of the E ring is intended to facilitate the development of future drugs based on the derivation of the E ring of camptothecin.