中文摘要：

喜树碱是1966年由喜树中分离而来的一种五环结构的生物碱,早期对其抗肿瘤活性的发现更是引发了科学家们对此类化合物极大的研究兴趣,现在已经证实喜树碱类化合物主要是通过抑制在DNA代谢过程中发挥重要作用的I型拓扑异构酶。但其自身因水溶性差、毒副作用强,在临床应用上易出现不良反应。半个世纪以来,国内外研究者在对其作用机制及构效关系的研究基础上,开发出了数以百计的喜树碱类衍生物,很多已经进入临床或临床前研究。但目前仅有两种喜树碱类的化合物拓扑替康和依立替康被美国FDA批准应用于临床上肿瘤的治疗。本文就已上市的喜树碱类化合物以及喜树碱类抗肿瘤药物开发的挑战进行了综述。

英文摘要：

Camptothecin（CPT）, a pentacyclic alkaloid isolated by Wall in 1966 from the Chinese tree Camptotheca acuminate.The study which possesses an interesting antitumor activity has aroused great attention of scientists. It has been found out that the cytotoxic activity of CPT was attributed to the mechanism of action involving the nuclear enzyme classified as type I DNA topoisomerase. However, the poor solubility in water and significant side effects of CPT has strongly restricted its clinical uses. During the half century, based on the studies of mechanism of action, many derivatives of CPT have been synthesized and some of which are in various stages of preclinical and clinical development. Among them, only two derivatives, topotecan and irinotecan, have successfully entered into the market and are used as topoisomerase I poisons in clinical practice. This review summarizes the progress and challenges of developing CPT derived anticancer drugs.