喜树碱类药物的研究与开发

Research Progress and Development of Camptothecin Derivatives

喜树碱是从中药喜树中分离得到的单体成分,作为世界上第三大植物抗癌药,喜树碱及其多种衍生物是临床常用的广谱抗癌药物。自20世纪70年代发现喜树碱后,科学家们对喜树碱类化合物的构效关系、结构修饰、药效药理等方面开展了大量研究工作,并开发出拓扑替康、依立替康、贝洛替康等喜树碱类抗癌药。直到40多年后的今天,科学家们对于喜树碱类药物的研究依然活跃,对其生物合成、新剂型开发等方面的关注也成为研究的新方向。作为源于中药单体成分而开发成药的成功典范,喜树碱类化合物的研发历程对我们当前开发中药单体活性成分新药无疑是有益的借鉴。本文对喜树碱类药物的研发及其新进展进行综述,与同行一起回顾喜树碱的开发历程和相关研究,以期对源于中药的新药开发带来一些思考。

As the third anticancer-drug from plants in the world, camptothecin is an effective monomer composition isolated from the traditional herb, Camptotheca Acuminata, which is planted only in China with its derivatives commonly used in clinical as broad spectrum anticancer drugs. Since its discovery in 1970 s, many researches had emerged, mainly focusing on the modification, structure activity relationship and pharmacological activity of camptothecin. These great successes pressed ahead the development of a series of camptothecin-like drugs, such as Topotecan, Irinotecan and Belotecan. Nowdays, studies of camptothecins are still the hotspots, which also broaden to the cultivation of tissue and the development of new forms. As the representative of drugs origined from effective monomer compositions of Chinese materia medica（CMM）, the process of camptothecin research is worth the learning of CMM’s drug discovery. This review summerized the history, ongoing development of camptothecins and the drug development of CMM, in hope of retrospecting with readers and bringing some new thoughts to them.