喜樹堿是從喜樹提取物中分離出的能夠抗細(xì)胞增殖的天然生物堿。由于其溶解性低、穩(wěn)定性差和顯著的不良反應(yīng)限制了其臨床應(yīng)用，所以在過去的十余年里合成了許多喜樹堿衍生物。通過引入極性基團(tuán)、靶向劑或藥效團(tuán)拼合、前藥等在喹啉環(huán)、5位和20位進(jìn)行結(jié)構(gòu)修飾，其中大多數(shù)與喜樹堿相比顯示出更強(qiáng)的效力，對不同的腫瘤細(xì)胞具有活性，其中許多對多藥耐藥腫瘤細(xì)胞具有活性。綜述了近年來47個新的喜樹堿衍生物的合成方法和生物活性，并總結(jié)了構(gòu)效關(guān)系，發(fā)現(xiàn)在喹啉環(huán)和內(nèi)酯環(huán)的羥基上修飾通?？梢栽鰪?qiáng)體外抗腫瘤活性，藥物遞送系統(tǒng)、計(jì)算機(jī)高通量篩選等新技術(shù)的應(yīng)用為改善喜樹堿的溶解性、穩(wěn)定性，尋找活性較好的先導(dǎo)化合物拓展了新思路。

Camptothecin (CPT) is an effective cytotoxic natural alkaloid isolated from camptotheca acantha extract with broadspectrum antiproliferative activity. Its low solubility, instability, and significant toxicity limit its clinical application, therefore, intensive medicinal chemistry efforts have generated numerous CPT derivatives over the last decade. Most of the CPT analogues which introduced polar groups, targeting agents, pharmacophore splice and prodrugs at quinoline rings, C-5 and C-20 displayed greater potency compared to the parent CPT and are active against different cancers and many of them were active against multidrug resistant tumors. This review will focus on structural modification, bioactivity and structure-activity relationship of of 47 new camptothecin derivatives in recent years. It was found that modification of quinoline ring and hydroxyls of lactone ring can generally enhance the antitumor activity in vitro. The application of new technologies such as drug delivery system and computer high-throughput screening expand new ideas to improve the solubility and stability of camptothecin and search for lead compounds with good bioactivity.

R284.3；R979.1

天津市教委科研計(jì)劃項(xiàng)目（2021KJ125）