喜树碱是从喜树提取物中分离出的能够抗细胞增殖的天然生物碱。由于其溶解性低、稳定性差和显著的不良反应限制了其临床应用，所以在过去的十余年里合成了许多喜树碱衍生物。通过引入极性基团、靶向剂或药效团拼合、前药等在喹啉环、5位和20位进行结构修饰，其中大多数与喜树碱相比显示出更强的效力，对不同的肿瘤细胞具有活性，其中许多对多药耐药肿瘤细胞具有活性。综述了近年来47个新的喜树碱衍生物的合成方法和生物活性，并总结了构效关系，发现在喹啉环和内酯环的羟基上修饰通常可以增强体外抗肿瘤活性，药物递送系统、计算机高通量筛选等新技术的应用为改善喜树碱的溶解性、稳定性，寻找活性较好的先导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

天津市教委科研计划项目（2021KJ125）