Thomas Craig J, Rahier Nicolas J, Hecht Sidney M
Departments of Chemistry and Biology, University of Virginia, Charlottesville, VA 22901, USA.
Bioorg Med Chem. 2004 Apr 1;12(7):1585-604. doi: 10.1016/j.bmc.2003.11.036.
This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.
本综述详细讨论了喜树碱（一种强效抗肿瘤抗生素）药物化学的最新进展。目前有两种喜树碱类似物已被批准用于临床作为抗肿瘤药物，还有其他几种正在进行临床试验。喜树碱具有一种新颖的作用机制，涉及通过DNA拓扑异构酶I抑制DNA松弛，更具体地说是稳定拓扑异构酶I与DNA之间形成的共价二元复合物。本综述总结了喜树碱作用机制的研究现状，包括拓扑异构酶I抑制和其他细胞反应。还讨论了喜树碱的现代合成方法以及几种半合成方法。最后，对喜树碱的新型重要类似物及其对当前构效关系的贡献进行了系统评估。
