【摘要】 喜树碱及其衍生物有较强的抗癌活性,作用靶点为拓扑异构酶Ⅰ,构效关系显示喜树碱内酯的E环对其活性影响较大,并确定20位为S型是发挥抗癌作用的重点部位;调整A环和B环尤其是改变9、10、11位基团,可得到水溶性增大、抗癌活性强的衍生物。喜树碱已成为临床评价较高的抗癌药物。至2002年已设计合成15个新化合物,其中3个已上市,12个正处于临床阶段。作者对2002年以前有关喜树碱及其衍生物的合成及构效关系的研究情况进行综述。更多还原

【Abstract】 The natural product camptothecin and its derivatives are a highly promising class of antitumors. The molecular target has been shown to be topoisomerase I . The structure-activity relationship indicated the importance of the lactone E-ring of camptothecin for activity, 20(S)-configuraion for activity was recognized. Modifications in A-ring and B-ring, particularly in the 9,10 and 11 positions, highly potent, water-soluble analogues have been identified. Camptothecins have become a class of anticancer compounds of very high clinical value. Today, with three successful compounds in clinical practice and 12 compounds in clinical development. In this article, the development of the structure-activity relationship and synthetic camptothecin analogues is reviewed.更多还原