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目的 研究在喜树碱类化合物A环9,10位上增加一个六元环后,所得衍生物的生物活性的变化情况。 方法分别以10 羟基喜树碱和7 乙基 10 羟基喜树碱(SN 38)为原料,通过三或四步反应得到一系列相应的A环上修饰的喜树碱衍生物,用MTT法评价了它们的细胞毒活性,用小鼠肝癌H22评价它们体内的肿瘤抑制率。结果 5 个六环喜树碱衍生物为目标化合物,10个衍生物为新化合物。结论喜树碱A环的9,10位增加一个“1,4 氧嗪 2 酮”六元环后,其抗肿瘤活性要比喜树碱或10 羟基喜树碱的活性降低。
Objective To study the changes of the biological activity of the obtained derivatives after adding a six-membered ring to the 9th and 10th positions of the A ring of camptothecin compounds. Methods A series of corresponding A-ring modified camptothecin derivatives were obtained by three or four reaction steps using 10-hydroxycamptothecin and 7-ethyl-10-hydroxycamptothecin (SN 38) Their cytotoxic activity was evaluated using mouse hepatocellular carcinoma H22 to evaluate their tumor inhibition rate in vivo. Results Five hexacyclic camptothecin derivatives were the target compounds and ten derivatives were new compounds. CONCLUSIONS: The anticancer activity of camptothecin ring A at position 9 and 10 after addition of a “1,4-oxazinone” six-membered ring is lower than that of camptothecin or 10-hydroxycamptothecin.