Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents.
Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents.
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作为有效细胞毒剂的新型 7-(N-取代-甲基)-喜树碱衍生物的设计和合成
DOI：
10.1016/j.bmcl.2014.06.060
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发表时间：
2014-08-15
影响因子：
2.7
通讯作者：
Lee KH
中科院分区：
文献类型：
--
作者：
Zhao XB;Goto M;Song ZL;Morris-Natschke SL;Zhao Y;Wu D;Yang L;Li SG;Liu YQ;Zhu GX;Wu XB;Lee KH
设计、合成了一系列新的7-（N-取代甲基）-喜树碱衍生物，并对4种人肿瘤细胞株A-549、MDA-MB-231、KB和KBvin进行了体外细胞毒性评价。所有衍生物均显示出对测试的肿瘤细胞系的有希望的体外细胞毒活性，IC 50值范围为0.0023至1.11 μM，并且与拓扑替康一样或更强。化合物9d、9 e和9 r在所有制备的衍生物中表现出最高的抗增殖活性。此外，所有的化合物都比紫杉醇更有效地对抗多药耐药（MDR）KBvin亚系。化合物9d、9 e和9 r具有简洁有效的合成和有效的细胞毒性特征，特别是对KBvin的显著活性，值得进一步开发作为新一代喜树碱衍生的抗癌临床试验候选物。
A series of novel 7-(N-substituted-methyl)-camptothecin derivatives was designed, synthesized, and evaluated for in vitro cytotoxicity against four human tumor cell lines, A-549, MDA-MB-231, KB, and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, with IC50 values ranging from 0.0023 to 1.11 μM, and were as or more potent than topotecan. Compounds 9d, 9e, and 9r exhibited the highest antiproliferative activity among all prepared derivatives. Furthermore, all of the compounds were more potent than paclitaxel against the multidrug-resistant (MDR) KBvin subline. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, compounds 9d, 9e, and 9r merit further development as a new generation of camptothecin-derived anticancer clinical trial candidates.