鬼臼毒素五元氮杂环类衍生物的合成及细胞毒活性研究有机化学.pdfVIP

DOI: 10.6023/cjoc201312029 研究论文 有机化学 Chinese Journal of Organic Chemistry ARTICLE 鬼臼毒素五元氮杂环类衍生物的合成及细胞毒活性研究 朱培芳a 赵静峰*,b 羊晓东b 张洪彬b (a 云南中医学院实验中心 昆明 650500) (b 云南大学教育部自然资源药物化学重点实验室 昆明 650091) 摘要 从鬼臼毒素出发, 通过简洁的合成路线合成了 9 个新型的鬼臼毒素五元氮杂环类衍生物, 其结构经 1H NMR, 13C NMR, IR, HR-ESI-MS 以及 X 单晶衍射确定. 对合成的新化合物进行了体外抗肿瘤活性的筛选, 结果表明, 化合物 10 具有较好的细胞毒活性, IC50 值为 2.63～4.73 μmol/L, 对 4 种细胞株的活性均优于顺铂, 可以作为先导化合物作进一步 的结构修饰和更深入的活性研究. 关键词 鬼臼毒素; 五元氮杂环; 结构改造; 细胞毒活性 Synthesis and Cytotoxic Activity of Podophyllotoxin Five-Membered N-Heterocyclic Derivatives Zhu, Peifanga Zhao, Jingfeng*,b Yang, Xiaodongb Zhang, Hongbinb a ( Experimental Center, Yunnan University of Traditional Chinese Medicine, Kunming 650500) b ( Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of Education, Yunnan University, Kunming 650091) Abstract Nine novel podophyllotoxin five-membered N-heterocyclic derivatives have been prepared from commercially podophyllotoxin. Their structures were confirmed by 1H NMR, 13C NMR, IR, HR-ESI-MS and X-ray crystallographic analy- sis. These derivatives have been evaluated in vitro against a panel of human tumor cell lines. Compound 10 (IC50: 2.63～4.73 μmol/L) showed superior cytotoxic activity compared with DDP (a clinically available anticancer drug) in four human tumor cell lines investigation, which is to be a lead compound for further structural modifications and activity research. Keywords podophyl