“一瓶法”合成鬼臼毒素类似物及其体外抗肿瘤活性  

One-pot syntheses of podophyllotoxin analogues and their antitumor activities in vitro

作　　者：于鹏飞[1] 陈虹[2] 何春娴[1] 王晶[2] 李敏[2] 雷志勇[2] 程卯生[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]中国人民武装警察部队医学院医技药学系,天津300162

出　　处：《中国药物化学杂志》2008年第1期32-34,共3页Chinese Journal of Medicinal Chemistry

基　　金：天津市应用基础重点项目(06YFJZJCO2700);中国人民武装警察部队总部科研基金项目(WKH2005-6)

摘　　要：目的探讨天然产物鬼臼毒素类似物表鬼臼毒素(1)和4′-脱甲基表鬼臼毒素(2)的简易合成方法,并测试其体外抗肿瘤活性。方法采用"一瓶法"合成目标产物,并通过MTT法和SRB法测定2个目标化合物的体外抗肿瘤活性。结果与结论通过对鬼臼毒素进行结构改造,得到合成其衍生物的常见化学反应的简易操作方法,化合物1和2的收率分别为86%和79%,其结构经1H-NMR和ESI-MS谱确证。活性测试结果表明,目标化合物对4种肿瘤细胞(HeLa细胞、SKOV3细胞、K562细胞、耐阿霉素K562细胞)均具有较强的活性。Aim To study simple synthesis methods of epipodophyllotoxin（1） and 4＇-demethylepipodophyllotoxin（ 2 ） and to test their antitumor activities in vitro. Methods The target compounds were prepared by employing one-pot method, and their antitumor activities were evaluated by the standard MTT or SRB assay. Results and conclusion Simple methods to the derivatives of natural product podophyllotoxin were gained, and the overall yields of the two compounds were 86 % and 79 % respectively. Their structures were confirmed by 1H-NMR and ESI-MS. The pharmacological evaluation results showed that the target compounds presented bloactivities to the HeLa, SKOV3, K562, and adriamycin resistant K562 cell lines.

关 键 词：“一瓶法” 鬼臼毒素 表鬼臼毒素 4’-脱甲基表鬼臼毒素 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]