鬼臼毒素脲类衍生物的合成和体外抗癌活性的研究  

Synthesis and biological evaluation of 4-ureido podophyllotoxin derivatives as anticancer agents

作　　者：李楠[1,2] 赵阳[1,2] 魏菲[3] 高晨光[2] 曹波[2] 高颖[2] 陈虹[1,2] 

机构地区：[1]天津医科大学药学院天津市临床药物关键技术重点实验室,天津300070 [2]中国人民武装警察部队后勤学院生药与药剂学教研室,天津300309 [3]天津中医药大学研究生院,天津300193

出　　处：《天津医科大学学报》2016年第3期199-203,共5页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(30873363);天津市应用基础项目资助(08JCYBJC070000)

摘　　要：目的:为了得到抗癌活性更高的抗肿瘤药物,设计、合成新型脲类鬼臼毒素衍生物。方法:以鬼臼毒素或4’-去甲基鬼臼毒素为起始原料经N,N’-羰基二咪唑(CDI)活化其C-4位氨基,并与仲胺类化合物进行缩合反应,得到鬼臼毒素脲类衍生物,经氢谱和高分辨质谱对其进行结构表征。采用噻唑蓝(MTT)法测试目标化合物对人白血病(K562)和人宫颈癌(Hela)细胞的体外抗肿瘤活性。结果:合成8个新的目标化合物,其中化合物6a增殖抑制活性较强。结论:在鬼臼毒素C-4位引入哌嗪环脲类结构可提高其体外抗肿瘤活性。Objective： To obtain anticancer agents with higher efficiency through a novel series of 4-ureido podophyllotoxin derivatives.Methods： The novel target compounds were synthesized by reacting podophyllotoxin or 4＇-demethylepipodophyllotoxin with secondary amines under catalytic agent N, N＇- carbonyldiimidazole（ CDI）. All the compounds were characterized by1H-NMR and HR-MS.Meanwhile, MTT assay was used to test their cytotoxicity against K562 and Hela cell lines. Results： Eight novel target compounds were synthesized. Among them, compound 6a exhibits was identified to have stronger inhibition effect. Conclusion： The anticancer activity of podophyllotoxin could be improved when its C-4 is combined with the structure of ureido and piperazidine.

关 键 词：鬼臼毒素 脲 N N’-羰基二咪唑 抗肿瘤活性 

分 类 号：R9[医药卫生—药学]