新型酰胺类鬼臼毒素衍生物的合成及体外抗肿瘤活性  

Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents

作　　者：孙强稳 王杰[1] 陈守强[1] 牛聪[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]武警后勤学院生药学教研室,天津300309

出　　处：《天津医科大学学报》2015年第4期282-286,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基金资助(08JCYBJC070000)

摘　　要：目的:通过对鬼臼毒素母核进行结构改造,以获得高效、低毒、抗多药耐药的新型鬼臼毒素衍生物。方法:将4β-氨基-4-脱氧表鬼臼毒素的C-4位经酰胺化分别引入对位取代的苯甲酸和对位取代的肉桂酸化合物,得到4-甲酰基苯甲酸及4-甲酰基肉桂酸的鬼臼毒素类衍生物,通过MTT法筛选,并对K562和Hela细胞进行药理活性评价。结果:合成得到两个系列共8个化合物,所有化合物都经过HR-ESI-MS和1HNMR验证,其中化合物1d、2b具有较强的体外抗肿瘤活性。结论:在C-4位引入4-甲酰基苯甲酸以及4-甲酰基肉桂酸基团可增加鬼臼毒素类衍生物的抗肿瘤活性。Objective：To obtain novel podophyllotoxin derivatives with higher efficiency, lower toxicity and anti-multi-drug resistance. Methods：Derivatives of 4-formyl benzoicacid and 4-formyl-cinnamic acid in C-4 position of 4β-amino-pipodophyllotoxin were introduced;Hela cells and K562 were used to evaluate pharmacological activity in vitro. Results：Eight compounds by different methods were obtained, and all compounds were confirmed by MS and 1HNMR validation. The compounds 1b,1d,2a and 2b had a good drug resistance in both Hela and K562 cell line. Conclusion：At C-4 position, podophyllotoxin introduced 4-formyl-benzoyl derivatives and 4-formyl-cinnamic acid derivatives can increase antitumor activities.

关 键 词：鬼臼毒素衍生物 苯甲酸 肉桂酸 体外抗肿瘤活性 

分 类 号：R9[医药卫生—药学]