鬼臼毒素衍生物的合成及其体外抗肿瘤活性  

Synthesis of podophyllotoxin derivatives and their antitumor activity in vitro

作　　者：赵明[1,2] 张元[2] 杨再鑫[2] 曹波[2] 郑奕[2] 陈虹[1,2,3] 

机构地区：[1]天津医科大学研究生院,天津300070 [2]中国人民武装警察部队医学院生药教研室,天津300162 [3]天津市职业与环境危害生物标志物重点实验室,天津300162

出　　处：《中国药物化学杂志》2009年第2期85-88,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(30873363);天津市应用基础重点项目(06YFJZJCO2700);天津市应用基础项目(08JCYBJC070000)

摘　　要：目的获得更高活性且具有抗多药耐药活性的抗肿瘤新化合物。方法将4β-氨基-4-脱氧鬼臼毒素与醇类化合物以丁二酸为桥连接合成了7个鬼臼毒素衍生物,其结构经1H-NMR、TOF-MS证实。采用K562和K562/AO2细胞经MTT法对目标化合物进行体外抗肿瘤活性筛选。结果7个化合物均为新化合物,其中5b、5d的抗肿瘤活性显著高于VP-16,并且5b、5c、5d、5e的抗多药耐药活性显著高于VP-16。结论合成的鬼臼毒素衍生物的抗肿瘤活性与阳性对照药VP-16相比均有所提高。Aim To find compounds with superior antitumor bioactivity and overcoming multidrug resistance. Methods Seven derivatives of podophyllotoxin were synthesized by linking 4β-amino-4-deoxypodophyllotoxin with alcohols through succinic acid. Their structures were confirmed by ^1H-NMR, TOF-MS. Their antitumot activity was tested by MTT method against K562 and K562/AO2 in vitro. Results Seven derivatives were not reported by previous literature. The derivatives 5b,Sd exhibit superior anticancer activity compared to VP-16 against K562 in vitro. The derivatives 5b,5c,Sd and 5e may overcome MDR compared to VP-16 against K562/AO2 in vitro. Conclusion The results indicate that these compounds show high antitumor activity.

关 键 词：构效关系 化学合成 鬼臼毒素衍生物 抗肿瘤 多药耐药 

分 类 号：R914[医药卫生—药物化学]