鬼臼毒素衍生物的设计、合成及抗肿瘤活性评价  

Synthesis and antitumor activity of podophyllotoxin derivatives

作　　者：田丹丽[1] 梁春坡 罗刚 陈虹 TIAN Dan-li;LIANG Chun-po;LUO Gang;CHEN Hong(Tianjin First Central Hospital,Tianjin 300192,China;General Hospital of Tianjin Medical University,Tianjin 300052,China;Pharmacognosy Division,Medical College of Chinese People's Armed Police Force,Tianjin 300309,China)

机构地区：[1]天津市第一中心医院,天津300192 [2]天津医科大学总医院,天津300052 [3]武警后勤学院生药学教研室,天津300309

出　　处：《中国中药杂志》2019年第22期4874-4879,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30873363)

摘　　要：该文以鬼臼毒素或4’-去甲基表鬼臼毒素为先导化合物,通过药物设计拼合原理,以鬼臼毒素或4’-去甲基表鬼臼毒素和醛类化合物为起始原料,设计合成了一系列含亚胺结构的鬼臼毒素衍生物,以期望得到高效低毒的抗肿瘤化合物。合成了9个目标化合物6a^6i,其结构经^1H-NMR,HR-ESI-MS及熔点测定分析确证。以依托泊苷为阳性对照,采用MTT法考察了9个目标化合物对人宫颈癌细胞HeLa细胞的生长抑制活性。结果表明目标化合物6b,6d,6e,6f,6g,6i的生长抑制活性均优于阳性对照药VP-16,对进一步开展鬼臼毒素的结构改造和抗肿瘤活性研究具有一定的参考价值,值得深入研究。According to drug design flattening principle and using podophyllotoxin or 4’-demethylepipodophyllotoxin and aldehydes as starting material,a series of podophyllotoxin derivatives containing an imine structure with low toxicity were highly effective synthesized.Nine target compounds were successfully synthesized,and their structures were confirmed by^1H-NMR,HR-ESI-MS and melting point data analysis.Using etoposide as positive control drug,nine target compounds were screened for cytotoxicity against He La cells in vitro by MTT method.The antitumor activity screening results showed that compound 6 b,6 d,6 e,6 f,6 g,6 i exhibited higher inhibitory rate against He La cells than those of control drug VP-16.It provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.

关 键 词：鬼臼毒素 4’-去甲基表鬼臼毒素 抗肿瘤活性 构效关系 

分 类 号：R28[医药卫生—中药学]