异丙酰基为桥合成白杨素氨基酸衍生物及其抗癌活性研究  

Anti-tumor Activity of Chrysin Amino Acids Derivatives Bridged by Isopropionyl

作　　者：刘容芳 何军[2] 沈洪秀[1] 刘鼎[1] 李洋[1] 郑兴[1] 唐国涛[1] 郭玉[1] 刘运美[1] 

机构地区：[1]南华大学药物药理研究所,湖南衡阳421001 [2]南华大学化学化工学院,湖南衡阳421001

出　　处：《肿瘤药学》2017年第4期395-400,411,共7页Anti-Tumor Pharmacy

基　　金：湖南省研究生科研创新项目(CX2016B470);湖南省教育厅一般项目(14C1003);南华大学分子靶标新药协同创新中心基金项目

摘　　要：目的为改善天然产物白杨素的活性,利用氨基酸类物质特性,以异丙酰基为桥合成一系列白杨素氨基酸类衍生物,以期得到活性更高的衍生物。方法采用烷基化、水解、酰胺缩合等药物合成方法在白杨素的7位引入不同类型的氨基酸,得到一系列衍生物,运用~1H-NMR和^(13)C-NMR等方法对其结构进行确证;采用MTT法,以白杨素母体、5-FU为对照,检测其抗人肝癌细胞HepG2和人乳腺癌细胞MCF-7活性。结果 ~1H-NMR和^(13)C-NMR等数据显示,烷酰基、氨基酸等基团被成功地引入到白杨素分子的7位。活性测试结果显示,化合物2,5b,5d抑制HepG2细胞的IC_(50)值低于母体化合物白杨素,化合物2,3,4b,4c,4d,5a和5c抑制MCF-7细胞的IC_(50)值低于白杨素。结论通过实验能成功地将烷酰基、氨基酸等基团引入白杨素的7位,且得到的大多数衍生物,相较于天然产物白杨素母体,具有更好的抗人肝癌细胞HepG2和人乳腺癌细胞MCF-7的活性。Objective In order to improve the anti-tumor activity of natural product chrysin, we have synthesized a series of chrysin amino acid derivatives in a bridge of isopropionyl with amino acids, which were expected to obtain derivatives with higher activity. Methods The basic methods of synthesis including alkylation, hydrolysis and amide condensation were used to introduce different amino acids into C7 position of chrysin. A series of chrysin derivatives was characterized with 1H-NMR and 13C-NMR. The MTY assay was used to evaluate the anti-proliferative activity of these chrysin derivatives, chrysin and 5-fluorouracil aganist human hepatocellular carcinoma ceils HepG2 and human breast cancer cells MCF-7. Results The result of 1H-NMR and 13C-NMR indicated that alkanoyl and amino acids were successfully introduced into C7 position of chrysin. The MTr assay suggested that half maximal inhibitory concentrations （ICs0） of compounds 2, 5b, and 5d were lower than the parent compound chrysin against human hepatocellular carcinoma cell line HepG2. Compounds 2, 3, 4b, 4c, 4d, 5a and 5c have lower ICs0 values than chrysin against human breast cancer cell line MCF-7. Conclusions Alkanoyl and amino acids groups were successfully introduced into the C7 position of the chrysin. And most of these derivatives have displayed better antitumor activities than chrysin against human hepatocellular carcinoma cell line HepG2 and human breast cell line MCF-7.

关 键 词：白杨素 氨基酸 抗癌 

分 类 号：R962[医药卫生—药理学]