白杨素甘氨酸类化合物的合成及抗癌活性  

Syntheses and Anticancer Activities of Glycine Derivatives of Chrysin

作　　者：宋秀道[1] 何军 马锦[1] 刘运美[1] 郑兴[1] 雷小勇[1] 郭玉[1] 

机构地区：[1]南华大学药物药理研究所、湖南省药物蛋白质组学重点实验室 [2]化学化工学院,衡阳421001

出　　处：《高等学校化学学报》2014年第7期1465-1470,共6页Chemical Journal of Chinese Universities

基　　金：湖南省重点学科建设项目(批准号:湘教发[2011]76);南华大学研究生创新基金(批准号:2012XCX12)资助~~

摘　　要：以白杨素为起始原料，通过卤代和水解反应制得中间产物7-O-羧烷基化的白杨素衍生物（6～9）；然后以1-乙基-3-（3-二甲氨基丙基）碳二亚胺（EDCI）、1-羟基苯并三氮唑（HOBt）和4-二甲氨基吡啶（DMAP）为催化体系，4个中间产物分别与甘氨酸甲酯盐酸盐进行酰胺缩合反应，制得白杨素甘氨酸甲酯类化合物12～15；化合物1．2—15在pH=10—11和室温下水解得到相应的白杨素甘氨酸类化合物（16～19）．所有目标化合物的结构均经1HNMR，13CNMR，IR以及MS确认．以顺铂为阳性对照药物，采用噻唑蓝比色（MT＇F）法检测了目标化合物对人肝癌细胞HepG2和人胃癌细胞MGC-803的体外增殖抑制作用．结果表明，目标化合物14～16，18和19的体外抗肿瘤活性明显强于白杨素，且化合物18（IC50=4．36μmol／L）对MGC-803细胞的增殖抑制作用强于阳性药物顺铂（IC50=4．40μmol／L）．In order to obtain novel lead compounds with high efficacy, low toxicity and minimum of side effects, using chrysin（5,7-dihydroxyflavone） with very broad biological activities as a starting material, four intermediates 7-O-carboxyalkylation chrysin derivatives （6--9） were synthesized by halogenation and hydroly- sis. Four glycine methyl ester derivatives containing chrysin（12--15） were synthesized when the four intermediates above condensated with glycine methyl ester hydrochloride using 1-ethyl-3-（3-dimethylaminopropyl） carbodiimide hydrochloride （ EDCI）, N-hydroxybenzotriazole （HOBt） and 4-dimethylamiopryidine （DMAP） as a coupling reagent. And then the corresponding glycine derivatives of chrysin （16--19） were obtained by hydrolysis under conditions of room temperature and pH 10--11. The structures of the target compounds were assigned by 1H NMR, 13C NMR, IR and MS. Taking cisplatin as a reference substance, the in vitro antitumor activity tests for target compounds against human hepatocellular carcinoma HepG2 cells and gastric carcinoma MGC-803 cells were carried out by MTT method. The results of primary pharmacological tests indicated that five compounds （14--16, 18, 19） possessed the more potent antitumor activity than chrysin in vitro. What＇ s more, the antitumor activity of compound 18（ IC50 =4. 36 μmo]/L） against MGC-803 cells was better than the positive reference compound cisplatin（ IC50 =4. 40 μmol/L）.

关 键 词：白杨素 衍生物 甘氨酸 抗肿瘤 

分 类 号：O629.9[理学—有机化学] R914.5[理学—化学]