DBAH-Tf靶向药物及其对乳腺癌细胞的杀伤作用分析  

Effects of 4-(12-Dihydroartemisininoxy) Benzoic Acid Hydrozidetransferrin Targeted Drug on Human Breast Cancer Cells

作　　者：谢伟玲[1] 杨培慧[1] 曾鑫[1] 蔡继业[1] 

机构地区：[1]暨南大学化学系,广州510632

出　　处：《分析化学》2009年第5期671-675,共5页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金(No.60578025);广州市科技计划项目基金(No.2003Z3-D2401)资助项目

摘　　要：以转铁蛋白(Tf)为靶向载体,与双氢青蒿素(DHA)化学偶联制备一种新的双氢青蒿素衍生物-转铁蛋白靶向药物。以DHA为原料先合成了12β-对甲酰肼苯基双氢青蒿素(DBAH),并采用紫外、红外、核磁共振及电化学等手段对目标产物的结构进行了表征。利用高碘酸钠氧化Tf的C端的N-糖链上的邻位羟基,其氧化产物和DBAH通过希夫碱偶联合成了DBAH-Tf靶向药物,采用紫外吸收光谱法和电化学方法进行表征。四甲基氮唑蓝法(MTT)分析了DBAH-Tf及DHA对人乳腺癌细胞(MCF-7)和正常乳腺细胞的体外杀伤作用,结果表明,DBAH-Tf对MCF-7的杀伤作用是正常乳腺癌细胞的286倍,体现出良好的靶向性。As target-carrier, transferrin（Tf） was conjugated with dihydroartemisinin （DHA） to form a new targeted drug. An analog of artemisinin, 4-（12-dihydroartemisininoxy） benzoic acid hydrazide （DBAH） have been synthesized and characterized by UV/vis absorption spectroscopy, IR spectroscopy, NMR, electroanalytic chemistry. Periodate was used to oxidize hydroxide group on the N-glycoside chains of C-domain, and then DBAH was reacted with the oxidized transferrin to form a covalent conjugate. In addition, this targeted drug was characterized by ultraviolet spectroscopy and electroanalytic chemistry. Methyl thiazolyl tetrazolium （MTT） assay was used to evaluate the killing effect of DBAH-Tf on MCF-7 and human normal breast cells. The results showed that DBAH-Tf was 286 times more potent in killing MCF-7 cancer cells than normal cells, which implied that DBAH-Tf could target to cancer cells.

关 键 词：双氢青蒿素衍生物 转铁蛋白 乳腺癌细胞 

分 类 号：R737.9[医药卫生—肿瘤]