吡喃半乳糖糖基化马蹄金素衍生物的合成及抗乙肝病毒活性研究  

Synthesis and Anti-Hepatitis B Virus Activities of Galactopyranosyl Derivatives of Matijin-Su

作　　者：徐广灿[1,2] 刘青川[3] 袁洁[1,4] 胡占兴[1] 马芳芳[1,2] 梁光义[1,2] 徐必学[1] 

机构地区：[1]贵州省中国科学院天然产物化学重点实验室,贵阳550002 [2]贵阳中医学院,贵阳550002 [3]中国人民解放军第三○二医院,北京100039 [4]贵州大学药学院,贵阳550002

出　　处：《有机化学》2016年第7期1617-1625,共9页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.81360472);西部之光人才(2014年)资助项目

摘　　要：为提高马蹄金素(MTS)衍生物的肝脏药物浓度,增强其抗乙型肝炎病毒(HBV)活性.通过以乙醇胺为连接臂将具有肝靶向性的半乳糖配基与MTS进行间接连接,设计合成了5个肝靶向MTS衍生物,通过~1H NMR,^(13)C NMR,~1H-~1H COSY,HMQC和ESI-MS对其进行了结构表征,并用Hep G2 2.2.15细胞模型初步评价了合成所得目标化合物的抗乙肝病毒活性.结果表明,所有目标化合物对HBV DNA的复制均有抑制作用,且具有一定的量效关系.To improve the concentration in liver lesion tissue and increase the anti-hepatitis B virus （HBV） activities of Matijin-Su （MTS） derivatives, five hepatic targeting galactopyranosyl derivatives of MTS were synthesized by indirect connecting the liver targeting galactose ligands to MTS using ethanolamin as a linker and their structures were confirmed by 1^H NMR, 13^CNMR, 1^H-IH COSY, HMQC and ESI-MS. The anti-HBV activities of those compounds were evaluated in HepG2 2.2.15 cells. The screening results showed that all target compounds had inhibitory effect on HBV DNA replication in HepG2 2.2.15 cells in a dose-response manner.

关 键 词：肝靶向 马蹄金素衍生物 半乳糖 抗HBV活性 

分 类 号：O621.3[理学—有机化学] TQ460.1[理学—化学]