摘要
以二缩三乙二醇或三缩四乙二醇为连接臂,通过间接引入具有肝靶向性的D-半乳糖配基的方法,设计合成了6个半乳糖糖基化修饰的肝靶向马蹄金素(MTS)衍生物;通过1H NMR,13C NMR,1H-1H COSY,HMQC和ESI-MS对其结构进行了表征;并以Hep G2 2.2.15为细胞模型初步评价了目标化合物的抗乙肝病毒(HBV)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.化合物15b的体外抗HBV活性最好,后期研究将选用其进行小鼠体内组织分布实验,并与原型化合物以及Y101体内组织分布情况进行比较研究,以验证半乳糖基的引入能否提高MTS衍生物的肝靶向性.
To explore the effect of the length of the linker on the activities of the derivatives of Matijin-Su（ MTS） with potential for hepatic targeting,six galactosyl derivatives of MTS with potential for hepatic targeting were synthesized by binding galactosyl to derivatives of MTS using triethylene glycol or tetraethylene glycol as a linking arm,and their structures were confirmed by means of1 H NMR,13 C NMR,1H-1H COSY,HMQC and ESI-MS. The anti-HBV activities of those compounds were evaluated using Hep G2 2. 2. 15 cells. The screening results showed that all the target compounds had inhibitory effect on HBV DNA replication in Hep G2 2. 2. 15 cells in a dose-response manner. The inhibition rates of compounds 15b（ 72. 24%）,15c（ 56. 49%）,15f（ 65. 24%） on the replication of HBV DNA were better than other tested compounds,when the in concentration of the drug was 50 μg/m L. The results can provide reference for further research of hepatic targeting MTS derivatives. For the evaluation of the hepatic target distribution of galactopyranosyl derivatives of MTS,compound 15 b with best anti HBV activity will be selected to do tissue distribution experiments in vivo and comparative study with derivative of MTS（ 13b） and Y101.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2016年第8期1451-1459,共9页
Chemical Journal of Chinese Universities
基金
国家自然科学基金(批准号:81360472)资助~~
关键词
肝靶向
半乳糖
马蹄金素衍生物
抗HBV活性
Hepatic targeting
Glacatose
Derivatives of Matijin-Su（MTS）
Anti-hepatitis B virus activity
