肝靶向马蹄金素衍生物的合成及抗乙肝病毒活性研究

Synthesis and anti-HBV activity of hepatic targeting derivatives of Matijin-Su

目的合成具有肝靶向的马蹄金素衍生物,提高该类衍生物的肝脏药物浓度,增强其抗HBV活性。方法以二缩三乙二醇为连接臂,通过间接连接的方式将具有肝靶向性的半乳糖基与马蹄金素衍生物进行连接,并对所合成目标化合物进行体外抗HBV活性测试。结果合成了6个具有肝靶向潜力马蹄金素衍生物,活性测试结果显示所得目标产物均有不同程度的抗HBV活性,有3个化合物在高浓度(50μg·m L-1)下具有较高的抑制率,分别为15d(47.41%)、15e(48.58%)、15f(56.41%)。结论其中15f显示出较强的抗HBV活性,具有进一步研究开发的价值。

Abstract： Objective To improve the concentration in the liver lesion tissue and increase the anti-hepatitis B virus （HBV） activity by synthesing hepatic targeting derivatives of Matijin-Su （MTS）. Methods A series of hepatic tar- geting derivatives of MTS were synthesized by indirectly connecting the liver targeting galactose ligands to MTS using triethylene glycol as a linker, and their anti-HBV activities were evaluated in HepG2 2.2.15 cells. Results Six hepatic targeting derivatives of MTS were synthesized and 3 of these compounds exhibited high inhibition rate at 50 μg·mL-1： 15d （47.41%）, 15e （48.58%）, and 15f （56.41%）. Conclusion Derivative 15f shows potent anti- HBV activity with 56.41% inhibition rate anti-HBV activity at 50μg·mL-1 and is worthy of further research.