含芳杂环取代的马蹄金素衍生物的设计、合成及抗乙肝病毒活性

Synthesis and anti-HBV activity evaluation of Matijin-Su derivatives with aromatic heterocycles

摘要: 以马蹄金素(MTS)为先导化合物，设计、合成了11个新的含芳杂环取代的马蹄金素衍生物，其结构经NMR、ESI-MS确认。采用HepG2 2.2.15细胞为乙肝病毒载体，评价目标化合物的抗HBV活性。结果表明，化合物 7a ［IC₅₀=2.94 μmol/L，选择指数(SI)=146.39］和 9a (IC₅₀=2.21 μmol/L，SI>；250)对HBV DNA复制的抑制活性高于先导化合物MTS(IC₅₀=11.16 μmol/L，SI=10.78)，且具有更高的SI，提示该化合物在治疗HBV感染时具有更高的安全性，具有潜在的研究开发价值。

Abstract: Hepatitis B virus(HBV)-infected hepatitis is one of the most common infectious disease worldwide. To find novel effective anti-HBV agents, a series of Matijin-Su(MTS)derivatives with aromatic heterocycles were synthesized and evaluated for their anti- HBV activities in HepG2 2. 2. 15 cells. Among them, compounds 7a( IC₅₀=2. 94 μmol/L)and 9a( IC₅₀=2. 21 μmol/L)exhibited more potent inhibitory activity against the replication of HBV DNA in HepG2 2. 2. 15 cells than that of lead compound MTS(IC₅₀=11. 16 μmol/L). Notably, both 7a and 9a displayed a high selective index(SI)of 146. 39 and > 250, respectively, which were also much higher than that of MTS(SI=10. 78). Therefore, compounds 7a and 9a may be promising anti-HBV agents with safety profile for HBV infection.