马蹄金素衍生物的合成及抗乙肝病毒活性

邱净英; 黄正明; 潘卫东; 曹佩雪; 梁光义

马蹄金素衍生物的合成及抗乙肝病毒活性

Synthesis and anti-hepatitis B virus activities of Matijin-Su derivatives

摘要

摘要: 以化合物马蹄金素N-(N-苯甲酰基-L-苯丙氨酰基)-O-乙酰基-L-苯丙氨醇,MTS为先导化合物，设计并合成了10个马蹄金素衍生物，所有化合物均为新化合物，其结构经NMR、ESI-MS确认。以HepG2 2.2.15细胞为乙肝病毒载体，对合成的马蹄金素衍生物进行了抗乙肝病毒活性测试。结果表明，在测试浓度范围内，化合物 5e (IC₅₀:10.67 μmol/L,SI:47.26)、 4c (IC₅₀:11.09 μmol/L,SI:15.03)、 4b (IC₅₀:19.75 μmol/L,SI:4.74)、 5b (IC₅₀:59.55 μmol/L,SI:3.00)和 5a (IC₅₀:77.69 μmol/L,SI:5.81)对乙肝病毒DNA复制的抑制活性高于阳性对照药物拉米夫定(IC₅₀:82.42 μmol/L,SI:41.59)。其中，化合物 5e (IC₅₀:10.67 μmol/L,SI:47.26)的抑制活性最强，选择指数较高，具有进一步研究开发的价值。

Abstract: A series of Matijin-Su MTS,N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol derivatives were synthesized and evaluated for their abilities to inhibit the replication of hepatitis B virus(HBV) DNA in HepG2 2.2.15 cells.Compounds 5e (IC₅₀:10.67 μmol/L,SI:47.26), 4c (IC₅₀:11.09 μmol/L,SI:15.03), 4b (IC₅₀:19.75 μmol/L,SI:4.74), 5b (IC₅₀:59.55 μmol/L,SI:3.00) and 5a (IC₅₀:77.69 μmol/L,SI:5.81) exhibited significant inhibitory activity against the replication of HBV DNA in HepG2 2.2.15 cells,and were more potent than the positive control lamivudine(IC₅₀:82.42 μmol/L,SI:41.59).Compound 5e (IC₅₀:1.31 μmol/L,SI:326.31) showed the most potency in vitro anti-HBV activity within all the tested compounds,and could be a potent HBV inhibitor with high selectivity index.

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