马蹄金素类似物的合成及其初步抗HBV活性研究

Synthesis and anti-hepatitis B virus activity of Matijin-Su analogues

目的合成马蹄金素[N-(N-苯甲酰基-L-苯丙氨酰基)-O-乙酰基-L-苯丙氨醇,MTS]的类似物,以期寻找高效低毒的抗乙肝病毒化合物。方法以L-苯丙氨酸为起始原料,通过磺酰化、酰化、水解、烷基化等反应,合成马蹄金素类似物并对其进行体外抗乙肝病毒活性测试。结果合成了7个具有磺酰胺结构片段的马蹄金素类似物,活性测试结果显示所有的目标产物均有不同程度的抗乙肝病毒活性,有3个化合物在8μg·mL-1的浓度下具有较高的抑制率,分别为2b(41.9%)、2d(61.3%)、3(47.5%)。结论其中2d显示出较强的抗HBV活性,在3.2μg·mL-1时抑制率也有50.9%,具有进一步研究开发的价值。

Objective To find new anti-hepatitis B virus （HBV） compounds with high activity and low toxicity from Matijin-Su [N-（N-benzoyl-L-phenylalanyl）-O-acetyl-L-phenylalanol] （MTS）. Methods A series of MTS analogues were synthesized by sulfonamide, acylation, hydrolysis, alkylation reactions and their anti-HBV activity evaluated in HepG2 2.2.15 cells. Results Seven analogues with sulfonamide structure of MTS were synthesized and 3 of these com- pounds exhibited high inhibition rate at 8μg · mL - 12b （41.9%）, 2d （61.3%） and 3 （47.5%）. Conclusion The ana- logues of 2d have potent anti-HBV activity, which shows 50.9% of inhibition rate anti-HBV activity at 3.2 μg ·mL 1 and is worthy of further research.