熊果酸氨基酸偶联物的合成及保肝活性

Synthesis and hepatoprotective activity of three amino acid conjugates of ursolic acid

目的设计合成熊果酸28位氨基酸偶联物并测定其保肝活性。方法以熊果酸为起始原料,首先将3位羟基进行酯保护2,8位羧基与保护的氨基酸反应,然后脱保护基,得到偶联物。利用肝细胞培养和小鼠急性肝损伤CCl4、ConA筛选模型分别测定偶联物的体外、体内保肝活性。结果与结论得到3个未见报道的化合物,其结构经核磁共振谱和质谱确定。水溶性测定结果显示3个偶联物的水溶性很低,保肝试验结果显示3个偶联物无明显的保肝活性。

Ursolic acid is a pentacyclic triterpenoid showing anticancer,anti-virus,anti-inflammatory,hepatoprotective and anti-microbial activities.In order to improve its water solubility so as to enhance its bioavailability,three amino acid conjugates of ursolic acid were designed and synthesized.Starting from ursolic acid,its 3-OH was protected by esterification first,and then 28-COOH reacted with the protected amino acid reagents.After deprotection,three targeted compounds,5a,5b and 5c,were obtained.These new compounds were characterized by various spectroscopic methods,including 1H-NMR,13C-NMR and ESI-MS.The in vitro and in vivo hepatoprotective activity was measured in GalN inducing hepatocyte injury model,and CCl4 and ConA inducing hepatocyte injury model,respectively.No apparent hepatoprotective activities were detected in both models.