熊果酸半乳糖苷偶联物的合成及保肝活性

Synthesis and Hepatoprotective Activity of Glycoside Conjugates of Ursolic Acid

通过改进的Koenigs-knorr法在熊果酸3位和28位进行半乳糖苷化得到6个化合物.通过MTT法考察了上述化合物对大鼠肝干细胞样上皮细胞WB-F344的作用,发现化合物12b和12e可明显提高WB-F344细胞的成活率.体内实验结果表明,化合物12b,12d和12f在刀豆蛋白引起的小鼠急性免疫性肝损伤模型上,除化合物12d对小鼠血清谷草转氨酶升高具有一定程度的降低作用外,其余化合物均未见对谷草和谷丙转氨酶的升高表现出明显的保护作用.

Ursolic acid was reported that it could be used for liver protection. However, its usage is restricted by its poor solubility in water. To improve the hepatoprotective activity of ursolic acid, some novel derivatives of ursolic were designed and synthesized. By modified Koenigs-knorr method, six glycoside conjugates of ursolic acid with modification at C3 and/or C28 were synthesized. It was found that compounds 12b and 12e could obviously increase the survival rate of WB-F344 rat hepatic stem-like epithelial cells evaluated through MTT method at cellular level. In vivo, however, it was not found that compounds 12b, 12d and 12f could obviously prevent the rise of the level of serum transaminases induced by ConA in a mice acute immunity liver damage model except that compound 12d could reduce the level of aspartate aminotransferase（AST） to some extent. By the introduction of galactose moieties, the liver protection potency of ursolic acid was improved.