齐墩果酸γ-内酯衍生物的合成及活性评价

Synthesis and Biological Evaluation of Oleanane Triterpenoid with γ-Lactone Functionality in Ring C

对齐墩果酸(OA)的C环进行结构修饰,合成了含有γ-内酯结构的OA衍生物,并针对12个常见疾病的蛋白质靶点或细胞进行了体外生物活性筛选.其中部分化合物结构中引入了水溶性基团,如形成糖苷或引入酸性基团,提高了生物利用度.活性筛选结果表明,内酯化合物13对组织蛋白酶K显示出很好的抑制活性(IC50=3.58μg/mL),可作为抗骨质疏松药物的先导化合物.初步构效关系分析表明,该化合物的γ-内酯结构和糖链片段为活性基团.

Some oleanolic acid（OA） derivatives with γ-lactone functionality in ring C had better H 2O solubi-lity and bioavailability than OA.Preliminary biological screening in vitro of these derivatives for 12 responding protein targets and cells of frequent diseases was processed. This investigation revealed that lactone 13 showed significant activity（IC 50=3.58 μg/mL） against Cathepsin K,and was found to be a potent leader compound for the treatment of osteoporosis.Preliminary structure-activity relationship analysis indicated that the γ-lactone and glyco-groups were active groups.