八角属Majucin型倍半萜内酯类化合物的神经营养活性研究

Neurodegenerative diseases (such as: AD、PD) are closely associated with the accelerating population aging, resulting in serious human's physical and mental problem. It becomes important to search the effective drug to treat these diseases. Majucin type sesquiterpene lactones are a series of natural products derived from genus illicium linn with special structures and remarkable neurotrophic activity. These products are mainly used for the reparative therapy of brain cells in neurodegenerative disease and brain damage. Previously, we found that the fruit of jiadifengpi, derived from genus illicium linn, was rich of Majucin type sesquiterpene lactones and we also isolated a compound from this plant with high yield and noteworthy neurotrophic activity. The current study is designed to conduct detail chemical composition research from two genus illicium linn plants (L. majus and L. micranthum), further perform structural modification of the lead compound and explore structure-activity relationship of these compounds. We are hoping to discover a novel series of compound with high drug-promising quality, which have the great significance to the research of innovative drugs and the development and utilization of genus illicium inn.

随着人口老龄化程度的加速，与年龄相关的神经退行性病变（如阿兹海默症、帕金森病等），对人类的身心健康的危害日趋严重，寻找其有效的治疗药物迫在眉睫。Majucin型倍半萜内酯类化合物是八角属植物中发现的一类结构独特，神经营养活性显著的天然产物，可用于保护脑细胞免受神经退行性疾病和脑损伤的恢复治疗。前期研究我们发现八角属植物假地枫皮果实中含有丰富的Majucin型倍半萜内酯类化合物，并分离得到了1个含量较高且具有显著神经营养活性的化合物。本项目拟在此基础上，通过活性追踪对二种八角属植物（大八角和小花八角）展开深入的活性成分研究，并对前期发现的有进一步研究价值的先导化合物进行结构修饰和改造，探讨该类化合物神经营养活性的构效关系，以期发现更具有成药性的神经营养活性化合物，这将对创新药物的研究以及八角属植物资源的开发利用具有重要意义。

随着人口老龄化程度的加速，与年龄相关的神经退行性病变（如阿兹海默症、帕金森病等），对人类的身心健康的危害日趋严重，寻找其有效的治疗药物迫在眉睫。Majucin型倍半萜内酯类化合物是八角属植物中发现的一类结构独特，神经营养活性显著的天然产物，有望用于保护脑细胞免受神经退行性疾病和脑损伤的恢复治疗。本项目对八角属含量较高的代表性化合物neomajucin、majucin、cycloparvifloralone、merrillianone进行了一系列的修饰，共合成化合物64个。发现引入2,4-己二烯酸片段的衍生物活性最强，说明2,4-己二烯酸结构在NGF诱导的PC12细胞神经突起生长的活性中对相应的底物具有进一步促进作用；对位卤素（F、Cl、Br）取代的苯丙酸与底物合成的化合物活性均强于间位卤素取代，这为进一步对四个底物进行结构修饰提供了依据。另外，本项目从八角属植物中大八角、假地枫皮和小花八角进行了分离鉴定共获得83个化合物，新化合物23个，2个为新骨架化合物，特别是大八角中发现的结构多样，含量丰富的二萜类化合物超出了我们的预想。本研究为八角属化学物质基础和综合开发应用提供了重要的参考依据。