全新结构吲哚类生物碱的合成及降甘油三酯活性研究

Synthesis and evaluation on triglyceride inhibitory activities of novel indole alkaloids

摘要: 本研究首次合成3个三环6，5，7和6个四环6，5，5，5两类全新结构的吲哚类生物碱，评价了它们抑制甘油三酯活性，其中，化合物4c活性最优，IC₅₀值为6.35 μmol·L^-1，且在细胞水平具有较好的安全性。初步作用机制显示4c可能是通过激活腺苷酸激活蛋白激酶adenosine 5'-monophosphate（AMP）-activated protein kinase，AMPK增加细胞内脂质代谢。研究结果为寻找抗非酒精性脂肪肝（non-alcoholic fatty liver disease，NAFLD）化合物提供了一类全新的先导化合物。

Abstract: Three tricyclic6,5,7 and six tetracyclic6,5,5,5 novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC₅₀ value of 6.35 μmol·L^-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.