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具有自噬流活性的大环二萜类化合物。

Macrocyclic Diterpenoids from Possessing Activity Towards Autophagic Flux.

作者信息

Chen Lu, Liu Lulan, Li Yingyao, Guan Shipeng, Fan Lingling, Qin Xujie, Di Yingtong, Tang Lei, Luo Rongcan, Yan Ying

机构信息

State Key Laboratory of Functions and Applications of Medicinal Plants & College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 550014, China.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.

出版信息

Int J Mol Sci. 2024 Dec 31;26(1):299. doi: 10.3390/ijms26010299.

Abstract

Euphjatrophanes H-L (-), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from , along with eight known diterpenoids (-). Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments. All compounds were subjected to bioactivity evaluation using flow cytometry in autophagic flux assays with HM mCherry-GFP-LC3 cells, the human microglia cells which stably expressed the tandem monomeric mCherry-GFP-tagged LC3. Compounds -, -, and significantly increase autophagic flux, and compounds and displayed relatively high BBB permeability, with log values of -4.853 and -5.017, respectively. These findings indicated that jatrophane diterpenoids could serve as a valuable source for innovative autophagy inducers.

摘要

从[具体来源]中分离出了四种新的麻风树烷型二萜和一种新的山黧豆烷型二萜——喜树欧瑞烷H-L(-),以及八种已知的二萜(-)。它们的结构是通过广泛的光谱分析和X射线晶体学实验确定的。使用稳定表达串联单体mCherry-GFP标记的LC3的人小胶质细胞HM mCherry-GFP-LC3,通过流式细胞术在自噬通量测定中对所有化合物进行生物活性评估。化合物-、-和显著增加自噬通量,化合物和表现出相对较高的血脑屏障通透性,log值分别为-4.853和-5.017。这些发现表明,麻风树烷二萜可作为创新自噬诱导剂的宝贵来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8492/11719499/dbadbd8c1b5e/ijms-26-00299-g001.jpg

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