Macrocyclic Diterpenoids from Euphorbia peplus Possessing Activity Towards Autophagic Flux

来自大戟属植物的具有自噬通量活性的环状二萜类化合物

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Abstract

Euphjatrophanes H-L (1-5), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from Euphorbia peplus, along with eight known diterpenoids (6-13). 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 1-3, 5-10, and 12 significantly increase autophagic flux, and compounds 1 and 12 displayed relatively high BBB permeability, with logPe values of -4.853 and -5.017, respectively. These findings indicated that jatrophane diterpenoids could serve as a valuable source for innovative autophagy inducers.

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