Macrocyclic Diterpenoids from Euphorbia peplus Possessing Activity Towards Autophagic Flux

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