Macrocyclic diterpenoids from the seeds of Euphorbia peplus with potential activity in inducing lysosomal biogenesis

• Published in: Bioorganic chemistry Vol. 105; p. 104464
• Main Authors: Chen, Yan-Ni, Ding, Xiao, Lu, Qing-Yun, Li, Dong-Mei, Li, Bo-Ting, Liu, Shuai, Yang, Lei, Zhang, Yu, Di, Ying-Tong, Fang, Xin, Hao, Xiao-Jiang
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.12.2020; Elsevier
• Subjects: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - metabolism; Drug Evaluation, Preclinical; Drugs, Chinese Herbal - chemistry; Euphoperfoliane; Euphorbia - classification; Euphorbia peplus; HeLa Cells; Humans; Lathyrane; Life Sciences & Biomedicine; Lysosomal biogenesis activity; Lysosomes - drug effects; Macrocyclic Compounds - isolation & purification; Macrocyclic Compounds - metabolism; Macrocyclic diterpenoid; Molecular Structure; Organelle Biogenesis; Physical Sciences; Plant Extracts - isolation & purification; Plant Extracts - metabolism; Science & Technology; Seeds - chemistry; Macrocyclic diterpenoid; Lathyrane; Euphoperfoliane; Euphorbia peplus; Lysosomal biogenesis activity; JATROPHANE DITERPENOIDS; ESTERS
• DOI: 10.1016/j.bioorg.2020.104464
• ISSN: 0045-2068

[Display omitted] •Five new diterpenoids were isolated from the seeds of Euphorbia peplus.•Compounds 1–3 feature a very rare euphoperfoliane 5/11/5-tricyclic skeleton.•Compounds 1 &3 can significantly induce lysosomal biogenesis by activation of TFEB. The first phytochemical investigation of the seeds of Euphorbia peplus led to the isolation and characterization of five new (1–5), named euphopepluanones A–E, and five known diterpenoids (6–10). Their structures were established by extensive spectroscopic analysis and X-ray crystallographic experiments. Euphopepluanones A–E (1–3) feature a very rare 5/11/5-tricyclic skeleton, and euphopepluanones D–E (4–5) represent the first report of lathyrane type diterpenoids found in E. peplus. The new compounds 1–5 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining, in which compounds 1 and 3 could significantly induce lysosomal biogenesis. In addition, compounds 1 and 3 could promote the nuclear translocation of TFEB, a master transcriptional factor of lysosomal genes, indicating that compounds 1 and 3 induced lysosomal biogenesis through activation of TFEB.