Identification and structural modification of ent-rosane diterpenoids from Euphorbia milii inhibiting RANKL-induced osteoclastogenesis

• Published in: Bioorganic chemistry 2024-04, Vol.145, p.107253-107253, Article 107253
• Main Authors: Peng, Xing, Liu, Shaonan, Zhang, Yuting, Xu, Jun, Gu, Qiong
• Format: Article
• Language: English
• Subjects: Anti-osteoporosis; Ent-atisane diterpenoid; Ent-rosane diterpenoid; Euphorbia milii
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107253

[Display omitted] •Sixteen undescribed, structurally diverse and novel diterpenoids were characterized from Euphorbia milii.•Thirteen synthetic derivatives were prepared, and a 12-fold increase in inhibitory potency was gained through structural derivation.•Fifteen anti-osteoclastogenesis diterpenoids were identified. Phytochemical study on Euphorbia milii, a common ornamental plant, resulted in the identification of thirteen new ent-rosane diterpenoids (1–13), three new ent-atisane diterpenoids (14–16), and a known ent-rosane (17). Their structures were delineated using spectroscopic data, quantum chemical calculations, and X-ray diffraction experiments. Euphomilone F (1) represented a rare ent-rosane-type diterpenoid with a 5/7/6 skeleton. Euphoainoid G (8) was a rare rosane diterpenic acid. Compounds 9 and 10 carried infrequent tetrahydrofuran rings, and compounds 11–13 was 18-nor-ent-rosane diterpenoids. All isolates were evaluated for their inhibitory effects on RANKL-induced osteoclasts. Notably, compounds with aromatic ester groups (2–7) showed promising activities (IC50  10 μM). This work presents a series of new ent-rosane diterpenoids with potential antiosteoporosis agents.