Identification and structural modification of ent-rosane diterpenoids from Euphorbia milii inhibiting RANKL-induced osteoclastogenesis.
Bioorg Chem
; 145: 107253, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38452588
ABSTRACT
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), underscoring the significance of acylated A-ring moieties in the ent-rosane skeleton for anti-osteoclastogenesis. Thirteen synthetic derivatives were obtained through esterification of 17. Of these, compound 27 exhibited remarkable improvement, with an IC50 of 0.8 µM, more than a 12-fold increase in potency compared to the parent compound 17 (IC50 > 10 µM). This work presents a series of new ent-rosane diterpenoids with potential antiosteoporosis agents.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Euphorbia
/
Diterpenos
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2024
Tipo de documento:
Article