Molecular networking-guided discovery of anti-inflammatory diterpenoids from the roots of Euphorbia prolifera
Xiuli Wang1, Yang Xu1, Yali Wang2
1Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Abstract:
Molecular-network-guided mining of a diterpenoid extract from Euphorbia prolifera Buch.-Ham. ex D.Don roots highlighted a cluster assigned to myrsinane-type diterpenoids. This directed the isolation of six undescribed myrsinanes, one tigliane-type diterpene and 27 known diterpenoids. Structures were established by 1D/2D NMR, HR-ESI-MS, ECD calculations, and X-ray crystallography. Notably, (2S,3S,4R,5R,6R,7R,9S,11S,12R,13S,14S,15R)-3β-O-propionyl-5α-O-benzoyl-7β-O-acetyl-17,14-oxo-premyrsinol (1) is the first myrsinane-type diterpene with 14/17-oxygen bridge. All compounds exhibited their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Compounds 18, 19, and 31 showed significant inhibitory effects, and the IC50 values of compound 19 reached 8.7 ± 1.31 μM.
