Unprecedented diterpenoid dimers with soluble epoxide hydrolase inhibitory effect from

• Published in: Organic & biomolecular chemistry Vol. 2; no. 12; pp. 258 - 2517
• Main Authors: Zhao, Wen-Yu, Sun, Cheng-Peng, Chang, Yi-Bo, Wang, Wei-Yi, Yan, Jian-Kun, Lv, Xia, Wang, Chao, Ma, Xiao-Chi
• Format: Journal Article
• Published: 23.03.2022
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d2ob00053a

Biseuphoids A ( 1 ) and B ( 2 ), two unprecedented ent -abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12′ and C-17-C-11′, respectively, were isolated from Euphorbia fischeriana , along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B ( 3 ), caudicifolin ( 4 ), and fischeriabietane C ( 5 ). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions. The novel dimers 1 and 2 exhibited inhibitory activities on soluble epoxide hydrolase (sEH) with IC 50 values of 8.17 and 5.61 μM, respectively. Molecular dynamics studies illustrated that both 1 and 2 can occupy the catalytic pocket of sEH by forming stable hydrogen bonds with the key amino acid residues including Gln384, Asn378, Pro361, Ala365, Asn366, and Asn472. Two unprecedented diterpenoids possibly derived from Michael addition into dimeric skeletons linked by monomeric ent -abietanes through C-17-C-12′ or C-17-C-11′ were identified from the medicinal herb Euphorbia fischeriana .