Unprecedented diterpenoid dimers with soluble epoxide hydrolase inhibitory effect from Euphorbia fischeriana.
Org Biomol Chem
; 20(12): 2508-2517, 2022 03 23.
Article
em En
| MEDLINE
| ID: mdl-35266497
ABSTRACT
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 IC50 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Euphorbia
/
Diterpenos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article