Bisfischoids A and B, dimeric ent-abietane-type diterpenoids with anti-inflammatory potential from Euphorbia fischeriana Steud.

Two undescribed ent-abietane-type diterpenoid dimers with nonacyclic backbone formed by intermolecular [4 + 2] cycloaddition into a spirocyclic skeleton, bisfischoids A (1) and B (2), along with a known one fischdiabietane A (3), were identified from Euphorbia fischeriana Steud. Their structures were elucidated by extensive spectroscopic analysis, ECD and NMR calculation combined with DP4+ probability analysis, as well as X-ray diffraction. The anti-inflammatory potential of dimers 1-3 were examined using their inhibitory effects on soluble epoxide hydrolase (sEH), which revealed that 1 and 2 exhibited promising activities with inhibition constant (Ki) of 3.20 and 1.95 mu M, respectively. Further studies of molecular docking and molecular dynamics indicated that amino acid residue Tyr343 in the catalytic cavity of sEH was the key site for their inhibitory function.

Automated summary

Two undescribed ent-abietane-type diterpenoid dimers with nonacyclic backbone, bisfischoids A and B, were identified, along with a known compound fischdiabietane A, from Euphorbia fischeriana Steud. These compounds showed promising anti-inflammatory activities by inhibiting soluble epoxide hydrolase, with bisfischoid B exhibiting the strongest inhibitory effect. Further molecular docking studies revealed the key amino acid residue Tyr343 in the catalytic cavity of sEH for their inhibitory function.