Pimarane-Type Diterpenes with Anti-Inflammatory Activity from Arctic-Derived Fungus Eutypella sp. D-1.

The Arctic-derived fungus Eutypella sp. D-1 can produce numerous secondary metabolites, and some compounds exhibit excellent biological activity. Seven pimarane-type diterpenes, including three new compounds eutypellenone F ( 1 ), libertellenone Y ( 2 ), and libertellenone Z ( 3 ), and four known compounds ( 4 - 7 ), were isolated from fermentation broth of Eutypella sp. D-1 by the OSMAC strategy of adding ethanol as a promoter in the culture medium. Compound 2 has a rare tetrahydrofuran-fused pimarane diterpene skeleton. The anti-inflammatory activity of all compounds was evaluated. Compounds 3 - 6 showed a significant inhibitory effect on cell NO release at 10 μmol/L by in vitro experiments, of which 3 - 5 had inhibitory rates over 60% on nitric oxide (NO) release. Subsequently, the anti-inflammatory activity of 3 - 5 was evaluated based on a zebrafish model, and the results showed that 3 had a significant inhibitory effect on inflammatory cells migration at 40 μmol/L, while 4 and 5 had a significant inhibitory effect at 20 μmol/L. Moreover, compounds 3 - 5 have the same conjugated double bond structure, which may be an important group for these compounds to exert anti-inflammatory activity.