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

• Published in: Marine drugs 2023-10, Vol.21 (10), p.541
• Main Authors: Ning, Yaodong, Zhang, Shi, Zheng, Te, Xu, Yao, Li, Song, Zhang, Jianpeng, Jiao, Binghua, Zhang, Yun, Ma, Zengling, Lu, Xiaoling
• Format: Article
• Language: English
• Subjects: anti-inflammatory; Anti-inflammatory agents; Biological activity; Carbon; Cell culture; Cell migration; Culture media; diterpene; Diterpenes; Ethanol; Eutypella sp. D-1; Fermentation; Fungi; Inflammation; Metabolites; Migrations; Nitric oxide; Polar environments; Secondary metabolites; Spectrum analysis; Tetrahydrofuran; Zebrafish; zebrafish model
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md21100541

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.