Anti-Inflammatory and Proangiogenic Metabolites from the Hadal Trench-Derived Fungus Acremonium dichromosporum YP-213

Author:

Zhang Yan1,Zhou Jia-Bao1,Yang Shu-Ting1,Liu Xin1,Cao Wei1,Li Pei-Hai2,Chen Hao3,Fan Ya-Qin13

Affiliation:

1. Shandong Provincial Key Laboratory of Applied Mycology, School of Life Sciences, Qingdao Agricultural University, Qingdao 266109, China

2. Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China

3. MNR Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China

Abstract

Four new compounds, including two ascochlorin-type meroterpenoids acremocholrins A (1) and B (2), one pyridone alkaloid acremopyridone A (7), and one cyclopentenone derivative acremoketene A (12), together with eight known compounds (3–6 and 8–11), were isolated and identified from the hadal trench-derived fungus Acremonium dichromosporum YP-213. Their structures were determined with a detailed spectroscopic analysis of NMR and MS data, NOE analysis, octant rule and quantum chemical calculations of ECD, and NMR (with DP4+ probability analysis). Among the compounds, 7 represent a novel scaffold derived from a pyridone alkaloid by cleavage of the C-16-C-17 bond following oxidation to give a ketone. Compounds 9, 11, and 12 showed potent in vivo anti-inflammatory activity in transgenic zebrafish, while compound 8 exhibited significant proangiogenic activity in transgenic zebrafish.

Funder

National Key R&D Program of China

National Natural Science Foundation of China

Shandong Provincial Natural Science Foundation

China Postdoctoral Science Foundation

Publisher

MDPI AG

Subject

Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science

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