Molecular Networking-Guided Isolation of Cyclopentapeptides from the Hydrothermal Vent Sediment Derived Fungus Aspergillus pseudoviridinutans TW58-5 and Their Anti-inflammatory Effects.

Repetitive isolation of known compounds remains a major challenge in natural-product-based drug discovery. LC-MS/MS-based molecular networking has become a highly efficient strategy for the discovery of new natural products from complex mixtures. Herein, we report a molecular networking-guided isolation procedure, which resulted in the discovery of seven new cyclopentapeptides, namely, pseudoviridinutans A-F ( 1 - 7 ), from the marine-derived fungus Aspergillus pseudoviridinutans TW58-5. Compounds 1 - 7 feature a rare amino acid moiety, O ,β-dimethyltyrosine, observed for the first time from a marine-derived fungus. The planar structures of 1 - 7 were elucidated by detailed analyses of IR, UV, HR ESI-Q-TOF MS, and 1D and 2D NMR spectroscopic data. Meanwhile, their absolute configurations were determined through a combination of Marfey's method and X-ray diffraction. Subsequent bioassay revealed the anti-inflammation potential of 1 - 7 , especially 6 , which inhibited the production of nitric oxide (NO), a vital inflammatory mediator, in LPS-induced murine macrophage RAW264.7 cells by regulating the expression level of NLRP3 and iNOS.