Molecular Networking-Guided Isolation of Cyclopentapeptides from the Hydrothermal Vent Sediment Derived Fungus <i>Aspergillus pseudoviridinutans</i> TW58-5 and Their Anti-inflammatory Effects
Wenjuan Ding, Danmei Tian, Mei Chen, Zixuan Xia, Xiyang Tang, Sihao Zhang, Jihua Wei, Xunuo Li, Xin‐Sheng Yao, Bin Wu, Jinshan Tang
Abstract
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.