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

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 antiinflammation 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.

Peptides from Marine-Derived Fungi: Chemistry and Biological Activities

“…Since 239 displayed the same coupling constant of α-H with β-H (J α,β = 4.1 Hz) for the O,β-diMeTyr residue, as observed in 238, it, thus, supports the same relative configurations of C α and C β . The absolute configurations of C α and C β in 239 were suggested to be the same as those of C α and C β in 238 based on the NMR data and biosynthetic origin [116].…”

“…Compound 243 also showed the dose-dependent inhibition of NO production. Moreover, 243 effectively reduced the expression of iNOS (the enzyme responsible for NO production) and NLRP3 (an inflammatory mediator), suggesting that 243 could be a promising compound for the development of an anti-inflammatory agent [116].…”

Isolation and Structure Elucidation of New Metabolites from the Mariana-Trench-Associated Fungus Aspergillus sp. SY2601

“…Since then, more and more novel bioactive natural products have been continuously isolated from marine-derived Aspergillus species, including p -terphenyl derivatives of asperterphenyls A-N from A. sp. SCSIO41315 [ 6 ], cyclopentapeptides of pseudoviridinutans A-F from A. pseudoviridinutans TW58-5 [ 7 ], and indoloquinazoline alkaloids of clavutoines A-U from A. clavutus LZD32-24 [ 8 ].…”

Dipeniroqueforins A–B and Peniroqueforin D: Eremophilane-Type Sesquiterpenoid Derivatives with Cytotoxic Activity from Penicillium roqueforti

“…Natural products have fascinating chemical skeletons and potential bioactivities, which makes them play an indispensable role in many aspects of humanity. − Over the past few decades, traditional cultivation methods have become challenging to avoid repeated isolation of known compounds and discover structurally unique molecules with attractive bioactivities. − Recently, a Global Natural Products Social (GNPS) molecular networking strategy has been widely applied to solve the aforementioned problems. Molecular networking on the GNPS platform can help us to analyze the MS/MS fragment data and assess the structural similarities from the predicted metabolites, in which structurally similar compounds are clustered together in a visual network. − Consequently, the new structures of secondary metabolites can be precisely predicted from a crude extract before intensive chromatographic isolation, thereby speeding up their rapid discovery.…”