Antiglioma Natural Products from the Marine-Associated Fungus Penicillium sp. ZZ1750

Abstract

Marine-derived Penicillium fungi are one of the most important sources for the discovery of new bioactive natural products. This study characterized the isolation, structures, and antiglioma activities of twelve compounds, including three novel ones— penipyridinone B (1), 11S-(–)-penilloid A (2), and 11R,14E-(+)-penilloid A (3)—from the marine fungus Penicillium sp. ZZ1750. The structures of the novel compounds were determined via extensive nuclear magnetic resonance (NMR) spectroscopic analyses, high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, Mosher¢s method, optical rotation (OR) calculations, and electronic circular dichroism (ECD) calculations. Penipyridinone B represents the first example of its structural type and showed potent antiglioma activity, with IC50 values of 2.45 mM for U87MG cells and 11.40 mM for U251 cells. The known compounds of questiomycin A (9) and xanthocillin X (10) also showed antiproliferative activity against both U87MG and U251 cells, with IC50 values of 13.65 mM to 22.56 mM. The antiglioma activity of questiomycin A and xanthocillin X may be related to the promotion of reactive oxygen species (ROS) production, the reduction of mitochondrial membrane potential (MMP), and the enhancement of caspase-3 enzyme activity.

Marine natural products

“…238 Coculture of two deep-sea-derived Penicillium strains resulted in isolation of sesquiterpenes 740 and 741 from one strain and organic acid 742 from the other 239 and other sediment-derived Penicillium strains were the source of meroterpenoid 743 (ref. 240) and alkaloids 744, 745, 240 746, 747. 241 Polyketide derivatives 748-752, were isolated from a Pestalotiopsis strain 242 and tyrosine derivative 753 and terezine derivatives 754 and 755 were obtained from Phoma herbarum.…”

Shikimate-Derived Meroterpenoids from the Ascidian-Derived Fungus Amphichorda felina SYSU-MS7908 and Their Anti-Glioma Activity

“…13−15 To date, researchers have identified 39 anti-glioma active molecules from four genera of marine fungi (Halorosellinia, Xylaria, Diaporthe, Penicillium, Trichobotrys). These metabolites exhibit diverse chemical structures, including polyketides (anthraquinone derivative SZ-685C, 16 xyloketal B, 17 six dimeric xanthones, 18 and calyxanthone 19 ), alkaloids (pyrrocidines, trichobamide A, 20 pyrrospirones C−J, 21,22 penicipyrrodiether A, 23 penicipyrroether A, 21 questiomycin A, 24 and xanthocillin X 24 ), terpenoids (the sesquiterpenoid purpuride G 25 triterpenoid penidifarnesylin A 26 ), glycosylated alkylresorcinols (peniresorcinosides A−E 26 ), and a meroterpenoid (penipyridinone B 24 ). In our search for bioactive secondary metabolites from ascidian-derived fungi in the South China Sea, 18,20,27−30 we discovered that a culture extract of the fungus Amphichorda felina SYSU-MS7908 exhibited moderate cytotoxicity against U87-MG human glioma cells.…”

“…In recent years, marine fungi have become a significant source of new marine natural products, accounting for more than 40% of discoveries from 2018 to 2021. − As a result, exploring marine fungi has become an effective strategy for discovering lead compounds with potential anti-glioma properties. − To date, researchers have identified 39 anti-glioma active molecules from four genera of marine fungi ( Halorosellinia , Xylaria , Diaporthe , Penicillium , Trichobotrys ). These metabolites exhibit diverse chemical structures, including polyketides (anthraquinone derivative SZ-685C, xyloketal B, six dimeric xanthones, and calyxanthone), alkaloids (pyrrocidines, trichobamide A, pyrrospirones C–J, , penicipyrrodiether A, penicipyrroether A, questiomycin A, and xanthocillin X), terpenoids (the sesquiterpenoid purpuride G and the triterpenoid penidifarnesylin A), glycosylated alkylresorcinols (peniresorcinosides A–E), and a meroterpenoid (penipyridinone B).…”