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

Glioma is a clinically heterogeneous type of brain tumor with a poor prognosis. Current treatment approaches have limited effectiveness in treating glioma, highlighting the need for novel drugs. One approach is to explore marine natural products for their therapeutic potential. In this study, we isolated nine shikimate-derived diisoprenyl-cyclohexene/ane-type meroterpenoids (1–9), including four new ones, amphicordins A–D (1–4) from the ascidian-derived fungus Amphichorda felina SYSU-MS7908, and further semisynthesized four derivatives (10–13). Their structures were extensively characterized using 1D and 2D NMR, modified Mosher’s method, HR-ESIMS, NMR and ECD calculations, and X-ray crystallography. Notably, amphicordin C (3) possesses a unique benzo[g]chromene (6/6/6) skeleton in this meroterpenoid family. In an anti-glioma assay, oxirapentyn A (7) effectively inhibited the proliferation, migration, and invasion of glioma cells and induced their apoptosis. Furthermore, an in silico analysis suggested that oxirapentyn A has the potential to penetrate the blood–brain barrier. These findings highlight the potential of oxirapentyn A as a candidate for the development of novel anti-glioma drugs

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

Glioma is a clinically heterogeneous type of brain tumor with a poor prognosis. Current treatment approaches have limited effectiveness in treating glioma, highlighting the need for novel drugs. One approach is to explore marine natural products for their therapeutic potential. In this study, we isolated nine shikimate-derived diisoprenyl-cyclohexene/ane-type meroterpenoids (1–9), including four new ones, amphicordins A–D (1–4) from the ascidian-derived fungus Amphichorda felina SYSU-MS7908, and further semisynthesized four derivatives (10–13). Their structures were extensively characterized using 1D and 2D NMR, modified Mosher’s method, HR-ESIMS, NMR and ECD calculations, and X-ray crystallography. Notably, amphicordin C (3) possesses a unique benzo[g]chromene (6/6/6) skeleton in this meroterpenoid family. In an anti-glioma assay, oxirapentyn A (7) effectively inhibited the proliferation, migration, and invasion of glioma cells and induced their apoptosis. Furthermore, an in silico analysis suggested that oxirapentyn A has the potential to penetrate the blood–brain barrier. These findings highlight the potential of oxirapentyn A as a candidate for the development of novel anti-glioma drugs

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

Glioma is a clinically heterogeneous type of brain tumor with a poor prognosis. Current treatment approaches have limited effectiveness in treating glioma, highlighting the need for novel drugs. One approach is to explore marine natural products for their therapeutic potential. In this study, we isolated nine shikimate-derived diisoprenyl-cyclohexene/ane-type meroterpenoids (1–9), including four new ones, amphicordins A–D (1–4) from the ascidian-derived fungus Amphichorda felina SYSU-MS7908, and further semisynthesized four derivatives (10–13). Their structures were extensively characterized using 1D and 2D NMR, modified Mosher’s method, HR-ESIMS, NMR and ECD calculations, and X-ray crystallography. Notably, amphicordin C (3) possesses a unique benzo[g]chromene (6/6/6) skeleton in this meroterpenoid family. In an anti-glioma assay, oxirapentyn A (7) effectively inhibited the proliferation, migration, and invasion of glioma cells and induced their apoptosis. Furthermore, an in silico analysis suggested that oxirapentyn A has the potential to penetrate the blood–brain barrier. These findings highlight the potential of oxirapentyn A as a candidate for the development of novel anti-glioma drugs

Integrating Genomics and Metabolomics for the Targeted Discovery of New Cyclopeptides with Antifungal Activity from a Marine-Derived Fungus Beauveria felina

Sour rot, caused by Geotrichum citri-aurantii, is a major postharvest disease in citrus and results in significant economic losses. The genus Beauveria is recognized as a promising source of biocontrol agents for agricultural applications. Herein, we established a targeted strategy by integrating genomics and metabolomics to accelerate the discovery of new cyclopeptides from antagonistic metabolites produced by the marine-derived fungus Beauveria felina SYSU-MS7908. As a result, we isolated and characterized seven cyclopeptides, including six new molecules, isaridins I-N (1–6). Their chemical structures and conformational analysis were extensively elucidated using spectroscopic techniques (NMR, HRMS, and MS’MS data), modified Mosher’s and Marfey’s methods, and single-crystal X-ray diffraction. Notably, isaridin K (3) contains a peptide backbone with an N-methyl-2-aminobutyric acid residue rarely found in natural cyclopeptides. Bioassays showed that compound 2 could significantly inhibit the mycelial growth of G. citri-aurantii by destroying the cell membrane. These findings provide an effective strategy for searching for new fungal peptides for potential agrochemical fungicides and also pave the way for further exploration of applications in agriculture, food, and medicine