Antifungal phenolic glucosides and related congeners from the cold-seep-derived Talaromyces trachyspermus CS-106

Chemical investigation of the cold-seep-sourced fungus Talaromyces trachyspermus CS-106 resulted in the isolation of six previously undescribed phenolic glucopyranosides, talarosides A-F (1-6), two previously undescribed phenolic cysteine derivatives, talacysteines A and B (7 and 8), and five known congeners 9-13. The results from in vitro bioassay indicated that compounds 3, 6, and 9 displayed potent activities against several tested phytopathogenic fungal strains. Specially, the chloroquinone derivative, 2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (compound 9), exhibited a broad spectrum of fungicidal activity against Alternaria brassicae, Colletotrichum gloeosporioides, Fusarium graminearum, and F. oxysporum, with MIC values ranging from 0.5 to 4 μg/mL. In vivo testing on tomato fruits showed that 9 displayed considerable curative efficacy against F. oxysporum. Both scanning electron microscopy and cryo-SEM analysis indicated that 9 possessed a strong ability to destroy the surface morphology of mycelia and seriously interfere with the growth of the fungal pathogen. Compound 9 also exhibited pronounced succinate dehydrogenase (SDH) inhibitory activity from the in vitro SDH inhibitory assay. Molecular docking simulations were performed to explore the intermolecular interaction of 9 with SDH enzyme from F. oxysporum. These findings presented a promising lead compound such as compound 9 for the discovery of SDH inhibitor as antifungal agents.