Peniexpansones A–F: polyketides from Penicillium expansum DWS880 capable of enhancing the activity of fluconazole against Candida albicans

Six new polyketides, peniexpansones A-F (1-4, 6, 7), along with an additional novel compound, (2E,4E,6E)-8-methyldeca-2,4,6-trienoic acid (5), and a known naphthopyrone, were isolated from the ethyl acetate extract of rice fermented with the soil fungus Penicillium expansum DWS880. Structurally, peniexpansones A-D feature a highly oxygenated tetrahydronaphthalene moiety linked to an acyl chain. The structures of the new compounds were elucidated by extensive spectroscopic analysis (1D/2D NMR and HRESIMS) and further supported by quantum chemical calculations. Peniexpansone C showed weak cytotoxicity against HCT116 cells (IC₅₀ 22.81 ± 0.42 μM) and moderate antimicrobial activity against pathogens including Staphylococcus aureus and Candida albicans. Moreover, peniexpansones A and B, can significantly improve the anti-fungal activity of fluconazole against resistant Candida albicans. Our results provided new structures for the future development of efficiency enhancement agents for anti-fungal drugs.