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

Abstract Six new polyketides, peniexpansones A–F ( 1 – 4 , 6 , 7 ), along with an additional novel compound, (2 E ,4 E ,6 E )-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 (IC 50 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. Graphical Abstract