Five undescribed chromone-phenylpyridone hybrids from Cineraria repanda-derived Penicillium oxalicum with cytotoxic and antibacterial activity

Five previously undescribed phenylpyridones, designated as citridones H–L (1–5), along with seven known compounds, were characterized from the rice medium culture of the Cineraria repanda-derived endophytic fungus Penicillium oxalicum. Their structures were elucidated through detailed interpretation of UV, NMR, and HR-ESI-MS data. The absolute configurations of C-2 and C-3 in compounds 1–4 were determined by spectroscopic analysis and ECD calculations, while the C-5′ configurations were established through computational ¹³C NMR and DP4+ analyses. These compounds represent a novel scaffold of chromone-phenylpyridone hybrids, making only the second report of such compounds from the Penicillium genus and the first to feature a unique (E)-5-methylhepta-1,3-diene group at the C-2 position. Additionally, a biosynthetic pathway for these novel chromone-phenylpyridones is proposed for the first time. Notably, compounds 3 and 4 exhibited cytotoxicity against HCT116 and H1299 cell lines when used in combination, with IC₅₀ values of 4.15 ± 0.34 and 9.07 ± 1.64 μM, respectively. Furthermore, compounds 3, 4 and 5 demonstrated significant inhibitory effects against Staphylococcus aureus, with MIC values of 64, 64 and 8 μg/mL, respectively.