Bioactive Polyhydroxanthones from Penicillium purpurogenum

Eight new polyhydroxanthones, penicixanthones A–H (1–8), including four monomers (1–4) and four dimers (5–8), were isolated from solid cultures of Penicillium purpurogenum SC0070. Their structures were elucidated by extensive spectroscopic analysis, X-ray single-crystal diffraction, and theoretical computations of ECD spectra. Penicixanthone B (2) has a hexahydroxanthone structure featuring an unusual oxygen bridge between C-6 and C-8a. Penicixanthone D (4) is distinct from other penicixanthones in stereochemistry, and its biosynthetic mechanism was proposed based on theoretical simulations for the reaction pathway of C-10a epimerization. Penicixanthone G (6) exhibited the most potent cytotoxicity (IC50: 0.3–0.6 μM) when tested against human carcinoma A549, HeLa, and HepG2 cells, whereas it was nontoxic to the normal Vero cells (IC50 > 50 μM). It also displayed the strongest antibacterial activity (MIC: 0.4 μg/mL) against both Staphylococcus aureus and the methicillin-resistant strain MRSA.