A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1

Four quinolinones (1–4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium crustosum AP2T1. In addition, five new quinolinone derivatives (5–9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC50-24 h of 8.4 μg/mL and 30.7 μg/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.