Discovery of antioxidants and α-glycosidase inhibitors from an endophytic fungus Penicillium brefeldianum F4a

Oxidative stress significantly contributes to the progression of diabetes. The use of antioxidants or α-glycosidase inhibitors would be an effective therapeutic strategy for diabetes. To discover natural antioxidants or α-glycosidase inhibitors, two new compounds, penidione A (1) and peniorcinol D (2), were obtained from the endophytic fungus Penicillium brefeldianum F4a isolated from the roots of Houttuynia cordata Thunb. (Saururaceae). The structures were identified through a comprehensive analysis of spectroscopic data, including HR-ESI-MS, UV, IR, 1D and 2D NMR, together with quantum chemical calculations. Biological tests indicated that penidione A displayed weaker α-glycosidase inhibition activity than that of acarbose and peniorcinol D showed significant ABTS^•+ scavenging activity, comparable to that of l-ascorbic acid. Moreover, molecular docking analyses showed that penidione A had a good binding affinity with α-glycosidase, and the binding mode included hydrogen bonding and hydrophobic interaction. This work could provide valuable information for developing antioxidants or α-glycosidase inhibitors as lead compounds to treat diabetes.