New Dibenzo-α-pyrone Derivatives with α-Glucosidase Inhibitory Activities from the Marine-Derived Fungus Alternaria alternata

Three new dibenzo-alpha-pyrone derivatives, alternolides A-C (1-3), and seven known congeners (4-10) were isolated from the marine-derived fungus of Alternaria alternata LW37 assisted by the one strain-many compounds (OSMAC) strategy. The structures of 1-3 were established by extensive spectroscopic analyses, and their absolute configurations were determined by modified Snatzke's method and electronic circular dichroism (ECD) calculations. Compounds 6 and 7 showed good 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant scavenging activities with IC50 values of 83.94 +/- 4.14 and 23.60 +/- 1.23 mu M, respectively. Additionally, 2, 3 and 7 exhibited inhibitory effects against alpha-glucosidase with IC50 values of 725.85 +/- 4.75, 451.25 +/- 6.95 and 6.27 +/- 0.68 mu M, respectively. The enzyme kinetics study indicated 2 and 3 were mixed-type inhibitors of alpha-glucosidase with K-i values of 347.0 and 108.5 mu M, respectively. Furthermore, the interactions of 2, 3 and 7 with alpha-glucosidase were investigated by molecular docking.