Butenolide derivatives from the fungus Aspergillus terreus and their radical scavenging activity and protective activity against glutamate-induced excitotoxicity

The organic extract of cultured Aspergillus terreus displayed scavenging activity against ABTS(center dot+) and DPPH free radicals, and protective activity against glutamate-induced excitotoxicity in N18-RE-105 neuroblastoma-retina hybrid cells. Bioassay-guided fractionation of the active organic extract led to the isolation of total six butenolide derivatives, including one new metabolite, named butyroscavin (1), and five previously described metabolites, butyrolactones I (2), II (3), III (4), and VII (5), and aspernolide E (6). The planar structure of butyroscavin (1) was determined by the analysis of spectroscopic data including ESIMS (electrospray ionization mass spectrometry), and 1D and 2D NMR (nuclear magnetic resonance). The absolute configuration of butyroscavin (1) was assigned by comparison of the specific rotation with those of known compounds that share the same chiral carbon. All isolated compounds were active in the radical scavenging assay, whereas only butyrolactones I (2) and VII (5) exhibited protective activity against the glutamate-induced excitotoxicity with the EC50 of 130.1 and 91.9 mu M, respectively.