Amyloid-β aggregation inhibitory activity and neuroprotective effects of metabolites of Trichoderma pluripenicillatum.

Three new compounds, pluripenicillatumols І-ІІІ (1-3), and five known compounds (4-8) were isolated from the fungus, Trichoderma pluripenicillatum JKYM-KI28. The planar chemical structures and relative configurations of 1 and 2 and the geometry of 3 were elucidated using high-resolution mass spectrometry, one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, and DP4+ analysis using the calculated 13C NMR chemical shifts. The absolute configurations of 1 and 2 were determined using electronic circular dichroism calculations. Further bioassays for the isolated compounds, 3-6, indicated inhibitory effects against amyloid-(Aβ) aggregation and neuroprotective effects against Aβ-induced cytotoxicity in human induced pluripotent stem cell-derived basal forebrain cholinergic neurons. These results suggest that the new compounds in this study may have potency as Alzheimer's disease treatments and as preventive agents via Aβ aggregation inhibition and neuroprotection.