Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578.

Seven new polyketides, diphenyl ketone (1), diphenyl ketone glycosides (2-4), diphenyl ketone-diphenyl ether dimer (6), and anthraquinone-diphenyl ketone dimers (7 and 8), together with compound 5, were isolated from the psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-3578 fermented at 16 °C and identified by spectroscopic analysis. The absolute configurations of 2-4 were determined by acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization. The configuration of 5 was first determined by X-ray diffraction analysis. Compounds 6 and 8 showed the highest activity against amyloid beta (Aβ42) aggregation with half-maximal inhibitory concentrations (IC50) of 0.10 and 0.18 μM, respectively. They also showed strong abilities to chelate with metal ions, especially iron, were sensitive to Aβ42 aggregation induced by metal ions, and displayed depolymerizing activity. Compounds 6 and 8 show potential as leads for the treatment of Alzheimer's disease to prevent Aβ42 aggregation.