Marine Fungi as Producers of Benzocoumarins, a New Class of Inhibitors of Glycogen-Synthase-Kinase 3β
Jutta Wiese,
Johannes F. Imhoff,
Tobias A. M. Gulder,
Antje Labes,
Rolf Schmaljohann
Affiliations
Jutta Wiese
GEOMAR Helmholtz Center for Ocean Research Kiel, Marine Microbiology, Düsternbrooker Weg 20, 24105 Kiel, Germany
Johannes F. Imhoff
GEOMAR Helmholtz Center for Ocean Research Kiel, Marine Microbiology, Düsternbrooker Weg 20, 24105 Kiel, Germany
Tobias A. M. Gulder
Biosystems Chemistry, Department of Chemistry and Center for Integrated Protein Science Munich (CISPM), Technical University of Munich, Lichtenbergstraße 4, 85748 Garching, Germany
Antje Labes
GEOMAR Helmholtz Center for Ocean Research Kiel, Marine Microbiology, Düsternbrooker Weg 20, 24105 Kiel, Germany
Rolf Schmaljohann
GEOMAR Helmholtz Center for Ocean Research Kiel, Marine Microbiology, Düsternbrooker Weg 20, 24105 Kiel, Germany
The glycogen-synthase-kinase 3 (GSK-3) is an important target in drug discovery. This enzyme is involved in the signaling pathways of type 2 diabetes, neurological disorders, cancer, and other diseases. Therefore, inhibitors of GSK-3 are promising drug candidates for the treatment of a broad range of diseases. Here we report pannorin (1), alternariol (2), and alternariol-9-methylether (3) to be promising inhibitors of the isoform GSK-3β showing sub-μM IC50 values. The in vitro inhibition is in the range of the known highly active GSK-3β inhibitor TDZD-8. Compounds 1–3 have a highly oxygenated benzocoumarin core structure in common, which suggests that this may be a new structural feature for efficient GSK-3β inhibition.
