Synthese von WNT aktiven Substanzen
One of the most important signaling pathways in different organisms is the Wnt/β-catenin pathway. A variety of biological processes like cell proliferation, cell differentiation and cell-cell communication are being controlled by the canonical Wnt/ β-catenin pathway.
On the basis of the lead structure of halochinon, which blocks the binding of β-catenin to its transcription factor TCF/LEF, a library of 9,10-phenanthrenchinones were synthesized. During biological studies the disulfoneamides of the phenanthrenchinone showed particularly high activities.
Other natural products like THC, indoles and cardenolides are also able to affect the Wnt/ β-catenin pathway. The compounds are not only tested in in vitro assays (luciferase) but also in vivo. The impact of calotropin on the morphogenesis of freshwater polyps (hydra) has been tested.
While our group focuses on the synthesis of the active compounds, the biological tests are performed in collaboration with the following groups:
Pui Lai Rachel Ee (Department of Pharmacy, National University of Singapore)
Dietmar Gradl (Institute of Zoology, KIT, Germany)
Thomas W. Holstein (Department of Molecular Evolution and Genomics, COS, University of Heidelberg)
Sonja Sievers/Herbert Waldmann (MPI Dortmund)