| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1371546 | Bioorganic & Medicinal Chemistry Letters | 2014 | 7 Pages |
Abstract
DYRK1A has been associated with Down’s syndrome and neurodegenerative diseases, therefore it is an important target for novel pharmacological interventions. We combined a ligand-based pharmacophore design with a structure-based protein/ligand docking using the software MOE in order to evaluate the underlying structure/activity relationship. Based on this knowledge we synthesized several novel β-carboline derivatives to validate the theoretical model. Furthermore we identified a modified lead structure as a potent DYRK1A inhibitor (IC50 = 130 nM) with significant selectivity against MAO-A, DYRK2, DYRK3, DYRK4 & CLK2.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Binia Drung, Christoph Scholz, Valéria A. Barbosa, Azadeh Nazari, Maria H. Sarragiotto, Boris Schmidt,