| Literature DB >> 17943713 |
Rajeshwar Narlawar1, Marcus Pickhardt, Stefanie Leuchtenberger, Karlheinz Baumann, Sabine Krause, Thomas Dyrks, Sascha Weggen, Eckhard Mandelkow, Boris Schmidt.
Abstract
Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar concentrations.Entities:
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Year: 2008 PMID： 17943713 DOI： 10.1002/cmdc.200700218
Source DB: PubMed Journal: ChemMedChem ISSN： 1860-7179 Impact factor: 3.466