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ChemMedChem. 2008 Jan;3(1):165-72.

Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease?

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1
Clemens Schöpf Institute of Chemistry and Biochemistry, Darmstadt University of Technology, Petersenstrasse 22, 64287 Darmstadt, Germany.

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.

PMID:
17943713
DOI:
10.1002/cmdc.200700218
[Indexed for MEDLINE]
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