Eur J Pharm Sci. 2012 Jan 23;45(1-2):169-83. doi: 10.1016/j.ejps.2011.11.004. Epub 2011 Nov 16.

Identification and characterization of diarylimidazoles as hybrid inhibitors of butyrylcholinesterase and amyloid beta fibril formation.

Karlsson D, Fallarero A, Brunhofer G, Guzik P, Prinz M, Holzgrabe U, Erker T, Vuorela P.

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Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, BioCity, Artillerigatan 6A, FI-20520 Turku, Finland.

Abstract

In this contribution, a chemical collection of aromatic compounds was screened for inhibition on butyrylcholinesterase (BChE)'s hydrolase activity using Ellman's reaction. A set of diarylimidazoles was identified as highly selective inhibitors of BChE hydrolase activity and amyloid β (Aβ) fibril formation. New derivatives were synthesized resulting in several additional hits, from which the most active was 6c, 4-(3-ethylthiophenyl)-2-(3-thienyl)-1H-imidazole, an uncompetitive inhibitor of BChE hydrolase activity (IC₅₀ BChE=0.10 μM; K(i)=0.073 ± 0.011 μM) acting also on Aβ fibril formation (IC₅₀=5.8 μM). With the aid of structure-activity relationship (SAR) studies, chemical motifs influencing the BChE inhibitory activity of these imidazoles were proposed. These bifunctional inhibitors represent good tools in basic studies of BChE and/or promising lead molecules for AD therapy.

PMID:: 22108346; [PubMed - indexed for MEDLINE]

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Identification and characterization of diarylimidazoles as hybrid inhibitors of butyrylcholinesterase and amyloid beta fibril formation.
Eur J Pharm Sci. 2012 Jan 23 ;45(1-2):169-83. doi: 10.1016/j.ejps.2011.11.004. Epub 2011 Nov 16 .

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