Identification and characterization of diarylimidazoles as hybrid inhibitors of butyrylcholinesterase and amyloid beta fibril formation
| Autor: | Michaela Prinz, Thomas Erker, Gerda Brunhofer, Przemyslaw Guzik, Adyary Fallarero, Daniela Karlsson, Pia Vuorela, Ulrike Holzgrabe |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Amyloid
Magnetic Resonance Spectroscopy Amyloid beta Stereochemistry DTNB Cell Survival Drug Evaluation Preclinical Pharmaceutical Science Thiophenes Mass Spectrometry Cell Line Small Molecule Libraries chemistry.chemical_compound Structure-Activity Relationship Alzheimer Disease Animals Humans Horses Molecular Targeted Therapy IC50 Butyrylcholinesterase Cholinesterase Amyloid beta-Peptides biology Imidazoles Acetylcholinesterase In vitro Recombinant Proteins Kinetics chemistry Biochemistry Electrophorus biology.protein Cholinesterase Inhibitors Uncompetitive inhibitor |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 45(1-2) |
| ISSN: | 1879-0720 |
| Popis: | 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; Ki = 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. |
| Databáze: | OpenAIRE |
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