1. Acetylcholinesterase inhibitors from the toadstool Cortinarius infractus
- Author
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Wolfgang Brandt, Torsten Geissler, Astrid Kehlen, Norbert Arnold, Andrea Porzel, Dagmar Schlenzig, and Ludger A. Wessjohann
- Subjects
Erythrocytes ,Aché ,Cortinarius infractus ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,Heterocyclic Compounds, 4 or More Rings ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Pharmacokinetics ,Drug Discovery ,Animals ,Fruiting Bodies, Fungal ,Cytotoxicity ,Molecular Biology ,Butyrylcholinesterase ,Molecular Structure ,biology ,Organic Chemistry ,Stereoisomerism ,biology.organism_classification ,Acetylcholinesterase ,language.human_language ,Drug development ,chemistry ,Docking (molecular) ,language ,Molecular Medicine ,Cattle ,Cholinesterase Inhibitors ,Agaricales - Abstract
Inhibition of acetylcholinesterase (AChE) and therefore prevention of acetylcholine degradation is one of the most accepted therapy opportunities for Alzheimer´s disease (AD), today. Due to lack of selectivity of AChE inhibitor drugs on the market, AD-patients suffer from side effects like nausea or vomiting. In the present study the isolation of two alkaloids, infractopicrin (1) and 10-hydroxy-infractopicrin (2), from Cortinarius infractus Berk. (Cortinariaceae) is presented. Both compounds show AChE-inhibiting activity and possess a higher selectivity than galanthamine. Docking studies show that lacking π–π-interactions in butyrylcholinesterase (BChE) are responsible for selectivity. Studies on other AD pathology related targets show an inhibitory effect of both compounds on self-aggregation of Aβ-peptides but not on AChE induced Aβ-peptide aggregation. Low cytotoxicity as well as calculated pharmacokinetic data suggest that the natural products could be useful candidates for further drug development.
- Published
- 2010
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