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Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

Authors: Noorsaadah Abd Rahman; Stephen W. Doughty; Chin Fei Chee; Sek Peng Chin; Meyyammai Swaminathan; Lip Yong Chung; Michael J. C. Buckle;

Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

Abstract

Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM), comparable to that of acetylcholine (Ki = 59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

Keywords

Binding Sites, Receptor, Muscarinic M1, Alzheimer’s disease; muscarinic acetylcholine receptor; binding activity; flavonoids; molecular modelling, muscarinic acetylcholine receptor, Organic chemistry, Muscarinic Agonists, Flavones, Article, Protein Structure, Secondary, molecular modelling, Protein Structure, Tertiary, Rats, Molecular Docking Simulation, QD241-441, flavonoids, Animals, Alzheimer’s disease, binding activity, Protein Binding

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    20
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
20
Top 10%
Top 10%
Average
Green
gold