Natural Polyhydroxy Flavonoids, Curcuminoids, and Synthetic Curcumin Analogs as α7 nAChRs Positive Allosteric Modulators.

Autor: Ximenis M; Instituto de Química Médica-Consejo Superior de Investigaciones Científicas (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain., Mulet J; Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain., Sala S; Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain., Sala F; Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain., Criado M; Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain., González-Muñiz R; Instituto de Química Médica-Consejo Superior de Investigaciones Científicas (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain., Pérez de Vega MJ; Instituto de Química Médica-Consejo Superior de Investigaciones Científicas (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Jan 19; Vol. 22 (2). Date of Electronic Publication: 2021 Jan 19.
DOI: 10.3390/ijms22020973
Abstrakt: The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain, and inflammation. Allosteric modulation of this receptor might be advantageous to reduce the toxicity in comparison with full agonists. Our previous results obtained with some hydroxy-chalcones, which were identified as positive allosteric modulators (PAMs) of α7 nAChR, prompted us to evaluate the potential of some structurally related naturally occurring flavonoids and curcuminoids and some synthetic curcumin analogues, with the aim of identifying new allosteric modulators of the α7 nAChR. Biological evaluation showed that phloretin, demethoxycurcumin, and bis-demethoxicurcuming behave as PAMs of α7 nAChR. In addition, some new curcumin derivatives were able to enhance the signal evoked by ACh; the activity values found for the tetrahydrocurcuminoid analog 23 were especially promising.
Databáze: MEDLINE
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