1. Natural Polyhydroxy Flavonoids, Curcuminoids, and Synthetic Curcumin Analogs as α7 nAChRs Positive Allosteric Modulators
- Author
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Manuel Criado, Francisco Sala, Rosario González-Muñiz, Salvador Sala, María Jesús Pérez de Vega, José Mulet, Marta Ximenis, Ministerio de Ciencia, Innovación y Universidades (España), Consejo Superior de Investigaciones Científicas (España), and European Commission
- Subjects
Curcumin ,alpha7 Nicotinic Acetylcholine Receptor ,Phloretin ,curcuminoids ,Allosteric regulation ,Pharmacology ,Positive allosteric modulation ,Catalysis ,Article ,Inorganic Chemistry ,lcsh:Chemistry ,chemistry.chemical_compound ,Xenopus laevis ,α7 nicotinic acetylcholine receptor ,Allosteric Regulation ,Curcuminoids ,Diarylheptanoids ,mental disorders ,Animals ,Physical and Theoretical Chemistry ,Receptor ,Tetrahydrocurcuminoids ,Molecular Biology ,Evoked Potentials ,α7 nicotinic receptors ,lcsh:QH301-705.5 ,Spectroscopy ,Ion channel ,Biological evaluation ,Flavonoids ,Biological Products ,Dose-Response Relationship, Drug ,Organic Chemistry ,General Medicine ,Computer Science Applications ,Electrophysiological Phenomena ,chemistry ,tetrahydrocurcuminoids ,positive allosteric modulation ,lcsh:Biology (General) ,lcsh:QD1-999 ,Female ,α7 nachr - Abstract
The &alpha, 7 nicotinic acetylcholine receptor (&alpha, 7 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 &alpha, 7 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 &alpha, 7 nAChR. Biological evaluation showed that phloretin, demethoxycurcumin, and bis-demethoxicurcuming behave as PAMs of &alpha, 7 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.
- Published
- 2021