Instituto de Química Médica-Consejo Superior de Investigaciones Científicas (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, 03050 Sant Joan d'Alacant, Spain.
Int J Mol Sci. 2021 Jan 19;22(2):973. doi: 10.3390/ijms22020973.
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 were especially promising.
α7 烟碱型乙酰胆碱受体（α7 nAChR）是一种配体门控离子通道，与认知障碍、精神分裂症、疼痛和炎症有关。与完全激动剂相比，该受体的变构调节可能具有降低毒性的优势。我们之前用一些查尔酮获得的结果表明，它们是 α7 nAChR 的正变构调节剂（PAMs），这促使我们评估一些结构相关的天然黄酮类化合物和姜黄素类化合物以及一些合成姜黄素类似物的潜力，以鉴定 α7 nAChR 的新变构调节剂。生物评价表明，根皮素、去甲氧基姜黄素和双去甲氧基姜黄素是 α7 nAChR 的 PAMs。此外，一些新的姜黄素衍生物能够增强 ACh 引发的信号；四氢姜黄素类似物的活性值特别有希望。
