化学
变构调节
烟碱激动剂
乙酰胆碱受体
受体
变构调节剂
乙酰胆碱
立体化学
药理学
生物物理学
生物化学
医学
生物
作者
Beatriz Balsera,José Mulet,Asia Fernández-Carvajal,Rafael Giménez Martínez,Antonio Ferrer-Montiel,José G. Hernández-Jiménez,Judith Estévez‐Herrera,Ricardo Borges,Andiara E. Freitas,Manuela G. López,M. Teresa García-López,Rosario González‐Muñiz,M. Jesús Pérez de Vega,Luis M. Valor,Lucie Svobodová,Salvador Sala,Francisco Sala,Manuel Criado
标识
DOI:10.1016/j.ejmech.2014.09.039
摘要
The α7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of α7 nicotinic function. The most potent compound (2,4,2′,5′-tetrahydroxychalcone, 111) was further characterized showing its potential as neuroprotective, analgesic and cognitive enhancer, opening the way for future developments around the chalcone structure.
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