The Chemotype of Chromanones as a Privileged Scaffold for Multineurotarget Anti-Alzheimer Agents

The multifactorial nature of Alzheimer's disease necessitates the development of agents able to interfere with different relevant targets. A series of 22 tailored chromanones was conceptualized, synthesized, and subjected to biological evaluation. We identified one representative bearing a link...

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Detalles Bibliográficos
Autores: Keuler, Tim, Lemke, Carina, Elsinghorst, Paul W., Iriepa Canalda, Isabel|||0000-0003-3475-9624, Chioua, Mourad, Martínez Grau, María Ángeles, Beadle, Christopher D., Vetman, Tatiana, López Muñoz, Francisco, Wille, Timo, Deuther Conrad, Winnie, Marco Contelles, José Luis, Gütschow, Michael
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/66689
Acceso en línea:http://hdl.handle.net/10017/66689
https://dx.doi.org/10.1021/acsptsci.2c00097
Access Level:acceso abierto
Palabra clave:Chromanones
Alzheimer's disease
Multineurotarget agents
σ1 and σ2 receptor
Human cholinesterases
Monoamine oxidases
Descripción
Sumario:The multifactorial nature of Alzheimer's disease necessitates the development of agents able to interfere with different relevant targets. A series of 22 tailored chromanones was conceptualized, synthesized, and subjected to biological evaluation. We identified one representative bearing a linker-connected azepane moiety (compound 19) with balanced pharmacological properties. Compound 19 exhibited inhibitory activities against human acetyl-, butyrylcholinesterase and monoamine oxidase-B, as well as high affinity to both the sigma 1 and sigma 2 receptors. Our study provides a framework for the development of further chromanone-based