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, Isabel, Chioua, Mourad, Martínez-Grau, M. Angeles, Beadle, Christopher D., Vetman, T., López-Muñoz, Francisco, Wille, Timo, Bartz, Ulrike, Deuther-Conrad, W., Marco-Contelles, José, Gütschow, Michael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/295421
Acceso en línea:http://hdl.handle.net/10261/295421
Access Level:acceso abierto
Palabra clave:chromanones, Alzheimer’s disease, multineurotarget agents, σ1 and σ2 receptors, monoamine oxidases, human cholinesterases
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 σand σreceptors. Our study provides a framework for the development of further chromanone-based multineurotarget agents.