N-Methyl-N-((1-methyl-5-(3-(piperidin-1-yl)propoxy)-1H-benzo[d]imidazol-2-yl)methyl)prop-2-yn-1-amine (MBA-159), a new multitarget small molecule for the therapy of Alzheimer's disease

As part of a project aimed at the pharmacological optimization of Contilisant, herein we describe molecular modelling studies that led to the identification of MBA-159 as a new polyfunctionalized, multitarget-directed ligand and a promising drug candidate for the treatment of Alzheimer's diseas...

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Detalles Bibliográficos
Autores: Bautista-Aguilera, Óscar M., Manik, Aleksandra, Diez-Iriepa, Daniel, Szałaj, Natalia, Zaręba, Paula, Więckowska, Anna, Żmudzki, Paweł, Honkisz-Orzechowska, Ewelina, Knez, Damijan, Gobec, Stanislav, Sałat, Kinga, Martínez-Alonso, Borja, Guarnizo-Herrero, Víctor, Durán, Guillermo Torrado, Torrado-Salmerón, Carlos, Bellver-Sanchis, Aina, Nsiona-Defise, Inaya, Ribalta-Vilella, Marta, Pallàs, Mercè, López-Muñoz, Francisco, Griñán-Ferré, Christian, Marco-Contelles, José, Iriepa, Isabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/402078
Acceso en línea:http://hdl.handle.net/10261/402078
https://api.elsevier.com/content/abstract/scopus_id/105017041855
Access Level:acceso abierto
Palabra clave:ADME
Alzheimer’s disease
Biological evaluation
Molecular modelling
Descripción
Sumario:As part of a project aimed at the pharmacological optimization of Contilisant, herein we describe molecular modelling studies that led to the identification of MBA-159 as a new polyfunctionalized, multitarget-directed ligand and a promising drug candidate for the treatment of Alzheimer's disease. We synthesized MBA-159 and conducted comprehensive in vitro and in vivo evaluations. In in vivo studies MBA-159 demonstrated favourable pharmacokinetics, anti-amnesic properties and significantly improved non-spatial memory (contextual and recognition memory) in a mouse model of scopolamine-induced amnesia. Additionally, MBA-159 showed a tendency to increase synaptic plasticity biomarkers and reduce neuroinflammatory trends (assessed by qPCR), as well as cognitive enhancement in a senescence-accelerated prone mouse 8 model.

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