Discovery of New Highly Potent Histamine H3 Receptor Antagonists, Calcium Channel Blockers, and Acetylcholinesterase Inhibitors.
ACS Chem Neurosci
; 15(18): 3363-3383, 2024 Sep 18.
Article
en En
| MEDLINE
| ID: mdl-39208251
ABSTRACT
At present, one of the most promising strategies to tackle the complex challenges posed by Alzheimer's disease (AD) involves the development of novel multitarget-directed ligands (MTDLs). To this end, we designed and synthesized nine new MTDLs using a straightforward and cost-efficient one-pot Biginelli three-component reaction. Among these newly developed compounds, one particular small molecule, named 3e has emerged as a promising MTDL. This compound effectively targets critical biological factors associated with AD, including the simultaneous inhibition of cholinesterases (ChEs), selective antagonism of H3 receptors, and blocking voltage-gated calcium channels. Additionally, compound 3e exhibited remarkable neuroprotective activity against H2O2 and Aß1-40, and effectively restored cognitive function in AD mice treated with scopolamine in the novel object recognition task, confirming that this compound could provide a novel and innovative therapeutic approach for the effective treatment of AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bloqueadores de los Canales de Calcio
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Inhibidores de la Colinesterasa
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Antagonistas de los Receptores Histamínicos H3
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Enfermedad de Alzheimer
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia