(±)-: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channel Antagonism and Antiaggregating Properties for Alzheimer's Disease.
Fiche publication
Date publication
avril 2021
Journal
ACS chemical neuroscience
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGUET Aurélie, Pr HAFFEN Emmanuel
Tous les auteurs :
Ismaili L, Monnin J, Etievant A, Arribas RL, Viejo L, Refouvelet B, Soukup O, Janockova J, Hepnarova V, Korabecny J, Kucera T, Jun D, Andrys R, Musilek K, Baguet A, García-Frutos EM, De Simone A, Andrisano V, Bartolini M, de Los Ríos C, Marco-Contelles J, Haffen E
Lien Pubmed
Résumé
Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±) was identified as a promising new hit compound showing balanced activities toward the aforementioned recognized AD targets. Additional studies demonstrated antioxidant effects and brain penetration, along with the ability to inhibit the aggregation of both τ protein and β-amyloid peptide. The studies have shown that (±) (10 mg/kg intraperitoneally) significantly reduces scopolamine-induced cognitive deficits.
Mots clés
Alzheimer’s disease, Biginelli reaction, GSK 3β, MAO, calcium channel, cholinesterases
Référence
ACS Chem Neurosci. 2021 Apr 2;: