Viayna_2010_ChemMedChem_5_1855

Reference

Title : Novel huprine derivatives with inhibitory activity toward beta-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates - Viayna_2010_ChemMedChem_5_1855
Author(s) : Viayna E , Gomez T , Galdeano C , Ramirez L , Ratia M , Badia A , Clos MV , Verdaguer E , Junyent F , Camins A , Pallas M , Bartolini M , Mancini F , Andrisano V , Arce MP , Rodriguez-Franco MI , Bidon-Chanal A , Luque FJ , Camps P , Munoz-Torrero D
Ref : ChemMedChem , 5 :1855 , 2010
Abstract :

A new family of dual binding site acetylcholinesterase (AChE) inhibitors has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced beta-amyloid (Abeta) aggregation and beta-secretase (BACE-1), and to cross the blood-brain barrier. The new heterodimers consist of a unit of racemic or enantiopure huprine Y or X and a donepezil-related 5,6-dimethoxy-2-[(4-piperidinyl)methyl]indane moiety as the active site and peripheral site to mid-gorge-interacting moieties, respectively, connected through a short oligomethylene linker. Molecular dynamics simulations and kinetics studies support the dual site binding to AChE. The new heterodimers are potent inhibitors of human AChE and moderately potent inhibitors of human BChE, AChE-induced and self-induced Abeta aggregation, and BACE-1, and are predicted to be able to enter the central nervous system (CNS), thus constituting promising multitarget anti-Alzheimer drug candidates with the potential to modify the natural course of this disease.

PubMedSearch : Viayna_2010_ChemMedChem_5_1855
PubMedID: 20859987

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Citations formats

Viayna E, Gomez T, Galdeano C, Ramirez L, Ratia M, Badia A, Clos MV, Verdaguer E, Junyent F, Camins A, Pallas M, Bartolini M, Mancini F, Andrisano V, Arce MP, Rodriguez-Franco MI, Bidon-Chanal A, Luque FJ, Camps P, Munoz-Torrero D (2010)
Novel huprine derivatives with inhibitory activity toward beta-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates
ChemMedChem 5 :1855

Viayna E, Gomez T, Galdeano C, Ramirez L, Ratia M, Badia A, Clos MV, Verdaguer E, Junyent F, Camins A, Pallas M, Bartolini M, Mancini F, Andrisano V, Arce MP, Rodriguez-Franco MI, Bidon-Chanal A, Luque FJ, Camps P, Munoz-Torrero D (2010)
ChemMedChem 5 :1855