Prati_2016_ChemMedChem_11_1284

Reference

Title : Novel 8-Hydroxyquinoline Derivatives as Multitarget Compounds for the Treatment of Alzheimer's Disease - Prati_2016_ChemMedChem_11_1284
Author(s) : Prati F , Bergamini C , Fato R , Soukup O , Korabecny J , Andrisano V , Bartolini M , Bolognesi ML
Ref : ChemMedChem , 11 :1284 , 2016
Abstract : We discovered a small series of hit compounds that show multitargeting activities against key targets in Alzheimer's disease (AD). The compounds were designed by combining the structural features of the anti-AD drug donepezil with clioquinol, which is able to chelate redox-active metals, thus decreasing metal-driven oxidative phenomena and beta-amyloid (Abeta)-mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Abeta self-aggregation. In addition, compounds 5-chloro-7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (1 b), 7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (2 b), and 7-(((1-benzylpiperidin-4-yl)amino)methyl)-5-chloro-8-hydroxyquinoline (3 a) are able to chelate copper(II) and zinc(II) and exert antioxidant activity in vitro. Importantly, in the case of 2 b, the multitarget profile is accompanied by high predicted blood-brain barrier permeability, low cytotoxicity in T67 cells, and acceptable toxicity in HUVEC primary cells.
ESTHER : Prati_2016_ChemMedChem_11_1284
PubMedSearch : Prati_2016_ChemMedChem_11_1284
PubMedID: 26880501

Related information

Citations formats

Prati F, Bergamini C, Fato R, Soukup O, Korabecny J, Andrisano V, Bartolini M, Bolognesi ML (2016)
Novel 8-Hydroxyquinoline Derivatives as Multitarget Compounds for the Treatment of Alzheimer's Disease
ChemMedChem 11 :1284

Prati F, Bergamini C, Fato R, Soukup O, Korabecny J, Andrisano V, Bartolini M, Bolognesi ML (2016)
ChemMedChem 11 :1284