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- W2280232103 abstract "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 β‐amyloid (Aβ)‐mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Aβ 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." @default.
- W2280232103 created "2016-06-24" @default.
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- W2280232103 date "2016-02-16" @default.
- W2280232103 modified "2023-09-28" @default.
- W2280232103 title "Novel 8-Hydroxyquinoline Derivatives as Multitarget Compounds for the Treatment of Alzheimer′s Disease" @default.
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- W2280232103 doi "https://doi.org/10.1002/cmdc.201600014" @default.
- W2280232103 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26880501" @default.
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