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Structure-based development of nitroxoline derivatives as potential multifunctional anti-Alzheimer agentsKnez, Damijan, farmacevt ...Tremendous efforts have been dedicated to the development of effective therapeutics against Alzheimerʼs disease, which represents the most common debilitating neurodegenerative disease. ... Multifunctional agents are molecules designed to have simultaneous effects on different pathological processes. Such compounds represent an emerging strategy for the development of effective treatments against Alzheimerʼs disease. Here, we report on the synthesis and biological evaluation of a series of nitroxoline-based analogs that were designed by merging the scaffold of 8-hydroxyquinoline with that of a known selective butyrylcholinesterase inhibitor that has promising anti-Alzheimer properties. Most strikingly, compound 8g inhibits self-induced aggregation of the amyloid beta peptide (AŽ1-42), inhibits with sub-micromolarpotency butyrylcholinesterase (IC50 = 215 nM), and also selectively complexes Cu2+. Our study thus designates this compound as a promising multifunctional agent for therapeutic treatment of Alzheimerʼs disease. The crystal structure of human butyrylcholinesterase in complex with compound 8g is also solved, which suggests ways to further optimize compounds featuring the 8-hydroxyquinoline scaffold.Source: Bioorganic & Medicinal Chemistry. - ISSN 0968-0896 (Vol. 23, iss. 15, Aug. 2015, str. 4442-4452)Type of material - article, component part ; adult, seriousPublish date - 2015Language - englishCOBISS.SI-ID - 3874161
Author
Knez, Damijan, farmacevt |
Brus, Boris |
Coquelle, Nicolas |
Sosič, Izidor |
Šink, Roman |
Brazzolotto, Xavier |
Mravljak, Janez, 1978- |
Colletier, Jacques-Philippe |
Gobec, Stanislav, 1970-
Topics
Alzheimerjeva bolezen |
butirilholinesteraza |
večnamenski ligandi |
kelatiranje |
nitroksolin
source: Bioorganic & Medicinal Chemistry. - ISSN 0968-0896 (Vol. 23, iss. 15, Aug. 2015, str. 4442-4452)
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Knez, Damijan, farmacevt | 36438 |
Brus, Boris | 34508 |
Coquelle, Nicolas | |
Sosič, Izidor | 30816 |
Šink, Roman | 28862 |
Brazzolotto, Xavier | |
Mravljak, Janez, 1978- | 23419 |
Colletier, Jacques-Philippe | |
Gobec, Stanislav, 1970- | 15284 |
Source: Personal bibliographies
and: SICRIS
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