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Synthesis, molecular modelling and biological evaluation of novel heterodimeric, multiple ligands targeting cholinesterases and amyloid betaHebda, Michalina ...Cholinesterases and amyloid beta are one of the major biological targets in the search for a new and efficacious treatment of Alzheimer's disease. The study describes synthesis and pharmacological ... evaluation of new compounds designed as dual binding site acetylcholinesterase inhibitors. Among the synthesized compounds, two deserve special attention compounds 42 and 13. The former is a saccharin derivative and the most potent and selective acetylcholinesterase inhibitor (EeAChE IC50 = 70 nM). Isoindoline-1,3-dione derivative 13 displays balanced inhibitory potency against acetyl- and butyrylcholinesterase (BuChE) (EeAChE IC50 = 0.76 microM, EqBuChE IC50 = 0.618 microM), and it inhibits amyloid beta aggregation (35.8% at 10 microM). Kinetic studies show that the developed compounds act as mixed or non-competitive acetylcholinesterase inhibitors. According to molecular modelling studies, they are able to interact with both catalytic and peripheral active sites of the acetylcholinesterase. Their ability to cross the blood-brain barrier (BBB) was confirmed in vitro in the parallel artificial membrane permeability BBB assay. These compounds can be used as a solid starting point for further development of novel multifunctional ligands as potential anti-Alzheimer's agents.Source: Molecules [Elektronski vir]. - ISSN 1420-3049 (Vol. 21, iss. 4, 2016, str. 1-24)Type of material - article, component partPublish date - 2016Language - englishCOBISS.SI-ID - 4051313
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http://www.mdpi.com/1420-3049/21/4/410Odprti dostop
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DOI
Author
Hebda, Michalina |
Bajda, Marek |
Więckowska, Anna |
Szałaj, Natalia |
Pasieka, Anna |
Panek, Dawid |
Godyń, Justyna |
Wichur, Tomasz |
Knez, Damijan, farmacevt |
Gobec, Stanislav, 1970- |
Malawska, Barbara
Topics
Alzheimerjeva bolezen |
tarčna zdravila |
razvoj zdravil |
zaviralci acetilholinesteraze |
molekularno modeliranje
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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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Hebda, Michalina | |
Bajda, Marek | |
Więckowska, Anna | |
Szałaj, Natalia | |
Pasieka, Anna | |
Panek, Dawid | |
Godyń, Justyna | |
Wichur, Tomasz | |
Knez, Damijan, farmacevt | 36438 |
Gobec, Stanislav, 1970- | 15284 |
Malawska, Barbara |
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