TacrineMINUS SIGN trolox hybrids: a novel class of centrally active, nonhepatotoxic multi-target-directed ligands exerting anticholinesterase and antioxidant activities with low in vivo toxicity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F15%3A43914847" target="_blank" >RIV/00023752:_____/15:43914847 - isvavai.cz</a>
Result on the web
<a href="http://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01325" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01325</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.5b01325" target="_blank" >10.1021/acs.jmedchem.5b01325</a>

Result language
angličtina
Original language name
TacrineMINUS SIGN trolox hybrids: a novel class of centrally active, nonhepatotoxic multi-target-directed ligands exerting anticholinesterase and antioxidant activities with low in vivo toxicity
Original language description
Coupling of two distinct pharmacophores, tacrine and trolox, endowed with different biological properties, afforded 21 hybrid compounds as novel multifunctional candidates against Alzheimer's disease. Several of them showed improved inhibitory propertiestoward acetylcholinesterase (AChE) in relation to tacrine. These hybrids also scavenged free radicals. Molecular modeling studies in tandem with kinetic analysis exhibited that these hybrids target both catalytic active site as well as peripheral anionic site of AChE. In addition, incorporation of the moiety bearing antioxidant abilities displayed negligible toxicity on human hepatic cells. This striking effect was explained by formation of nontoxic metabolites after 1 h incubation in human liver microsomes system. Finally, tacrineMINUS SIGN trolox hybrids exhibited low in vivo toxicity after im administration in rats and potential to penetrate across bloodMINUS SIGN brain barrier. All of these outstanding in vitro results in combinati
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Project
<a href="/en/project/ED2.1.00%2F03.0078" target="_blank" >ED2.1.00/03.0078: National institute of Mental Health</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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