Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F12%3A43874729" target="_blank" >RIV/60162694:G44__/12:43874729 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.ejmech.2012.06.051" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2012.06.051</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2012.06.051" target="_blank" >10.1016/j.ejmech.2012.06.051</a>

Result language
angličtina
Original language name
Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease
Original language description
New tacrine derivatives 5a-d, 6a-d with piperazino-ethyl spacer linked with corresponding secondary amines and tacrine homodimer 8 were synthesized and tested as cholinesterase inhibitors on human acetylcholinesterase (hAChE) and human plasmatic butyrylcholinesterase (hBChE). In most cases the majority of synthesized derivatives exhibit a high AChE and BChE inhibitory activity with IC50 values in the low-nanomolar range, being clearly more potent than the reference standard tacrine (9-amino-1,2,3,4-tetrahydroacridine, 1) and 7-MEOTA (7-methoxy-9-amino-1,2,3,4-tetrahydroacridine). Among them, inhibitors 8 and 5c, showed a strong inhibitory activity against hAChE, with an IC50 value of 4.49 nM and 4.97, nM resp., and a high selectivity to hAChE. The compound 5d acted as the most potent inhibitor against hBChE with an IC50 value of 33.7 nM and exhibited also a good selectivity towards hBChE. The dissociation constants K-i of the selected inhibitors were compared with their IC50 values. Mo
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/GAP303%2F11%2F1907" target="_blank" >GAP303/11/1907: Novel inhibitors of acetylcholinesterase derived from 7-MEOTA - potential Alzheimer´s disease drugs</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2012
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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