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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/GAP303%2F11%2F1907" target="_blank" >GAP303/11/1907: Nové inhibitory acetylcholinesterasy odvozené od látky 7-MEOTA - potenciální léčiva pro Alzheimerovu nemoc</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

—

Svazek periodika

55

Číslo periodika v rámci svazku

september

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

9

Strana od-do

23-31

Kód UT WoS článku

000309494100003

EID výsledku v databázi Scopus

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