Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F14%3A10283022" target="_blank" >RIV/00179906:_____/14:10283022 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/14:43875136

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ijbiomac.2014.06.064" target="_blank" >http://dx.doi.org/10.1016/j.ijbiomac.2014.06.064</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijbiomac.2014.06.064" target="_blank" >10.1016/j.ijbiomac.2014.06.064</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers

Popis výsledku v původním jazyce

A new series of substituted tacrine/acridine and tacrine/tacrine dimers with aliphatic or alkylene-thiourea linkers was synthesized and the potential of these compounds as novel human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE) inhibitors with nanomolar inhibition activity was evaluated. The most potent AChE inhibitor was found to be homodimeric tacrine derivative 14a, which demonstrated an IC50 value of 2 nM; this value indicates an activity rate which is 250-times higher thanthat of tacrine 1 and 7500-times higher than 7-MEOTA 15, the compounds which were used as standards in the study. IC50 values of derivatives 1, 9, 10, 14b and 15 were compared with the dissociation constants of the enzyme-inhibitor complex, K-i1, and theenzyme-substrate-inhibitor complex, K-i2, for. A dual binding site is presumed for the synthesized compounds which possess two tacrines or tacrine and acridine as terminal moieties show evidence of dual site binding. DFT calculations of

Název v anglickém jazyce

Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers

Popis výsledku anglicky

A new series of substituted tacrine/acridine and tacrine/tacrine dimers with aliphatic or alkylene-thiourea linkers was synthesized and the potential of these compounds as novel human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE) inhibitors with nanomolar inhibition activity was evaluated. The most potent AChE inhibitor was found to be homodimeric tacrine derivative 14a, which demonstrated an IC50 value of 2 nM; this value indicates an activity rate which is 250-times higher thanthat of tacrine 1 and 7500-times higher than 7-MEOTA 15, the compounds which were used as standards in the study. IC50 values of derivatives 1, 9, 10, 14b and 15 were compared with the dissociation constants of the enzyme-inhibitor complex, K-i1, and theenzyme-substrate-inhibitor complex, K-i2, for. A dual binding site is presumed for the synthesized compounds which possess two tacrines or tacrine and acridine as terminal moieties show evidence of dual site binding. DFT calculations of

Druh

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

CEP obor

CE - Biochemie

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

International Journal of Biological Macromolecules

ISSN

0141-8130

e-ISSN

—

Svazek periodika

70

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

5

Strana od-do

435-439

Kód UT WoS článku

000342478800061

EID výsledku v databázi Scopus

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