Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors - implications for early Myasthenia gravis treatment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F11%3A10100523" target="_blank" >RIV/00216208:11160/11:10100523 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/11:00002426 RIV/44555601:13440/11:43881362

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0960894X11002319" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0960894X11002319</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmcl.2011.02.047" target="_blank" >10.1016/j.bmcl.2011.02.047</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors - implications for early Myasthenia gravis treatment

Popis výsledku v původním jazyce

This paper describes the preparation and in vitro evaluation of 18 newly prepared bis-quinolinium inhibitors on human recombinant acetylcholinesterase (AChE) and human plasmatic butyrylcholinesterase (BChE). Their inhibitory (IC(50)) and was compared tothe chosen standards ambenonium dichloride, edrophonium chloride, BW284c51 and ethopropazine hydrochloride. One novel compound was found to be a promising inhibitor of hAChE (in nM range) and was better than edrophonium chloride or BW284c51, but was worse than ambenonium chloride. This compound also showed selectivity towards hAChE and it was confirmed as a non-competitive inhibitor of hAChE by kinetic analysis. A molecular modelling study further confirmed its binding to the peripheral active site of hAChE via apparent pi-pi or pi-cationic interactions.

Název v anglickém jazyce

Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors - implications for early Myasthenia gravis treatment

Popis výsledku anglicky

This paper describes the preparation and in vitro evaluation of 18 newly prepared bis-quinolinium inhibitors on human recombinant acetylcholinesterase (AChE) and human plasmatic butyrylcholinesterase (BChE). Their inhibitory (IC(50)) and was compared tothe chosen standards ambenonium dichloride, edrophonium chloride, BW284c51 and ethopropazine hydrochloride. One novel compound was found to be a promising inhibitor of hAChE (in nM range) and was better than edrophonium chloride or BW284c51, but was worse than ambenonium chloride. This compound also showed selectivity towards hAChE and it was confirmed as a non-competitive inhibitor of hAChE by kinetic analysis. A molecular modelling study further confirmed its binding to the peripheral active site of hAChE via apparent pi-pi or pi-cationic interactions.

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/GP203%2F09%2FP130" target="_blank" >GP203/09/P130: Vývoj nových inhibitorů acetylcholinesterasy jako léčiv Myasthenia gravis</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

e-ISSN

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Svazek periodika

21

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

5

Strana od-do

2505-2509

Kód UT WoS článku

000289074700070

EID výsledku v databázi Scopus

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