Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage - Preparation, in vitro screening and molecular docking

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F11%3A10100527" target="_blank" >RIV/00216208:11160/11:10100527 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/11:00002446 RIV/44555601:13440/11:43882723

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0968089610011120" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0968089610011120</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2010.12.021" target="_blank" >10.1016/j.bmc.2010.12.021</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage - Preparation, in vitro screening and molecular docking

Popis výsledku v původním jazyce

In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFPand then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of pi-pi or cation -pi interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed.

Název v anglickém jazyce

Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage - Preparation, in vitro screening and molecular docking

Popis výsledku anglicky

In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFPand then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of pi-pi or cation -pi interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed.

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/ME09086" target="_blank" >ME09086: Vývoj nových antidotních prostředků proti organofosforovým pesticidům</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

ISSN

0968-0896

e-ISSN

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Svazek periodika

19

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

754-762

Kód UT WoS článku

000287590500005

EID výsledku v databázi Scopus

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