In silico pharmacophore modeling on known pyridinium oxime reactivators of cyclosarin (GF) inhibited AChE to aid discovery of potential, more efficacious novel non-oxime reactivators

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F13%3A43874977" target="_blank" >RIV/60162694:G44__/13:43874977 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/13:50001352

Výsledek na webu

<a href="http://benthamscience.com/journal/contents.php?journalID=ccadd&issueID=114807" target="_blank" >http://benthamscience.com/journal/contents.php?journalID=ccadd&issueID=114807</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/15734099113099990012" target="_blank" >10.2174/15734099113099990012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

In silico pharmacophore modeling on known pyridinium oxime reactivators of cyclosarin (GF) inhibited AChE to aid discovery of potential, more efficacious novel non-oxime reactivators

Popis výsledku v původním jazyce

Cyclohexyl methylphosphonofluoridate (cyclosarin, cyclosin, GF) is a highly toxic organophosphorus (OP) nerve agent considered as potential warfare threats and known to be resistant to conventional oxime antidotal therapy. To aid discovery of novel antidotes for GF toxicity, a three-dimensional in silico pharmacophore model for reactivation efficacy against GF intoxication is presented. The model was generated from published experimental percentage reactivation data on oximes as changes of AChE/BuChE activities in the whole blood after cyclosarin intoxication and administration. The generated pharmacophore model was found to contain a hydrogen bond donor site and two ring aromatic sites as necessary optimal features for reactivation of GF intoxication.Stereo-electronic features of oximes reported by us earlier provided guidance to develop the model and were found to be consistent with the reported structure activity data. Furthermore, from virtual screening of two commercial databases

Název v anglickém jazyce

In silico pharmacophore modeling on known pyridinium oxime reactivators of cyclosarin (GF) inhibited AChE to aid discovery of potential, more efficacious novel non-oxime reactivators

Popis výsledku anglicky

Cyclohexyl methylphosphonofluoridate (cyclosarin, cyclosin, GF) is a highly toxic organophosphorus (OP) nerve agent considered as potential warfare threats and known to be resistant to conventional oxime antidotal therapy. To aid discovery of novel antidotes for GF toxicity, a three-dimensional in silico pharmacophore model for reactivation efficacy against GF intoxication is presented. The model was generated from published experimental percentage reactivation data on oximes as changes of AChE/BuChE activities in the whole blood after cyclosarin intoxication and administration. The generated pharmacophore model was found to contain a hydrogen bond donor site and two ring aromatic sites as necessary optimal features for reactivation of GF intoxication.Stereo-electronic features of oximes reported by us earlier provided guidance to develop the model and were found to be consistent with the reported structure activity data. Furthermore, from virtual screening of two commercial databases

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

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Current Computer-Aided Drug Design

ISSN

1573-4099

e-ISSN

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Svazek periodika

9

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

10

Strana od-do

402-411

Kód UT WoS článku

000323931600011

EID výsledku v databázi Scopus

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