Assessment of antidotal efficacy of cholinesterase reactivators against paraoxon: In vitro reactivation kinetics and physicochemical properties

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F14%3A10281225" target="_blank" >RIV/00179906:_____/14:10281225 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62690094:18470/14:50002647

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0960894X14008300" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0960894X14008300</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmcl.2014.07.095" target="_blank" >10.1016/j.bmcl.2014.07.095</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Assessment of antidotal efficacy of cholinesterase reactivators against paraoxon: In vitro reactivation kinetics and physicochemical properties

Popis výsledku v původním jazyce

The search of proficient oximes as reactivators of irreversibly inhibited-AChE by organophosphate poisoning necessitates an appropriate assessment of their physicochemical properties and reactivation kinetics. Therefore, herein acid dissociation constant; pKa, lipophilicity; logP, polar surface area, hydrogen bond donor and acceptor counts of structurally different oximes (two tertiary oximes and thirteen pyridinium aldoxime derivatives) have been evaluated. The experimentally obtained data for pKa hasbeen comparatively analyzed by using non-linear regression. Further the tested oximes were screened through in vitro reactivation kinetics against paraoxon-inhibited AChE. The pKa values of all the examined oximes were within the range of 7.50-9.53. pKavalues of uncharged and mono-pyridinium oximes were in good correlation with their reactivation potency. The high negative logP values of pyridinium oxime reactivators indicate their high hydrophilic character; hence oximes with improved

Název v anglickém jazyce

Assessment of antidotal efficacy of cholinesterase reactivators against paraoxon: In vitro reactivation kinetics and physicochemical properties

Popis výsledku anglicky

The search of proficient oximes as reactivators of irreversibly inhibited-AChE by organophosphate poisoning necessitates an appropriate assessment of their physicochemical properties and reactivation kinetics. Therefore, herein acid dissociation constant; pKa, lipophilicity; logP, polar surface area, hydrogen bond donor and acceptor counts of structurally different oximes (two tertiary oximes and thirteen pyridinium aldoxime derivatives) have been evaluated. The experimentally obtained data for pKa hasbeen comparatively analyzed by using non-linear regression. Further the tested oximes were screened through in vitro reactivation kinetics against paraoxon-inhibited AChE. The pKa values of all the examined oximes were within the range of 7.50-9.53. pKavalues of uncharged and mono-pyridinium oximes were in good correlation with their reactivation potency. The high negative logP values of pyridinium oxime reactivators indicate their high hydrophilic character; hence oximes with improved

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

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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

Bioorganic and Medicinal Chemistry Letters

ISSN

0960-894X

e-ISSN

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Svazek periodika

24

Číslo periodika v rámci svazku

19

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

4743-4748

Kód UT WoS článku

000342574600024

EID výsledku v databázi Scopus

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