Reactivation Potential of Novel More Lipophilic Pralidoxime Analogs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014451" target="_blank" >RIV/62690094:18470/18:50014451 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/18:10376449 RIV/60162694:G44__/18:43889544 RIV/61988987:17110/18:A1901RUH

Výsledek na webu

<a href="http://dx.doi.org/10.2174/1570180814666171013163019" target="_blank" >http://dx.doi.org/10.2174/1570180814666171013163019</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570180814666171013163019" target="_blank" >10.2174/1570180814666171013163019</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Reactivation Potential of Novel More Lipophilic Pralidoxime Analogs

Popis výsledku v původním jazyce

Background: Novel, more lipophilic analogs of pralidoxime - 2-PAM (K347, K087) and 4-PAM (K349, K120) have been tested in this study due to the recently discovered fact that monoquaternary AChE reactivators penetrate BBB in higher amount. In vitro tests were run against the several organophosphorus agents including tabun, sarin, cyclosarin, soman, VX-agent, Russian VX-agent, diisopropylfluorophosphate and chlorpyrifos. Methods: Standard potentiometric method was used for the evaluation of reactivation efficacy. Rat brain homogenate was used as the source of acetylcholinesterase. Results: The efficacy of novel reactivators was compared against standard AChE reactivators (2-PAM and 4-PAM). K349 and K120 (10-3 M) were 1.1 and 4.8-fold more effective in the reactivation of sarin-inhibited AChE compared with 4-PAM, respectively. Moreover, K120 in 105 M concentration, which is attainable in the plasma within antidotal treatment of intoxication, was 2.1-fold more effective than standard. Generally, the best results were observed for oxime K120. Conclusion: None of the newly prepared benzylated 2-PAM and 4-PAM analogs showed such a broad spectrum of action as standard pralidoxime.

Název v anglickém jazyce

Reactivation Potential of Novel More Lipophilic Pralidoxime Analogs

Popis výsledku anglicky

Background: Novel, more lipophilic analogs of pralidoxime - 2-PAM (K347, K087) and 4-PAM (K349, K120) have been tested in this study due to the recently discovered fact that monoquaternary AChE reactivators penetrate BBB in higher amount. In vitro tests were run against the several organophosphorus agents including tabun, sarin, cyclosarin, soman, VX-agent, Russian VX-agent, diisopropylfluorophosphate and chlorpyrifos. Methods: Standard potentiometric method was used for the evaluation of reactivation efficacy. Rat brain homogenate was used as the source of acetylcholinesterase. Results: The efficacy of novel reactivators was compared against standard AChE reactivators (2-PAM and 4-PAM). K349 and K120 (10-3 M) were 1.1 and 4.8-fold more effective in the reactivation of sarin-inhibited AChE compared with 4-PAM, respectively. Moreover, K120 in 105 M concentration, which is attainable in the plasma within antidotal treatment of intoxication, was 2.1-fold more effective than standard. Generally, the best results were observed for oxime K120. Conclusion: None of the newly prepared benzylated 2-PAM and 4-PAM analogs showed such a broad spectrum of action as standard pralidoxime.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA15-16701S" target="_blank" >GA15-16701S: Koncept nekvarterních reaktivátorů AChE jakožto antidot otrav organofosfáty - nová naděje či slepá cesta?</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Letters in drug design &amp; discovery

ISSN

1570-1808

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

6

Strana od-do

822-827

Kód UT WoS článku

000436085100002

EID výsledku v databázi Scopus

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