Encapsulation of oxime acetylcholinesterase reactivators: influence of physiological conditions on the stability of oxime-cucurbit[7]uril complexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50016981" target="_blank" >RIV/62690094:18470/20:50016981 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/20:00556107

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2020/NJ/D0NJ03102J#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2020/NJ/D0NJ03102J#!divAbstract</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d0nj03102j" target="_blank" >10.1039/d0nj03102j</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Encapsulation of oxime acetylcholinesterase reactivators: influence of physiological conditions on the stability of oxime-cucurbit[7]uril complexes

Popis výsledku v původním jazyce

Oxime-based acetylcholinesterase reactivators are a specific group of drugs used for the treatment of organophosphate intoxication. However, high hydrophilicity and poor blood-brain barrier penetration limit their physiological potential. Cucurbit[7]urile (CB[7]) was used in this work as a potential carrier of oxime molecules to increase their treatment effectiveness. The host-guest chemistry of CB[7] with five clinically used oximes (trimedoxime, asoxime, obidoxime, pralidoxim and methoxime) and two new pre-clinical oximes (K027 and K048) was characterized under simulated physiological conditions using titration experiments with UV-vis detection. CB[7] forms stable complexes of 1 : 1 stoichiometry with all tested oximes. The decrease of complex stability was observed at a pH above the pK(a)of oxime, which limits the applicability of the complexation for oximes with pK(a)below the physiological pH. The combination of physiological ionic strength and pH causes partial decrease of the complex stability. The effect of organic solvent used in the sample pretreatment step before spectral analysis of oxime-CB[7] complexes in biological samples was demonstrated. Methanol is a more suitable solvent with low effect on complex stability. Finally, the ability of mass spectrometry with electrospray ionization was demonstrated for the analysis of oxime-CB[7] complexes.

Název v anglickém jazyce

Encapsulation of oxime acetylcholinesterase reactivators: influence of physiological conditions on the stability of oxime-cucurbit[7]uril complexes

Popis výsledku anglicky

Oxime-based acetylcholinesterase reactivators are a specific group of drugs used for the treatment of organophosphate intoxication. However, high hydrophilicity and poor blood-brain barrier penetration limit their physiological potential. Cucurbit[7]urile (CB[7]) was used in this work as a potential carrier of oxime molecules to increase their treatment effectiveness. The host-guest chemistry of CB[7] with five clinically used oximes (trimedoxime, asoxime, obidoxime, pralidoxim and methoxime) and two new pre-clinical oximes (K027 and K048) was characterized under simulated physiological conditions using titration experiments with UV-vis detection. CB[7] forms stable complexes of 1 : 1 stoichiometry with all tested oximes. The decrease of complex stability was observed at a pH above the pK(a)of oxime, which limits the applicability of the complexation for oximes with pK(a)below the physiological pH. The combination of physiological ionic strength and pH causes partial decrease of the complex stability. The effect of organic solvent used in the sample pretreatment step before spectral analysis of oxime-CB[7] complexes in biological samples was demonstrated. Methanol is a more suitable solvent with low effect on complex stability. Finally, the ability of mass spectrometry with electrospray ionization was demonstrated for the analysis of oxime-CB[7] complexes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/GA18-08937S" target="_blank" >GA18-08937S: Výzkum oxim-CB(7) komplexů při prostupu kvarterních reaktivátorů acetylcholinesterasy do centrálního nervového systému</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

New journal of chemistry

ISSN

1144-0546

e-ISSN

—

Svazek periodika

44

Číslo periodika v rámci svazku

34

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

6

Strana od-do

14367-14372

Kód UT WoS článku

000564479900005

EID výsledku v databázi Scopus

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