In vitro oxime-assisted reactivation of paraoxon-inhibited human acetylcholinesterase and butyrylcholinesterase
Language English Country England, Great Britain Media print
Document type Journal Article
- MeSH
- Acetylcholinesterase metabolism MeSH
- Antidotes chemistry pharmacology MeSH
- Cholinesterase Inhibitors toxicity MeSH
- Erythrocytes drug effects enzymology MeSH
- Cells, Cultured MeSH
- Quantitative Structure-Activity Relationship MeSH
- Humans MeSH
- Molecular Structure MeSH
- Paraoxon toxicity MeSH
- Cholinesterase Reactivators chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholinesterase MeSH
- Antidotes MeSH
- Cholinesterase Inhibitors MeSH
- Paraoxon MeSH
- Cholinesterase Reactivators MeSH
INTRODUCTION: Organophosphorus pesticides and nerve agents are highly toxic to humans and other living organisms, primarily because of their interaction with enzyme acetylcholinesterase. The aim of our study was to find suitable reactivators of acetylcholinesterase and butyrylcholinesterase and to recommend the most efficacious compounds for the next evaluation as antidotes for intoxication by pesticides. METHODS: Eighteen structurally different oxime reactivators were tested for their in vitro ability to reactivate paraoxon-inhibited human erythrocyte acetylcholinesterase and human plasma butyrylcholinesterase to find out structure-activity relationship within this set of compounds. Their reactivation ability was compared with commercially available acetylcholinesterase reactivators (pralidoxime, methoxime, trimedoxime, obidoxime, and HI-6). RESULTS AND DISCUSSION: The best reactivation ability was achieved with obidoxime, trimedoxime, compounds K027, K075, K203, and K048. We have also tested reactivation of butyrylcholinesterase with the aim to recommend an efficient reactivator, able to perform a "pseudo catalytic" bioscavenger with butyrylcholinesterase, which is developed as new antidote of organophosphate poisonings. Such combination could allow an enhancement of prophylactic and therapeutic efficiency of administered enzyme. Compounds K117, K269, K075, and trimedoxime were found to be the most potent reactivators of inhibited butyrylcholinesterase. CONCLUSIONS: In this work, we have evaluated only reactivation of paraoxon-inhibited cholinesterases. To get better understanding of this problem, a larger number of organophosphorus inhibitors should be used.
References provided by Crossref.org
Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016-2019)