Pralidoxime-like reactivator with increased lipophilicity - Molecular modeling and in vitro study
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
37788753
DOI
10.1016/j.cbi.2023.110734
PII: S0009-2797(23)00401-5
Knihovny.cz E-zdroje
- Klíčová slova
- 2-PAM, Antidote, Nerve agent, Pesticide, Reactivator,
- MeSH
- acetylcholinesterasa metabolismus MeSH
- antidota farmakologie MeSH
- cholinesterasové inhibitory farmakologie metabolismus MeSH
- lidé MeSH
- otrava organofosfáty * MeSH
- oximy farmakologie chemie MeSH
- pralidoximové sloučeniny farmakologie MeSH
- reaktivátory cholinesterasy * chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- antidota MeSH
- cholinesterasové inhibitory MeSH
- oximy MeSH
- pralidoxime MeSH Prohlížeč
- pralidoximové sloučeniny MeSH
- reaktivátory cholinesterasy * MeSH
Acetylcholinesterase (AChE, EC 3.1.1.7) reactivators (2-PAM, trimedoxime, obidoxime, asoxime) have become an integral part of antidotal treatment in cases of nerve agent and organophosphorus (OP) pesticide poisonings. They are often referred to as specific antidotes due to their ability to restore AChE function when it has been covalently inhibited by an OP compound. Currently available commercial reactivators exhibit limited ability to penetrate the blood-brain barrier, where reactivation of inhibited AChE is crucial. Consequently, there have been numerous efforts to discover more brain-penetrating AChE reactivators. In this study, we examined a derivative of 2-PAM designed to possess increased lipophilicity. This enhanced lipophilicity was achieved through the incorporation of a benzyl group into its molecular structure. Initially, a molecular modeling study was conducted, followed by a comparison of its reactivation efficacy with that of 2-PAM against 10 different AChE inhibitors in vitro. Unfortunately, this relatively significant structural modification of 2-PAM resulted in a decrease in its reactivation potency. Consequently, this derivative cannot be considered as a broad-spectrum AChE reactivator.
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