Pralidoxime-like reactivator with increased lipophilicity - Molecular modeling and in vitro study.
Chem Biol Interact
; 385: 110734, 2023 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-37788753
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Reactivadores de la Colinesterasa
/
Intoxicación por Organofosfatos
Límite:
Humans
Idioma:
En
Revista:
Chem Biol Interact
Año:
2023
Tipo del documento:
Article
Pais de publicación:
Irlanda