Dual acting oximes designed for therapeutic decontamination of reactive organophosphates via catalytic inactivation and acetylcholinesterase reactivation.

ABSTRACT: A conventional approach in the therapeutic decontamination of reactive organophosphate (OP) relies on chemical OP degradation by oxime compounds. However, their efficacy is limited due to their lack of activity in the reactivation of acetylcholinesterase (AChE), the primary target of OP. Here, we describe a set of α-nucleophile oxime derivatives which are newly identified for such dual modes of action. Thus, we prepared a 9-member oxime library, each composed of an OP-reactive oxime core linked to an amine-terminated scaffold, which varied through an N-alkyl functionalization. This library was screened by enzyme assays performed with human and electric eel subtypes of OP-inactivated AChE, which led to identifying three oxime leads that displayed significant enhancements in reactivat

SUBMITTER: Cannon J 

PROVIDER: S-EPMC8459330 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature