Mechanistic Insights into Enhanced Reactivation of Organophosphate-Inhibited Enzymes by Methyl-Substituted 2-Pralidoxime Analogs.

ABSTRACT: Organophosphate (OP) compounds, such as paraoxon (POX), inhibit enzymes critical for neurotransmission, causing severe neurotoxic effects. Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM is commonly employed to reverse this inhibition, but its reactivation efficiency is limited. This study computationally explores the reactivation mechanisms of 2-PAM and its methyl-substituted analogs, 4-methyl-2-PAM (4-Met-2-PAM), and 4,6-dimethyl-2-PAM (4,6-Dimet-2-PAM). The reactivation process involves several key steps, such as hydrogen transfer and nucleophilic substitution (S_N2). Introducing methyl groups at positions 4 and 6 increases the negative charge on the oxime oxygen, improving nucleophilicity and reactivity. Both 4-Met-2-PAM and 4,6-Dimet-2-PAM show better react

SUBMITTER: Naweephattana P 

PROVIDER: S-EPMC12169655 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature