INVESTIGATION OF QUINONE METHIDE PRECURSORS AS REACTIVATORS FOR ORGANOPHOSPHORUS-INHIBITED BUTYRYLCHOLINESTERASE
Loading...
Date
2024-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
This study investigates the potential of quinone methide precursors (QMPs) as reactivators for organophosphorus (OP)-inhibited butyrylcholinesterase (BChE), an enzyme offering protection against OP exposure by sequestering OP compounds. Such OP compounds were initially developed for pest control but have significant inhibitory effects on human acetylcholinesterase (AChE), an enzyme crucial for nervous system function, and human BChE whose role is non-essential in the body. While the inhibition of AChE leads to overstimulation of neural pathways, BChE acts as a potential bioscavenger, offering a line of defense by inactivating OP compounds. This study focuses on expanding the protective capabilities of BChE through the application of quinone methide precursors (QMPs), aiming to enhance BChE's ability to detoxify multiple OP compounds in a pseudo-catalytic manner. Through a series of in vitro experiments, including modified Ellman’s assays and high-throughput screening methods, this research evaluates the efficacy of various QMPs in recovering (reactivating) the native form of BChE after inhibition by different OP compounds. In addition, reactivation kinetics by QMPs are analyzed to understand the interactions and dynamics between QMPs and OP-inhibited BChE, providing insights into the underlying reactivation process. Findings reveal promising reactivation potentials of certain QMPs across diverse OP inhibitors, highlighting the significance of structural and electronic properties of substituents on QMPs for enhanced efficacy. This research not only contributes to advancing therapeutic strategies against OP exposure but also elucidates the structural requirements for the future development of efficient BChE reactivators, paving the way for future in vivo studies and potential clinical applications.
Description
Keywords
Butyrylcholinesterase (BChE) Reactivation, Organophosphorus (OP) Inhibitors, Enzyme Kinetics, Structural Activity Relationship (SAR), Biochemical Defense Mechanisms, In Vitro Efficacy Studies