engleski

Oxime-assisted reactivation of phosphorylated butyrylcholinesterase

Butyrylcholinesterase is considered an endogenous stoichiometric bioscavenger of organophosphorus compounds (OP), but due to a limited concentration of BChE in the organism, a stoichiometric reduction of OP is not always sufficient. This can be improved by creating a pseudo-catalytic scavenger adding oximes as reactivators of inhibited BChE. In order to improve BChE endogenous bioscavenging function in tabun and paraoxon poisoning, we tested in vitro reactivation of phosphorylated human plasma BChE by eleven bispyridinium oximes varying in the length and type of the linker between rings, and in the position of the oxime group on the ring. Among the tested oximes the most potent reactivators of tabun inhibitedBChE were K117 [1, 1'-(2, 2'-oxybis(ethane-2, 1-diyl))bis(4-hydroxyiminomethyl pyridinium) bromide] and K127 [4-carbamoyl-1-(2-(2-(4-(hydroxyiminomethyl) pyridinium-1-yl)ethoxy)ethyl)pyridinium bromide]. Reactivation by these oximes (1 mM) reached about 50 % after only 20 min, but reactivation stopped at 70 %. Reactivation of paraoxon-inhibited BChE was slow by all of the selected oximes. Using molecular mechanics we performed docking of the oximes to tabun- and paraoxon-inhibited BChE. We will discuss possible structural modifications of bispyridinium oximes to improve reactivation of phosphorylated BChE.

Reactivators; Oximes; Tabun; Inhibition; Butylcholinesterase

nije evidentirano