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Efficiency of imidazolium based oximes in reactivation of organophosphorus compound‐ inhibited cholinesterases

We investigated efficiency of novel imidazolium and benzimidazolium oximes to reactivate organophosphorus compounds paraoxon‐, VX‐, and tabun‐inhibited cholinesterases (ChEs). Their antidotal potency, expressed in terms of the observed reactivation rate constant (kobs ), was compared with the potency of HI‐6 and obidoxime, used in medical practice today. None of the tested oximes showed overall improvement in the reactivation of OP‐inhibited AChE, however, several oximes were pointed out as leads in the case of OP‐inhibited BChE reactivation. A comprehensive analysis was performed for the most promising oximes defining all relevant kinetic parameters of reactivation as well as interactions with uninhibited ChEs. Considering the strict criteria set for in vivo applications, we determined cytotoxicity of lead oximes on two cell lines, as well as ex vivo bioscavenging capacities of BChE‐oxime pairs. Furthermore, experimental data were correlated with computational studies including QSAR analysis as a starting point in further oximes’ structure refinement. Obtained overall profiles of lead oximes allow potential in vivo tests in development of BChE based OP‐ bioscavengers. Supported by the CSF 4307.

paraoxon ; tabun ; VX ; HI-6 ; obidoxime

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