engleski

Efficiency of novel heterocyclic oximes in reactivation of paraoxon-inhibited cholinesterases

Toxic cholinesterase inhibiting compounds like organophosphates (OP) and carbamates are intensively used and produced troughout the world and continue to be responsible for poisoning and deaths.Chemical warfare agents are of outmost concern due to their possible use in wars and terrorist attacks. Since there is still no single, broad-spectrum compound suitable for the antidotal treatment of poisoning with all OP agents a series of novel aliphatic and aromatic quaternary salts of N- alkyl/aryl imidazol- and benzimidazole-2- aldoximes have been prepared as potential reactivators of inhibited butyrylcholinesterase. N-alkylations of commercially available heterocyclic azoles resulted in their N-alkyl/aryl derivatives. N- alkyl/aryl imidazoles and benzimidazoles were converted to the appropriate 2-carbaldehydes by using modified Ivesen-Lund method and then to 2-aldoximes. Reaction of the oximes with the alkyl/aryl halogenides resulted in a desired quaternary salts. Structures of prepared compounds were deduced from IR, one- and twodimensional NMR and MS spectra. Ellmans method and acetylthiocholine as substrate will be used to test inhibitory properties of prepared compounds and their reactivation efficiency of Paraoxon™ inhibited HuAChE and HuBChE, as well as lyophilised EqBChE and RSBChE. Structural characteristics of an efficient oxime reactivator will be discussed.

oxime ; cholinesterase ; antidote

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