Synthesis of Reactivators of Phosphorylated Acetylcholinesterase of bis-Pyridiniumdialdoxime Type
with a 3-Oxapentane Connecting Chain and Their Testing in vitro on a Model of the Enzyme Inhibited
by Chlorpyrifos and Methylchlorpyrifos
MUSÍLEK K.1, KUČA K.2, JUN D.2, DOHNAL V.3., KIM T-H.4, JUNG Y-S.4, DOLEŽAL M.1
1Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, Katedra farmaceutické chemie a kontroly léčiv 2Fakulta vojenského zdravotnictví Univerzity obrany Hradec Králové, Katedra toxikologie 3Mendelova zemědělská a lesnická univerzita Brno, Ústav technologie potravin 4Medicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yusong, Taejon 05-606, Korea |
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Summary:
Insecticides (e.g., parathion, chlorpyrifos, methylchlorpyrifos) and nerve agents (e.g., soman, sarin, tabun, VX)
belong to the group of organophosphates. They are able to irreversibly inhibit the enzyme acetylcholinesterase
(AChE). Three new reactivators with a 3-oxapentane connecting chain were prepared. The ability of the new
compounds to reactivate AChE inhibited by pesticides was tested in vitro and compared to known oximes
(pralidoxime, methoxime, trimedoxime, obidoxime, HI-6). The results show that the new substances are
superior to known reactivators in the case of methylchlorpyrifos-inhibited AChE at a concentration of 10-3 M
which is unfortunately not applicable to in vivo experiments. All tested compounds are practically ineffective for
methylchlorpyrifos-inhibited AChE at the physiological concentration (10-5 M). On the other hand, the known
reactivators surpass new substances in the case of chlorpyrifos-inhibited AChE at both concentrations.
Key words:
organophosphate – pesticide – acetylcholinesterase – reactivation – in vitro
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