Čes. slov. farm. 2006, 55(3):115-119

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

K. Musílek¹, K. Kuča², D. Jun², V. Dohnal³, T-H. Kim⁴, Y.-S. Jung⁴, M. Doležal¹

¹ Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové, Katedra farmaceutické chemie a kontroly léčiv

² Fakulta vojenského zdravotnictví Univerzity obrany Hradec Králové, Katedra toxikologie

³ Mendelova zemědělská a lesnická univerzita Brno, Ústav technologie potravin

⁴ Medicinal Science Division, Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Taejon 05-606, Korea

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.

Keywords: organophosphate; pesticide; acetylcholinesterase; reactivation; in vitro

Received: January 5, 2006; Accepted: February 23, 2006; Published: March 1, 2006  Show citation