J Appl Biomed 4:67-72, 2006 | DOI: 10.32725/jab.2006.006

Reactivation study of pyridinium oximes for acetylcholinesterases inhibited by paraoxon or DFP

Tae-Hyuk Kim¹, Kyung-Ae Oh^1,2, No-Joong Park¹, No-Sang Park¹, Yeong Joon Kim², Eul Kyun Yum², Young-Sik Jung^1,*

¹ Medicinal Science Division, Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Daejeon 305-606, Korea

² Department of Chemistry, Chungnam National University, Yusong, Daejeon 305-764, Korea

We tested the potency to reactivate AChE inhibited by diisopropyl fluorophosphates (DFP) by using bis-pyridinium oxime reactivators connected with CH₂CH₂OCH₂CH₂ linkers between two pyridinium rings. The potency was strongly dependent on oxime functional groups, and the bis-oxime derivatives 1,1-[Oxybis(ethylene)]-bis[4-(hydroxyimino)methyl]pyridinium dibromide (1) and 1,1-[Oxybis(ethylene)]-bis[2-(hydroxyimino)methyl]pyridinium dichloride (2) are more potent than mono-oxime compounds 1-(4-hydroxyiminomethyl-1-pyridino)-5-(4-carbamoyl-1-pyridino)-3-oxapentane dibromide (3) and 1-(3-hydroxyiminomethyl-1-pyridino)-5-(4-carbamoyl-1-pyridino)-3-oxapentane dibromide (4). Not only is the number of oxime groups an important structural factor, but also their position. The in vitro reactivation ability of the most potent bis-pyridinium oxime 2 was further evaluated for the housefly (HF) AChE inhibited by DFP and the bovine red blood cell (RBC) AChE inhibited by paraoxon. The reactivation ability of oxime 2 at 5x10^-3M concentration was almost 80% for HF-AChE inhibited by DFP and 82.1% for RBC-AChE inhibited by paraoxon.

Keywords: Paraoxon; DFP; Organophosphorus agents; Bis-pyridinium oxime reactivators; Acetylcholinesterase

Received: October 30, 2005; Revised: December 14, 2005; Published: July 31, 2006  Show citation