ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 4 (2006), No 2, p 67-72

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

Tae-Hyuk Kim, Kyung-Ae Oh No-Joong Park, No-Sang Park, Yeong Joon Kim, Eul Kyun Yum, and Young-Sik Jung

Address: Young-Sik Jung, Medicinal Science Division, Korea Research Institute of Chemical Technology, P. O. Box 107, Yusong, Daejeon 305-606, Korea

Received 30th October 2005.
Revised 14th December 2005.
Published online 20th February 2006.

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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 bisoxime 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 bispyridinium 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 RB-CAChE inhibited by paraoxon.

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

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