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

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.