New oxime reactivators connected with CH_2O(CH_2)_nOCH_2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase

摘要

New bis-pyridinium oxime reactivators 6 with CH_2O(CH_2)_2OCH_2 and CH_2O(CH_2)_4OCH_2 linkers between the two pyrid-inium rings were designed and synthesized. In the in vitro test of their potency to reactivate AChE inhibited by organophosphorus agents at 5 × 10~(-3) M concentration, the reactivation ability of 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichloride (6a) was 63% for housefly (HF) AChE inhibited by diisopropyl fluorophosphates (DFP), 51% for bovine red blood cell (RBC) AChE inhibited by DFP, 67% for HF-AChE inhibited by paraoxon, and 81% for RBC-AChE inhibited by paraoxon. Except in the case of DFP-inhibited HF AChE test of 2-PAM, the activities of 6a are much higher than the activities of 2-PAM and HI-6 which are AChE reactivators currently in use.