New oxime reactivators connected with CH2O(CH2)nOCH2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase.
New bis-pyridinium oxime reactivators 6 with CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) linkers between the two pyridinium rings were designed and synthesized. In the in vitro test of their potency to reactivate AChE inhibited by organophosphorus agents at 5 x 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.
Yang
Garp Yeol
GY
Drug Discovery Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong, Daejeon 305-600, Republic of Korea.
Oh
Kyung-Ae
KA
Park
No-Joong
NJ
Jung
Young-Sik
YS
D000110:Acetylcholinesterase / Q000737:chemistry / Q000187:drug effects*; D000818:Animals; D002417:Cattle; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D006793:Houseflies; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010261:Paraoxon / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
C526495:1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichloride; D002801:Cholinesterase Reactivators; D003432:Cross-Linking Reagents; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; D010261:Paraoxon