Fluorinated pyridinium oximes as potential reactivators for acetylcholinesterases inhibited by paraoxon organophosphorus agent.
A series of fluorinated oxime compounds was designed and synthesized in order to probe the effect of fluorine substitution on reactivation of inhibited acetylcholinesterase (AChE) by organophosphorus agents. Permeability measurements, using the Parallel Artificial Membrane Permeation Assays (PAMPA) method, were employed to experimentally demonstrate that membrane permeabilities of the series of oximes increase in proportional to the increase in the number of fluorine atoms. Among the compounds explored in this study, the mono-fluorinated carbamoyl aldoxime 4b was the most potent reactivator for paraoxon-inhibited red blood cell (RBC) AChE.
Jeong
Hee Chun
HC
Bio-organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong, Daejeon 305-600, Republic of Korea.
Park
No-Joong
NJ
Chae
Chong Hak
CH
Musilek
Kamil
K
Kassa
Jiri
J
Kuca
Kamil
K
Jung
Young-Sik
YS
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology; D010261:Paraoxon / Q000737:chemistry* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; D010261:Paraoxon