title: Design of a potent reactivator of tabun-inhibited acetylcholinesterase--synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203).
abstract: Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Among the organophosphates, with the exception of soman, tabun (GA) intoxications are the least responsive to treatment with commercially available therapeutics. A rational design was used to increase reactivation ability and decrease the toxicity of the novel reactivator. (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203) has better properties than previously tested compounds in vitro and, therefore, is a potential candidate for the treatment of GA intoxication in vivo.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Hradec Kralove, CZ.
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Jiri
authors.initials: J
authors.lastname: Cabal
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Frank
authors.initials: F
authors.lastname: Gunn-Moore
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D002619:Chemical Warfare Agents / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D007700:Kinetics; D010755:Organophosphates / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; C009374:tabun