title: New group of xylene linker-containing acetylcholinesterase reactivators as antidotes against the nerve agent cyclosarin.
abstract: Nerve agents such as sarin, cyclosarin and tabun are organophosphorus substances able to inhibit the enzyme acetylcholinesterase (AChE; EC 3.1.1.7). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None of the known AChE reactivators is able to reactivate AChE inhibited by all nerve agents used. In this work, reactivation potency of nine newly developed AChE reactivators with an incorporated xylene ring in their structure was measured in vitro. Cyclosarin was chosen as an appropriate member of the nerve agent family. Reactivation potency of the tested AChE reactivators was compared with the gold standard of AChE reactivators--pralidoxime. Two oximes (K107 and K108) surpassed the reactivation potency of pralidoxime. Moreover, from the obtained results it could be deduced that AChE reactivators with a functional oxime group in position-2 are the most potent AChE reactivators in the case of cyclosarin intoxications.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Hrabinova
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000737:chemistry* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000931:Antidotes; D002800:Cholinesterase Inhibitors; D003432:Cross-Linking Reagents; D009943:Organophosphorus Compounds; D010091:Oximes; D014992:Xylenes; D000110:Acetylcholinesterase; C053914:cyclohexyl methylphosphonofluoridate