title: Potency of novel oximes to reactivate sarin inhibited human cholinesterases.
abstract: Class of monoquaternary pyridinium oximes was in vitro tested as potential reactivators of acetylcholinesterase (AChE; EC 3.1.1.7) inhibited by nerve agent sarin. Human brain homogenate was used as an appropriate source of cholinesterases. Reactivation potency of novel oximes was compared with currently available reactivators - pralidoxime, obidoxime, and HI-6. According to the obtained results, only five reactivators were able to satisfactorily renew cholinesterase potency (pralidoxime, obidoxime, HI-6, 4-PAM, and K119). Unfortunately, none of the novel tested reactivators surpassed the reactivation potency of the currently most promising reactivator, HI-6. This study shows that monoquaternary reactivators are unable to reactivate nerve agent-inhibited AChE. Due to this, in future, only bisquaternary compounds derived from HI-6 or obidoxime should be designed as new potential cholinesterase reactivators.
authors.affiliation: Center of Advanced Studies, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jan
authors.initials: J
authors.lastname: Picha
authors.forename: Vit
authors.initials: V
authors.lastname: Koleckar
authors.forename: Jan
authors.initials: J
authors.lastname: Marek
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000931:Antidotes / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D009768:Obidoxime Chloride / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D012524:Sarin / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: C505765:4-hydroxyiminomethyl-1-methylpyridinium iodide; D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D012524:Sarin; D000110:Acetylcholinesterase; C022870:asoxime chloride; C028797:pralidoxime