title: Monooxime Bispyridinium Reactivators Bearing Xylene Linker Synthesis and In Vitro Evaluation on Model of Organophosphate-Inhibited Acetylcholinesterase.
abstract: Nine novel mono-oxime reactivators bearing xylene linker were synthesized in an effort to improve previously prepared xylene bisoximes and monocarbamoyl-monooximes. The novel compounds were tested in vitro on the model of tabun-, paraoxon-, methylparaoxon- and DFP-inhibited human erythrocyte AChE. Their reactivation ability was compared to pralidoxime, asoxime, obidoxime and two previously prepared xylene linked bisoximes (K107, K108). All compounds showed minimal reactivation of tabun-inhibited AChE at selected concentration scale. This finding was explained by molecular modelling study. Bisoximes obidoxime and K108 resulted as the best reactivators for paraoxon-, methylparaoxon- and DFP-inhibited AChE. The loss of nonoxime moiety lead to the loss of reactivation ability within the novel compounds. Though the novel reactivators did not exceed previously known compounds, they confirmed former SAR findings for xylene-linked AChE reactivators.
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Jan
authors.initials: J
authors.lastname: Hambalek
authors.forename: Ondrej
authors.initials: O
authors.lastname: Holas
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Dohnal
authors.affiliation: Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic. kamil.kuca@fnhk.cz.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
mesh_terms: D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis / Q000737:chemistry*; D057075:Enzyme Assays; D062105:Molecular Docking Simulation; D010755:Organophosphates / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014992:Xylenes / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D014992:Xylenes