title: Reactivation of VX-inhibited AChE by novel oximes having two oxygen atoms in the linker.
abstract: Two newly developed AChE reactivators possessing two oxime groups in 4-position of the pyridinium rings with linkers CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) were tested for their potency to reactivate VX-inhibited AChE. Their reactivation potency was compared with currently available oximes such as pralidoxime, obidoxime and HI-6. Appropriate constants (affinity towards the intact and inhibited enzyme, reactivation rate) characterizing the reactivation process were determined. According to the data obtained, a new oxime with CH(2)O(CH(2))(2)OCH(2) linker reached as high reactivation potency as HI-6. The percentage of reactivation of the oxime with CH(2)O(CH(2))(2)OCH(2) linker was comparable to that of obidoxime at a concentration 10(-3)M. Hence, these oximes may be worthy of future development for the treatment of nerve agent intoxications, especially, with lipophilic agents such as soman and cyclosarin.
authors.affiliation: Center of Advanced Studies, Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Cabal
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Ondrej
authors.initials: O
authors.lastname: Soukup
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pejchal
authors.forename: Kyung-Ae
authors.initials: KA
authors.lastname: Oh
authors.forename: Garp Yeol
authors.initials: GY
authors.lastname: Yang
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Jung