Reactivation of VX-inhibited AChE by novel oximes having two oxygen atoms in the linker

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.