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

Kamil Kuca; Jiri Cabal; Daniel Jun; Kamil Musilek; Ondrej Soukup; Miroslav Pohanka; Jaroslav Pejchal; Kyung-Ae Oh; Garp Yeol Yang; Young-Sik Jung

doi:10.1016/j.etap.2010.03.011

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

Environ Toxicol Pharmacol. 2010 Jul;30(1):85-7. doi: 10.1016/j.etap.2010.03.011. Epub 2010 Mar 17.

Authors

Kamil Kuca¹, Jiri Cabal, Daniel Jun, Kamil Musilek, Ondrej Soukup, Miroslav Pohanka, Jaroslav Pejchal, Kyung-Ae Oh, Garp Yeol Yang, Young-Sik Jung

Affiliation

¹ Center of Advanced Studies, Hradec Kralove, Czech Republic; Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.

PMID: 21787634
DOI: 10.1016/j.etap.2010.03.011

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.