Novel series of bispyridinium compounds bearing a (Z)-but-2-ene linker—Synthesis and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase
2007; Elsevier BV; Volume: 17; Issue: 11 Linguagem: Inglês
10.1016/j.bmcl.2007.03.025
ISSN1464-3405
AutoresKamil Musílek, Ondřej Holas, Kamil Kuča, Daniel Jun, Vlastimil Dohnal, Veronika Opletalová, Martin Doležal,
Tópico(s)Cholinesterase and Neurodegenerative Diseases
ResumoSix novel AChE reactivators with a (Z)-but-2-ene linker were synthesized using the known synthetic pathways. Their ability to reactivate AChE, which had been previously inhibited by nerve agent tabun or pesticide paraoxon, was tested in vitro and compared to pralidoxime, HI-6, obidoxime, and K075. The novel synthesized compounds were found to be ineffective against GA-inhibited AChE but the ability of (Z)-1,4-bis(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide to reactivate paraoxon-inhibited AChE was comparable with that of oxime K075. Notably, the oxime group in position four substantially increased the ability of the novel compounds to reactivate paraoxon-inhibited AChE.
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