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.
Six 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.
Musilek
Kamil
K
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Holas
Ondrej
O
Kuca
Kamil
K
Jun
Daniel
D
Dohnal
Vlastimil
V
Opletalova
Veronika
V
Dolezal
Martin
M
D000110:Acetylcholinesterase / Q000187:drug effects; D002073:Butanes / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D010755:Organophosphates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010261:Paraoxon / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C521576:1,4-bis(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide; D002073:Butanes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; C518856:K075 compound; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; D010261:Paraoxon; C009374:tabun