Synthesis of the novel series of bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase.
Six potential AChE reactivators were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by insecticide chlorpyrifos was tested in vitro. According to the results, (E)-1-(2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide seems to be the most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as constitution of the linking chain between both pyridinium rings, position of the oxime moiety at the pyridinium ring and presence of quaternary nitrogens.
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.
Kuca
Kamil
K
Jun
Daniel
D
Dohnal
Vlastimil
V
Dolezal
Martin
M
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D004390:Chlorpyrifos / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis / Q000494:pharmacology*; D009584:Nitrogen / Q000737:chemistry; D010091:Oximes / Q000737:chemistry; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
C508944:(E)-1-(2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D006842:Hydrocarbons, Brominated; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; D004390:Chlorpyrifos; D009584:Nitrogen