engleski

Synthesis and evaluation of novel analoges of vitamine B6 as reactivators of tabun - and paraoxon-inhibited acetylcholinesterase

A series of novel pyridinium oximes were prepared by reactions of quaternization of pyridoxal oxime with substituted phenacyl bromides in acetone at room temperature and methanol with refluxing. The structures of compounds were determined according to the data obtained by IR-spectroscopy, 1H- and 13C- nuclearmagnetic resonance as well as by elemental analysis. We tested five oximes in 1 mM concentration as reactivators of human erythrocytes acetylcholinesterase (AChE) inhibited by organophosphorus compounds tabun and paraoxon: 1-phenacyl-3-hydroxy-4- hydroxyiminomethyl-5-hydroxymethyl-2- methylpyridinium bromide, 1-(4’ - chlorophenacyl)-3-hydroxy-4-hydroxyiminomethyl- 5-hydroxymethyl-2-methylpyridinium bromide, 1- (4’ -fluorophenacyl)-3-hydroxy-4- hydroxyiminomethyl-5-hydroxymethyl-2- methylpyridinium bromide, 3-hydroxy-4- hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1- (4’ -methylphenacyl) pyridinium bromide, 3- hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2- methyl-1-(4’ -methoxyphenacyl) pyridinium bromide. However, tested oximes were not efficient in reactivation of both tabun and paraoxon inhibited AChE. The maximum restored enzyme activity in 24 h was below 25 %.

pyridoxal oxime ; reactivation ; acetylcholinesterase ; tabun

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