Synthesis and evaluation of novel analogues of vitamin B6 as reactivators of tabun and paraoxon inhibited acetylcholinesterase
A series of novel pyridinium oximes was prepared by reactions of quaternization of pyridoxal oxime with substituted phenacyl bromides in acetone at room temperature. The structures of compounds were determined according to the data obtained by IR spectroscopy, mass spectrometry, (1)H and (13)C nucle...
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Published in | Chemico-biological interactions Vol. 187; no. 1-3; pp. 234 - 237 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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Abstract | A series of novel pyridinium oximes was prepared by reactions of quaternization of pyridoxal oxime with substituted phenacyl bromides in acetone at room temperature. The structures of compounds were determined according to the data obtained by IR spectroscopy, mass spectrometry, (1)H and (13)C nuclear magnetic resonance spectroscopy as well as by elemental analysis. We tested pyridoxal oxime (1) and five prepared oximes in 1mM 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 (2), 1-(4'-chlorophenacyl)-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (3), 1-(4'-fluorophenacyl)-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (4), 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(4'-methylphenacyl)pyridinium bromide (5), 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(4'-methoxyphenacyl)pyridinium bromide (6). However, tested oximes were not efficient in reactivation of either tabun or paraoxon inhibited AChE. The maximum restored enzyme activity in 24h was below 25%. Therefore, this class of compounds cannot be considered as potential improvement in a search for new and more efficient antidotes against OP poisoning. |
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AbstractList | A series of novel pyridinium oximes was prepared by reactions of quaternization of pyridoxal oxime with substituted phenacyl bromides in acetone at room temperature. The structures of compounds were determined according to the data obtained by IR spectroscopy, mass spectrometry, (1)H and (13)C nuclear magnetic resonance spectroscopy as well as by elemental analysis. We tested pyridoxal oxime (1) and five prepared oximes in 1mM 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 (2), 1-(4'-chlorophenacyl)-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (3), 1-(4'-fluorophenacyl)-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (4), 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(4'-methylphenacyl)pyridinium bromide (5), 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(4'-methoxyphenacyl)pyridinium bromide (6). However, tested oximes were not efficient in reactivation of either tabun or paraoxon inhibited AChE. The maximum restored enzyme activity in 24h was below 25%. Therefore, this class of compounds cannot be considered as potential improvement in a search for new and more efficient antidotes against OP poisoning. |
Author | Kovac, Spomenka Katalinić, Maja Kovarik, Zrinka Gaso-Sokac, Dajana Busić, Valentina |
Author_xml | – sequence: 1 givenname: Dajana surname: Gaso-Sokac fullname: Gaso-Sokac, Dajana email: dajana.gaso@ptfos.hr organization: Department of Chemistry, J.J. Strossmayer University of Osijek, Kuhaceva 20, HR-31000 Osijek, Croatia. dajana.gaso@ptfos.hr – sequence: 2 givenname: Maja surname: Katalinić fullname: Katalinić, Maja – sequence: 3 givenname: Zrinka surname: Kovarik fullname: Kovarik, Zrinka – sequence: 4 givenname: Valentina surname: Busić fullname: Busić, Valentina – sequence: 5 givenname: Spomenka surname: Kovac fullname: Kovac, Spomenka |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20144593$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Acetylcholinesterase - metabolism Cholinesterase Inhibitors - pharmacology Cholinesterase Reactivators - chemical synthesis Cholinesterase Reactivators - chemistry Cholinesterase Reactivators - pharmacology Enzyme Activation - drug effects Humans Organophosphates - pharmacology Oximes - chemical synthesis Oximes - chemistry Oximes - pharmacology Paraoxon - pharmacology Vitamin B 6 - analogs & derivatives Vitamin B 6 - chemical synthesis Vitamin B 6 - pharmacology |
Title | Synthesis and evaluation of novel analogues of vitamin B6 as reactivators of tabun and paraoxon inhibited acetylcholinesterase |
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