The bispyridinium-dioxime HLö-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman
article
Purification of (+)-tabun was accomplished by treatment with electric eel acetylcholinesterase (AChE) in order to bind contaminating (-)-tabun, the more potent enantiomer with respect of AChE inhibition. Electric eel AChE inhibited with (-)-tabun and with purified (+)-tabun show similar properties in reactivation reactions with oximes (pH 7.5, 25°). The bispyridinium-2,4-dioxime HLo-7 is a substantially active reactivator for these inhibited enzymes as well as for human erythrocyte AChE inhibited with (-)-tabun. In contrast, the corresponding bispyridinium-2-monooxime HI-6 does not show any activity at similar reaction conditions. HLo-7 is also much more active than HI-6 when used as a reactivator for electric eel AChE inhibited by some N-unsubstituted derivatives of tabun. Surprisingly, HLo-7 is highly active in reactivating human erythrocyte and rat diaphragm AChE inhibited by C(+)P(±)- and C(-)P(±)-soman, i.e. at least as active as HI-6, which is the most potent reactivator for soman-inhibited AChE reported so far. To our knowledge, HLo-7 is the first compound reported in literature that shows a potent reactivating activity towards both tabun-inhibited AChE and soman-inhibited AChE.
Topics
Bis(pyridinium oxime) derivativeEnzyme inhibitorOrganophosphorus compoundRadioisotopeEnzyme reactivationFishHumanNonbiological modelNonhumanNormal humanRatStereoisomerismAcetylcholinesterase 9000-81-1AnimalCholinesterase ReactivatorsEelsHumanIn VitroOrganophosphorus CompoundsOximesPhosphoric Acid EstersPyridinesPyridinium CompoundsStereoisomerismStructure-Activity RelationshipOrganophosphorus compoundsOximesPhosphoric acid estersPyridinesPyridinium compoundsSoman, 96-64-0Tabun, 77-81-6
TNO Identifier
230839
ISSN
0006-2952
Source
Biochemical Pharmacology, 38(4), pp. 633-640.
Pages
633-640
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