The bispyridinium-dioxime HLö-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman.
Purification of (+)-tabun was accomplished by treatment with electric eel acetylcholinesterase (AChE) in order to bind contaminating (-)-tabun and with purified (+)-tabun shown similar properties in reactivation reactions with oximes (pH 7.5, 25 degrees). The bispyridinium-2,4-dioxime HLö-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. HLö-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, HLö-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, HLö-7 is the first compound reported in literature that shows a potent reactivating activity towards both tabun-inhibited AChE and soman-inhibited AChE.
de Jong
L P
LP
Prins Maurits Laboratory TNO, Rijswijk, The Netherlands.
Verhagen
M A
MA
Langenberg
J P
JP
Hagedorn
I
I
Löffler
M
M
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002801:Cholinesterase Reactivators; D004524:Eels / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010755:Organophosphates / Q000037:antagonists & inhibitors*; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors*; D010091:Oximes / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012999:Soman / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002801:Cholinesterase Reactivators; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D012999:Soman; D000110:Acetylcholinesterase; C009374:tabun