Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugates
نویسندگان
چکیده
منابع مشابه
Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases.
We present a systematic structural optimization of uncharged but ionizable N-substituted 2-hydroxyiminoacetamido alkylamine reactivators of phosphylated human acetylcholinesterase (hAChE) intended to catalyze the hydrolysis of organophosphate (OP)-inhibited hAChE in the CNS. Starting with the initial lead oxime RS41A identified in our earlier study and extending to the azepine analog RS194B, re...
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We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular ...
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Nerve agents are highly toxic organophosphorus compounds with strong inhibition potency against acetylcholinesterase (AChE). Herein, we describe two first extremely promising uncharged reactivators for poisoned human AChE with a superior or similar in vitro ability to reactivate the enzyme as compared to that of HI-6, obidoxime, TMB-4 and HLö-7.
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ژورنال
عنوان ژورنال: Chemico-Biological Interactions
سال: 2013
ISSN: 0009-2797
DOI: 10.1016/j.cbi.2012.08.014