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• W2063062145 abstract "Organophosphorus nerve agents (OPNAs) are highly toxic compounds that represent a threat to both military and civilian populations. They cause an irreversible inhibition of acetylcholinesterase (AChE), by the formation of a covalent P–O bond with the catalytic serine. Among the present treatment of nerve agents poisoning, pyridinium and bis-pyridinium aldoximes are used to reactivate this inhibited enzyme but these compounds do not readily cross the blood brain barrier (BBB) due to their permanent cationic charge and thus cannot efficiently reactivate cholinesterases in the central nervous system (CNS). In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun-inhibited human acetylcholinesterase (hAChE) has been evaluated. The dissociation constant KD of inhibited enzyme–oxime complex, the reactivity rate constant kr and the second order reactivation rate constant kr2 have been determined and have been compared to reference oximes HI-6, Obidoxime and 2-Pralidoxime (2-PAM). Regarding the reactivation of VX-inhibited hAChE, all compounds show a better reactivation potency than those of 2-PAM, nevertheless they are less efficient than obidoxime and HI-6. Moreover, one of seven described compounds presents an ability to reactivate tabun-inhibited hAChE equivalent to those of 2-PAM." @default.
• W2063062145 created "2016-06-24" @default.
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• W2063062145 date "2013-03-01" @default.
• W2063062145 modified "2023-10-18" @default.
• W2063062145 title "Syntheses and in vitro evaluations of uncharged reactivators for human acetylcholinesterase inhibited by organophosphorus nerve agents" @default.
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• W2063062145 doi "https://doi.org/10.1016/j.cbi.2012.09.023" @default.
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