7149-45-3Relevant academic research and scientific papers
HETEROAROMATIC ELECTROPHILES AND METHODS OF USING THEREOF
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Page/Page column 49; 50; 54, (2018/09/18)
Disclosed herein are compounds, compositions, and methods for reactivating or realkylating aged acetylcholinesterase inhibited by or conjugated to the organophosphorus compound. The organophosphorus compound can be a nerve agent. The acetylcholinesterase can be in the central nerve system (CNS) and/or the peripheral nervous system (PNS) of a subject. Accordingly, methods for ameliorating, diminishing, reversing, treating or preventing the toxic effects of an organophosphorus compound in a subject are provided herein. Methods for prophylactic or therapeutic treatment of exposure to an organophosphorus nerve agent are also provided.
Demonstration of in Vitro Resurrection of Aged Acetylcholinesterase after Exposure to Organophosphorus Chemical Nerve Agents
Zhuang, Qinggeng,Franjesevic, Andrew J.,Corrigan, Thomas S.,Coldren, William H.,Dicken, Rachel,Sillart, Sydney,Deyong, Ashley,Yoshino, Nathan,Smith, Justin,Fabry, Stephanie,Fitzpatrick, Keegan,Blanton, Travis G.,Joseph, Jojo,Yoder, Ryan J.,McElroy, Craig A.,Ekici, ?zlem Dogan,Callam, Christopher S.,Hadad, Christopher M.
supporting information, p. 7034 - 7042 (2018/06/13)
After the inhibition of acetylcholinesterase (AChE) by organophosphorus (OP) nerve agents, a dealkylation reaction of the phosphylated serine, referred to as aging, can occur. When aged, known reactivators of OP-inhibited AChE are no longer effective. Realkylation of aged AChE may provide a route to reversing aging. We designed and synthesized a library of quinone methide precursors (QMPs) as proposed realkylators of aged AChE. Our lead compound (C8) from an in vitro screen successfully resurrected 32.7 and 20.4% of the activity of methylphosphonate-aged and isopropyl phosphate-aged electric-eel AChE, respectively, after 4 days. C8 displays properties of both resurrection (recovery from the aged to the native state) and reactivation (recovery from the inhibited to the native state). Resurrection of methylphosphonate-aged AChE by C8 was significantly pH-dependent, recovering 21% of activity at 4 mM and pH 9 after only 1 day. C8 is also effective against isopropyl phosphate-aged human AChE.
