Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates.

نویسندگان

  • Francine S Katz
  • Stevan Pecic
  • Timothy H Tran
  • Ilya Trakht
  • Laura Schneider
  • Zhengxiang Zhu
  • Long Ton-That
  • Michal Luzac
  • Viktor Zlatanic
  • Shivani Damera
  • Joanne Macdonald
  • Donald W Landry
  • Liang Tong
  • Milan N Stojanovic
چکیده

Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups--Mannich phenols and general bases--that are capable of reactivating OPC--inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data, significantly broaden the available approaches for reactivation of AChE.

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Docking Studies, Synthesis, and In-vitro Evaluation of Novel Oximes Based on Nitrones as Reactivators of Inhibited Acetylcholinesterase

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Docking Studies, Synthesis, and In-vitro Evaluation of Novel Oximes Based on Nitrones as Reactivators of Inhibited Acetylcholinesterase

Acetylcholinesterase has important role in synaptic cleft. It breaks down the acetylcholineatcholinergic synapsesand terminates the cholinergic effects. Some chemical agents likeorganophosphorus compounds (OPCs) including nerve agents and pesticides react withacetylcholinesteraseirreversibly. They inhibit normal biological enzyme action and resultin accumulation of acetylcholineand show toxic e...

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عنوان ژورنال:
  • Chembiochem : a European journal of chemical biology

دوره 16 15  شماره 

صفحات  -

تاریخ انتشار 2015