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Int. J. Mol. Sci. 2013, 14(8), 16882-16900; doi:10.3390/ijms140816882
Article

Oximes: Inhibitors of Human Recombinant Acetylcholinesterase. A Structure-Activity Relationship (SAR) Study

1,†
,
2,3
,
1,3,†
,
3,†
,
1
,
4,†
 and
3,5,*
1 Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic 2 Department of Public Health, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic 3 University Hospital, Biomedicinal Research Centre, Sokolska 581, 50005 Hradec Kralove, Czech Republic 4 Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, 7000 East Ave, Livermore, CA 94550, USA 5 Center of Advances Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 8 May 2013 / Revised: 1 August 2013 / Accepted: 2 August 2013 / Published: 16 August 2013
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Abstract

Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. However, oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. The goal of the present study is to determine how oxime structure influences the inhibition of human recombinant AChE (hrAChE). Therefore, 24 structurally different oximes were tested and the results compared to the previous eel AChE (EeAChE) experiments. Structural factors that were tested included the number of pyridinium rings, the length and structural features of the linker, and the number and position of the oxime group on the pyridinium ring.
Keywords: oximes; acetylcholinesterase; inhibitors; SAR study oximes; acetylcholinesterase; inhibitors; SAR study
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Sepsova, V.; Karasova, J.Z.; Korabecny, J.; Dolezal, R.; Zemek, F.; Bennion, B.J.; Kuca, K. Oximes: Inhibitors of Human Recombinant Acetylcholinesterase. A Structure-Activity Relationship (SAR) Study. Int. J. Mol. Sci. 2013, 14, 16882-16900.

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