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

International Journal of Molecular Sciences

Vendula Sepsova¹  Jana Zdarova Karasova³  Jan Korabecny¹  Rafael Dolezal⁴  Filip Zemek¹  Brian J. Bennion² 

[1]Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

[2] E-Mails:

[3]Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, 7000 East Ave, Livermore, CA 94550, USA

[4] E-Mail:

[5]Department of Public Health, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

[6] E-Mail:

[7]University Hospital, Biomedicinal Research Centre, Sokolska 581, 50005 Hradec Kralove, Czech Republic

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关键词: oximes;    acetylcholinesterase;    inhibitors;    SAR study;   

DOI  :  10.3390/ijms140816882

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland