title: Oximes: inhibitors of human recombinant acetylcholinesterase. A structure-activity relationship (SAR) study.
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.
authors: Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001 Hradec Kralove, Czech Republic.
authors: Vendula
authors: V
authors: Sepsova
authors: Jana Zdarova
authors: JZ
authors: Karasova
authors: Jan
authors: J
authors: Korabecny
authors: Rafael
authors: R
authors: Dolezal
authors: Filip
authors: F
authors: Zemek
authors: Brian J
authors: BJ
authors: Bennion
authors: Kamil
authors: K
authors: Kuca
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D010091:Oximes / Q000737:chemistry*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D010091:Oximes; D000110:Acetylcholinesterase
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