Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are therefore highly toxic compounds. For the recovery of inhibited AChE, antidotes from the group of pyridinium or bispyridinium aldoxime reactivators (pralidoxime, obidoxime, HI-6) are used in combination with anticholinergics and anticonvulsives. Therapeutic efficacy of reactivators (called “oximes”) depends on their chemical structure and also the type of organophosphorus inhibitor. Three novel oximes (K131, K142, K153) with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens) AChE (HssACHE) and BChE (HssBChE) inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate). According to the obtained results, none of the prepared oximes were able to satisfactorily reactivate paraoxon-inhibited cholinesterases. On the contrary, extraordinary activity of obidoxime in the case of paraoxon-inhibited HssAChE reactivation was confirmed. Additional docking studies pointed to possible explanations for these results.

Biomedical Research Center University Hospital Hradec Kralove Sokolska 581 50005 Hradec Kralove Czech Republic

Center for Basic and Applied Research Faculty of Informatics and Management University of Hradec Kralove 50003 Hradec Králové Czech Republic

College of Life Science Yangtze University Jingzhou Hubei 434025 China

Faculty of Chemical and Food Technology Slovak University of Technology 81237 Bratislava Slovakia

Faculty of Military Health Sciences University of Defence Trebesska 1575 50001 Hradec Kralove Czech Republic

Faculty of Science Department of Chemistry University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralove Czech Republic

Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense Military Institute of Engineering Praça General Tiburcio 80 Urca 22290 270 Rio de Janeiro RJ Brazil

Laboratory of Molecular Modeling Chemistry Department Federal University of Lavras 37200 000 Lavras MG Brazil

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