We report a green chemistry approach for preparation of oxime-functionalized ILs as AChE reactivators: amide/ester linked IL, l-alanine, and l-phenylalanine derived salts bearing pyridinium aldoxime moiety. The reactivation capacities of the novel oximes were evaluated towards AChE inhibited by typical toxic organophosphates, sarin (GB), VX, and paraoxon (PON). The studied compounds are mostly non-toxic up to the highest concentrations screened (2 mM) towards Gram-negative and Gram-positive bacteria cell lines and both filamentous fungi and yeasts in the in vitro screening experiments as well as towards the eukaryotic cell (CHO-K1 cell line). Introduction of the oxime moiety in initially biodegradable structure decreases its ability to biodegradation. The compound 3d was shown to reveal remarkable activity against the AChE inhibited by VX, exceeding conventional reactivators 2-PAM and obidoxime. The regularities on antidotal activity, cell viability, plasma stability, biodegradability as well as molecular docking study of the newly synthesized oximes will be used for further improvement of their structures.

Biomedical Research Center University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic

Biomedical Research Center University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic; Department of Epidemiology Faculty of Military Health Sciences University of Defense Trebesska 1575 500 01 Hradec Kralove Czech Republic

Biomedical Research Center University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic; Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences University of Defense Trebesska 1575 500 01 Hradec Kralove Czech Republic

Department of Chemistry and Biotechnology Tallinn University of Technology Akadeemia Tee 15 12618 Tallinn Estonia

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

Department of Epidemiology Faculty of Military Health Sciences University of Defense Trebesska 1575 500 01 Hradec Kralove Czech Republic

Department of Organic and Bioorganic Chemistry Faculty of Pharmacy in Hradec Králové Charles University Heyrovského 1203 500 05 Hradec Kralove Czech Republic

Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro RJ Brazil

Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro RJ Brazil; Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 500 03 Hradec Kralove Czech Republic

School of Chemistry College of Science University of Lincoln Lincoln LN6 7TS UK

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