Monooxime-monocarbamoyl Bispyridinium Xylene-Linked Reactivators of Acetylcholinesterase-Synthesis, In vitro and Toxicity Evaluation, and Docking Studies

Acetylcholinesterase (AChE) reactivators are crucial antidotes to organophosphate intoxication. A new series of 26 monooxime-monocarbamoyl xylene linked bispyridinium compounds was prepared and tested in vitro along with known reactivators (pralidoxime, H16 obidoxime, trimedoxime, methoxime, K107, K108 and K203) on a model of tabun and paraoxon-, methlyparaoxon- and DFP inhibited human erythrocyte AChE. Although their ability to reactivate tabun inhibited AChE did not exceed that of the previously known compounds, some newly prepared compounds showed promising reactivation of pesticide inhibited AChE. The acute toxicity of the novel compounds was also determined. Docking studies using tabun-inhibited AChE were performed for three compounds of interest. The structure activity relationship (SAR) study confirmed the apparent influence of the xylene linkage and carbamoyl moiety on the reactivation ability and toxicity of the agents.