The development of
acetylcholinesterase reactivators, i.e., antidotes against
organophosphorus poisoning, is an important goal of defense research. The aim of this study was to compare cytotoxicity and chemical structure of five currently available
oximes (
pralidoxime,
trimedoxime,
obidoxime,
methoxime, and asoxime) together with four perspective
oximes from K-series (K027, K074, K075, and K203). The cytotoxicity of tested substances was measured using two methods - colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
bromide assay and impedance based real-time cytotoxicity assay - in three different cell lines (HepG2, ACHN, and NHLF). Toxicity was subsequently expressed as toxicological index IC50. The tested compounds showed different cytotoxicity ranging from 0.92 to 40.06 mM. In HepG2 cells, K027 was the least and asoxime was the most toxic reactivator. In ACHN and NHLF cell lines,
trimedoxime was the compound with the lowest adverse effects, whereas the highest toxicity was found in
methoxime-treated cells. The results show that at least five structural features affect the reactivators' toxicity such as the number of
oxime groups in the molecule, their position on pyridinium ring, the length of
carbon linker, and the
oxygen substitution or insertion of the double bond into the connection chain. Newly synthetized
oximes with IC50 ≥ 1 mM evaluated in this three cell lines model might appear suitable for further testing.