The synthesis and in vitro testing of symmetric bisquaternary salts with pyridin-isonitrosoacetanilide structure, active in the exposure to neurotoxic chemical agents

Neurotoxic chemical agents induce complex toxicological effects with major adverse effects for those who are exposed to them. Medical countermeasures include administering atropine, a cholinesterase reactivating oxime and an anticonvulsant. The purpose of this reseach is the optimization of an antidote-based treatment in the intoxication with organophosphates through the synthesis and toxicological testing of new compounds with a pyridin-isonitrosoacetanilide structure and their comparison with obidoxime as reference. The objective of this study was the in vitro/in vivo assessment of the antidote properties and acute toxicity of synthethic oximes active in the exposure to neuroparalytic organophosphates. The CT50 value for obidoxime was estimated, through calculus, to be 3.24 mg/ml and 9.33 ×10 -6 M respectively. The CT50 value for Bis1,3[2-hydroxyimino-N-(pyridyl)acetamide]oxapropandichloride (HIN 2) was estimated to be 2.72 mg/ml and 6.29 ×10 -6 M respectively. The studied compounds showed values close to cellular viability at low and moderate equimolecular concentrations, administered in vitro to a cellular culture of fibroblasts. Bis1,3[2-hydroxyimino-N-(piridyl)acetamide]oxapropandichloride (HIN 2) showed an in vitro cellular viability value smalled than obidoxime at higher equimolecular concentrations, proving itself to be more toxic than obidoxime at high concentrations. Taking into account the close values of CT50, the newly synthethized compound, having this particular characterization from a toxicological standpoint, qualifies for further studies as an antidote.