Comparative Toxicity of Bis-pyridinium Acetamide Derivatives in Human Cell Lines and their Acute Toxicity in Swiss Albino Mice

Abstract

Having established the antidotal efficacy of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide (HNK oximes) against Diisopropylphosphorofluoridate (DFP) and sarin poisoning. Toxicity of HNK series and 2-PAM oximes on Human cell lines and Swiss male mice i.e. in vitro and in vivo to reported. Toxicity of the oximes was investigated in Hela, Hep G2 and HEK 293 cell lines and compared with most commonly used 2-PAM. Median lethal doses (LD50) of the oximes (2-PAM, HNK-102, HNK-106, and HNK-111) were also determined following intramuscular, intraperitoneal, intravenous and oral routes of administration. All tested oximes showed no cytotoxic effect on all three cell lines in concentrations up to 0.05 mg/mL. At higher dose (0.5 mg/mL), HNK-102 found to be less toxic thus safer than 2-PAM and other oximes in all the three cell lines. In corroboration with in vitro finding, HNK-102 was found to be least toxic compared to other oximes via intra-peritoneal and intravenous routes of administration. Also, HNK-102 was found to be unequivocally safer compared to that of 2-PAM through i.m. and i.p. routes. For all tested oximes, toxicity following oral route, was found to be lower compared to injections, signifying that these are safer and convenient compounds for administration. These finding also suggested that HNK-102 is safer and better lead as an antidote compared to 2-PAM, against OP intoxicants.