Mutagenicity and toxicity of carcinogenic and other hydrazine derivatives: correlation between toxic potency in animals and toxic potency in Salmonella typhimurium TA1538

Abstract

Eleven hydrazine derivatives and an aromatic amine were examined for mutagenicity and toxicity to Salmonella typhimurium. Phenylhydrazine, 2-nitrophenylhydrazine, 4-nitrophenylhydrazine, 2,4-dinitrophenylhydrazine, p-tolylhydrazine, and 4-nitroaniline were found to be frameshift mutagens (strain TA1538). Benzylhydrazine, m-hydroxybenzylhydrazine, p-hydrazinobenzoic acid, L-tyrosine hydrazide, p-aminobenzoyl hydrazide, and isoniazid were not mutagenic. All chemicals were toxic to strain TA1538. A qualitative correlation was found between the pK of the compounds and their mutagenicity. Relative toxicities of hydrazines to bacteria were found to be closely correlated with the relative toxicities of the same compounds in animals. Described herein is a methodology for the rapid prescreening of chemicals which may be used as drugs for those with a high benefit/risk ratio.

Synthesis and Miscoding Specificity of Oligodeoxynucleotide Containing 8-Phenyl-2‘-deoxyguanosine

“…Methyl radicals and methyldiazonium ions are thought to play a role in mutagenesis and carcinogenesis. Phenylhydrazine, used as a hemolytic agent (), and phenylhydrazine analogues are known to be mutagenic in bacteria ( − ). Based on studies of 8-MedG, aryl radicals and arenediazonium ions are suspected to be involved in the formation of DNA adducts that may lead to mutation.…”

Heparin‐induced circular dichroism of an achiral, bicyclic species

“…Under identical conditions as those used for QD and rac ‐chloroquine, no heparin‐induced CD was observed for HZQ and dramatically reduced heparin/solute association (∼110 M −1 at pH 6.0) was obtained. The relatively low association is likely a function of the HZQs reduced ionization at pH 6.0 (p K a2 ∼5.224) relative to QD and chloroquine (p K a2 ∼8.425). As such, these results appear to support the importance of the solute alkylamino side chain and ionization in the solute–GAG interactions.…”

Discovery of new ATP-competitive inhibitors of human DNA topoisomerase IIα through screening of bacterial topoisomerase inhibitors

“…While this structural modification decreased the ontarget activity by approximately ten-fold, 19 obtained a cytotoxic activity. This could, however, be associated to the well-known general toxicity of hydrazine derivatives [40].…”