Structure-cytotoxicity relationships of nitroimidazoles in an in vitro system

Correlations of cytotoxicity of nitroimidazoles and their electron affinity depend upon the degree of reduction of the drugs. If the end-point chosen to assess cytotoxicity is one at which incomplete reduction has occurred the slope of the correlation is positive, with respect to E71, but if measurements are taken after complete reduction of the drugs the slope is a negative one. The production of nitrite ion by 5-nitroimidazoles depends on the base composition of DNA suggesting that the active agent responsible for cytotoxicity is the one-electron radical anion, R--NO2-.