Interaction of nitroimidazole drugs with DNA in vitro: structure-activity relationships

An electrolytic reduction system has been developed to model the cytotoxic action of a range of nitroimidazole drugs against DNA hypoxic cells or anaerobic microorganisms. THe degree of damage induced by these drugs (measured as the release of [14C]-dT from DNA) and their relative rates of reduction have been correlated with their redox potentials. The results show that the correlation of drug-induced damage and electron affinity is related to the amount of drug reduced, and supports the hypothesis that at the molecular level the cytotoxic mechanism of reduced nitroimidazoles is identical in hypoxic mammalian cells, bacteria and protozoa.