Polarographic evidence for the interaction of reduced nitroimidazole derivatives with DNA bases

Abstract

Nitroimidazole drugs require reductive activation to exert antimicrobial and mutagenic activity (e.g. antiprotozoal, antitumour). The polarographic behaviour of several nitroimidazoles has been investigated in the presence and in the absence of the potential biological targets (i.e. adenine, guanine, cytosine and thymine). Adenine, guanine and cytosine caused the half-wave potential to shift in the positive direction. Thymine, however, caused negative shifts of the half-wave potentials. Adsorption is not the cause of the positive shifts observed but is clearly the cause of the negative shift induced by thymine. We conclude that primarily adenine and guanine are susceptible for interaction with reduced nitroimidazoles. The results also showed that the stability of the responsible intermediates is related to the value of the half-wave potential of the parent drug.