Satranidazole: mechanism of action on DNA and structure-activity correlations

Satranidazole (CG-10213-Go), a novel nitroimidazole possessing a C-N linkage at C2 of the imidazole ring has been examined, during reduction, for its ability to damage DNA. Physical damage to DNA was measured by viscometry, thermal denaturation and renaturation, and hydroxyapatite chromatography. Biologically relevant DNA damage was measured by a bacteriophage transfection assay. The drug produces extensive DNA damage characterized by helix destabilization and strand breakage. Its comparison with other 2- and 5-nitroimidazoles indicate it may be more active towards anaerobes than many 5-nitroimidazoles because its relatively high redox potential may make it more resistant to inactivation by oxygen.