Assessment of a range of novel nitro-aromatic radiosensitizers and bioreductive drugs

In a directed search for the best compounds for clinical evaluation, some 150 selected nitroaromatic compounds, representing 6 distinct types, namely, furans, thiophenes, imidazoles, pyrazoles, pyrroles, and triazoles, have been synthesized and tested as hypoxic cell radiosensitisers and bioreductive drugs. These compounds have a wide range of one-electron redox potentials, ranging from −700 mV for 3-nitropyrroles to −250 mV for 5-nitrofurans. Within each series, those agents bearing alkylating moieties on the side chain are generally the more effective radiosensitisers in vitro . Studies in vivo demonstrated that the bifunctional nitroimidazoles were superior to the other nitroarenes tested. In terms of bioreductive cell killing, the best differential between oxic and hypoxic cell toxicity was shown for the bifunctional 2-nitroimidazoles, which had values greater than 20. In contrast, the other classes of nitroarines generally showed differential toxicities of less than 10.