Pulse Radiolysis and Cellular Studies of a New Class of Radiosensitizers: 2-nitrobenzofurans

Summary

A group of 2-nitrobenzofurans possessing antibacterial and antiparasitic properties have now been shown to be potential radiosensitizers from investigations in simple aqueous solution by pulse radiolysis and from survival studies in yeast. The radical anions of several 2-nitrobenzofurans were formed by the rapid reaction of the parent molecules with hydrated electrons or with various pyrimidine electron adducts. Studies of equilibria between these radical anions, the parent nitrobenzofurans and the corresponding species derived from quinones with known one-electron reduction potentials, showed that the one-electron reduction potentials of all the furans under investigation lie between −285 and −309 mV. They are thus more electron affinic than the nitroimidazoles (misonidazole and metronidazole) currently under clinical evaluation. 5-Hydroxy- and 7-hydroxy-2-nitrobenzofuran were demonstrated to form weak complexes with DNA (binding constant 80 M⁻¹) and strong complexes with HSA (binding constant 10⁵ M⁻¹). In the yeast Saccharomyces cerevisiae the nitrobenzofurans exert radiosensitizing effects on survival either similar to or higher than misonidazole.