Effect of lipophilicity of nitroimidazoles on radiosensitization of hypoxic bacterial cells in vitro.

The effect of radiosensitization of hypoxic bacterial cells by 9 nitroimidazoles was measured in the bacterial strains E. coli AB 1157 and S. lactis 712. Seven of these compounds were similar to misonidazole in their redox properties, but differed widely in their lipophilicites. The dependence of sensitization enhancement on reduction potential was similar to that reported in mammalian cells. The efficiency of sensitization was similar for compounds of low lipophilicity, but increased if the octanol: water partition coefficients of the compounds were higher than about 3.5. With one compound, otherwise similar to misonidazole, the increased lipophilicity led to about one order of magnitude lower concentration achieving the same degree of radiosensitization.