Evaluation of novel radiation sensitizers in vitro and in vivo.
In principle, radiation sensitizers with therapeutic ratios greater than that of misonidazole can be obtained either by increasing sensitizing efficiency, decreasing toxicity or preferably both. This paper illustrates, firstly that a 5-nitroimidazole (S73-0662) with an electron affinity close to that of metronidazole shows sensitizing efficiency similar to misonidazole both in vitro and in vivo. The suggestion is made that this compound should receive a detailed toxicological study to ascertain if its toxicity is lower than misonidazole. Secondly, Imuran, a 5-substituted 4-nitroimidazole and one of a series of compounds which show sensitizing efficiencies in vitro much greater than would be predicted from electron affinity considerations, also shows good sensitization in vivo. Compounds in this series are generally metabolically unstable and the positive results with Imuran in vivo provide a direction for future synthesis of novel sensitizers.
D000818:Animals; D001379:Azathioprine / Q000494:pharmacology; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D003412:Cricetulus; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D004583:Electrons; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology; D010084:Oxidation-Reduction; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D001379:Azathioprine