Potential radiosensitizing agents. 4. 2-Nitroimidazole nucleosides.
A series of 2-nitroimidazole nucleoside analogues has been synthesized as potential radiosensitizers in an effort to reduce neurotoxicity and increase therapeutic efficacy. The 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl and glucothiopyranosyl analogues of 2-nitroimidazole were synthesized by condensation in the presence of stannic chloride and mercuric cyanide. The deacetylation of these esters was carried out with sodium methoxide at 0 degree C. Condensation of the trimethylsilyl derivative of 2-nitroimidazole with methyl 2-deoxy-2-chloro-4,7,8,9-tetra-O-acetyl-N-acetyl-alpha-D-neuraminate was achieved in the presence of mercuric bromide. These agents were tested for cytotoxicity and radiosensitization in vitro against Chinese hamster (V-79) cells under oxic and hypoxic conditions. The thioglucose and sialic acid analogues were found to be active radiosensitizers.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D003412:Cricetulus; D005720:Gamma Rays; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents