title: Stable reduction product of misonidazole.
abstract: The predominant stable product (greater than 80%) of the anaerobic radiation chemical reduction (pH 7, formate, N2O) of misonidazole (MISO) has been identified as the cyclic guanidinium ion MISO-DDI, a 4,5-dihydro-4,5-dihydroxyimidazolium ion. This cation was prepared as its sulfate salt by the reaction of glyoxal and the appropriate N-substituted guanidinium sulfate. Its formation during MISO reduction was established by NMR spectral comparison and by derivatization as glyoxal bis-oxime, which was formed in 86% yield in fully reduced systems. The toxicity of pure MISO-DDI X sulfate was examined in vivo (C3H mice) and in vitro (CHO cells). This product is less toxic than the parent MISO and free glyoxal. A reactive, short-lived, intermediate is suggested as the agent responsible for the toxicity of MISO under hypoxic conditions.
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000031:analogs & derivatives / Q000528:radiation effects / Q000633:toxicity; D010084:Oxidation-Reduction; D011854:Radiochemistry
chemical_list: C049949:2-amino-4,5-dihydro-4,5-dihydroxy-1-(2'-hydroxy-3'-methoxy-1'-propyl)imidazole; D008920:Misonidazole