title: KIH-802: 2-nitroimidazole-1-acetohydroxamate as a hypoxic cell radiosensitizer.
abstract: We have identified potassium 2-nitroimidazole-1-acetohydroxamate (KIH-802) as a hypoxic cell radiosensitizer potentially superior to Miso. The water-soluble acetohydroxamates of 2-nitroimidazole (KIH-802; free acid 801) and 4-nitroimidazole (KIH-852) were designed, synthesized, and evaluated by in vitro and in vivo screening against EMT6 cells. Enhancement ratios of KIH-802 and 801 were 1.92 and 1.68, respectively, compared with 1.58 for MISO all at 1 mM. These acetohydroxamates are also expected to be more effective in vitro than SR-2508 based on our previous experiments. In vivo ERs of KIH-802, 801, and 852 were 1.75, 1.50, and 1.35, respectively, compared with 1.57 for MISO all at the same dose of 200 mg/kg. The data clearly show that the addition of an acetohydroxamic acid moiety to the 2-nitroimidazole skeleton can enhance radiosensitizing ability.
authors.affiliation: Pharmaceutical Institute, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hori
authors.forename: C
authors.initials: C
authors.lastname: Murayama
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Shibamoto
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Onoyama
authors.forename: S
authors.initials: S
authors.lastname: Inayama
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects
chemical_list: D006877:Hydroxamic Acids; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C057685:2-nitroimidazole-1-acetohydroxamic acid; D010100:Oxygen