Analogues of RSU-1069: radiosensitization and toxicity in vitro and in vivo
A series of nitroimidazoles containing aziridine and alkyl-substituted aziridine functions has been synthesized. The 2-nitroimidazole compounds examined all show greater radiosensitizing efficiency in vitro than misonidazole. The 4- and 5-nitroimidazole analogues are also more efficient than equivalent compounds which do not contain the alkylating aziridine moiety. All the compounds show increased toxicity towards hypoxic cells relative to aerobic cells, but this toxicity is reduced by alkyl-substitution of the aziridine ring. In vivo toxicity can also be reduced by modification of the aziridine function, but such alterations appear to have less effect upon the high radiosensitizing efficiency of these compounds in vivo. As a consequence of this study, compounds of potentially improved therapeutic utility compared to RSU-1069, the first reported member of this class, have been identified.
- Research Organization:
- Medical Research Council, Oxon, England
- OSTI ID:
- 5004550
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 7; ISSN IOBPD
- Country of Publication:
- United States
- Language:
- English
Similar Records
Radiosensitizing and toxic effects of RSU-1069 on hypoxic cells in a murine tumor
RSU 1069, a 2-nitroimidazole containing an alkylating group: high efficiency as a radio- and chemosensitizer in vitro and in vivo
Related Subjects
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
DRUGS
HAMSTERS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IN VITRO
MAMMALS
MICE
MISONIDAZOLE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
RODENTS
TOXICITY
VERTEBRATES