Evaluation of 2-Amino-5-Nitrothiazole as a Hypoxic Cell Radiosensitizer

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Abstract
The nitroheterocyclic compound 2-amino-5-nitrothiazole (ANT) was evaluated as a hypoxic radiosensitizer. Experiments with bacteria showed that this agent was similar to misonidazole in radiosensitizing activity, but was less cytotoxic and less mutagenic than misonidazole. Experiments with EMT6 [mouse mammary] tumor cells in culture showed ANT to be an effective hypoxic radiosensitizer, although slightly less active than misonidazole, and to be less cytotoxic than misonidazole. ANT was more toxic to mice than misonidazole and produced a spectrum of symptoms, including hyperactivity and agitation, different from those of misonidazole. The toxicities of ANT and misonidazole were additive. The maximum levels of ANT achievable in the tumors after i.p. injection of nontoxic doses of drug were low (< 3 .times. 10-4 M); the radiosensitization obtainable with the drug in vivo was inferior to that obtainable with misonidazole. Nitrothiazoles might be an interesting class of nitroheterocyclic radiosensitizers [for cancer radiotherapy], but molecules with increased solubility and improved pharmacokinetics would be necessary for efficacy in vivo.