ANTITUMOR IMIDAZOTETRAZINES .6. EXPERIMENTAL ANTITUMOR-ACTIVITY AGAINST MURINE TUMOR-MODEL SYSTEMS OF 8-CARBAMOYL-3-(2-CHLOROETHYL)IMIDAZO[5,1-D]-1,2,3,5-TETRAZIN-4(3H)-ONE(MITOZOLOMIDE), A NOVEL BROAD-SPECTRUM AGENT

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (7) , 3008-3013
Abstract
8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L1210 and P388 leukemias irrespective of the route of tumor and/or drug administration; in these tests, animals receiving 105 cells i.p. survived > 60 days after treatment. Potent effects were also observed against the TLX5 lymphoma (s.c.) and B16 melanoma (i.p.). In other experiments, 7 of 10 animals implanted with 2 .times. 105 Lewis lung carcinoma cells survived > 60 days while 10 of 10 animals survived > 60 days after implantation of the Colon 26 tumor. Potent inhibition of the solid tumor models was also observed with complete cures of the Colon 38, M5076 sarcoma and ADJ/PC6A plasmacytoma. In cross-resistance studies, the compound was ineffective against an L1210 leukemia made resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea and against a TLX5 lymphoma resistant to dimethyltriazenes but cured animals bearing the L1210 leukemia with derived resistance to cyclophosphamide.

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