Treatment of mouse tumors with 7-con-O-methylnogarol and other analogs of the anthracycline antibiotic, nogalamycin.

Abstract

The chemotherapeutic activity of analogs of the anthracycline antibiotic, nogalamycin, was investigated in the P388 and L1210 leukemias and the B16 melanoma in mice. Among the compounds tested, 7-con-O-methylnogarol was found to have superior activity. Depending on the route and schedule of administration, increases in lifespan (ILS) in excess of 100% were observed in all three tumor systems. Additional testing of 7-con-O-methylnogarol demonstrated significant activity in the murine colon 26 and colon 38 tumors and the CD8F1 mammary tumor. 7-Con-O-methylnogarol was not significantly effective against murine Lewis lung carcinoma, although ILSs of 38% and 29% were achieved in two experiments. Activity was observed against ip inoculated P388 leukemia after ip, sc, oral, and iv drug administration. 7-Con-O-methylnogarol was also highly active (ILS greater than or equal to 120%) after ip drug administration to mice with iv inoculated P388 leukemia. Significant ILS values resulted from a variety of schedules of administration against ip inoculated P388 leukemia and B16 melanoma. Experiments in which the time of single-dose administration was varied prior to the time of ip P388 leukemia inoculation showed that residual drug or bioactive drug-related materials remained in mice for 8 hours after 50 mg/kg administered ip and for 48 hours after 200 mg/kg administered sc.