ACTIVITY OF A NOVEL ANTHRACENYL BISHYDRAZONE, 9,10-ANTHRACENEDICARBOXALDEHYDE BIS[4,5-DIHYDRO-1H-IMIDAZOL-2-YL)HYDRAZONE] DIHYDROCHLORIDE, AGAINST EXPERIMENTAL-TUMORS IN MICE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (2) , 440-444
Abstract
9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride (CL 216942; bisantrene hydrochloride; NSC 337766), a member of a new chemical class of compounds with antineoplastic properties, was evaluated for antitumor activity in experimental murine tumor systems. The compound produced significant increases in life span (ILS) and long-term survivors among mice bearing transplantable leukemias and solid tumors. Optimal treatment regimens resulted in an ILS of > 173 and 151% in mice with P388 and L1210 leukemia, respectively, an ILS of > 85% in mice with Lieberman plasma cell tumor, and an ILS of > 200, 150, and 63%, respectively, in mice with B16 melanoma, colon tumor 26 and Ridgway osteogenic sarcoma. An adriamycin-resistant subline of P388 leukemia showed complete cross-resistance to CL 216942. The compound was active when administered by the i.p., i.v., and s.c. routes, but p.o. [per os] activity was not observed. Significant schedule dependency was not observed when the drug was administered once daily for 9 days, once every 4 days, or as a single dose, but single doses typically produced the best effects. CL 216942 was a potent inhibitor of DNA and RNA synthesis in L5178Y lymphoma cells cultured in vitro, and preliminary studies indicated the drug was a DNA-intercalating agent. The drug was cytotoxic for rapidly proliferating and nonproliferating (Go) human colon carcinoma WiDR cells in vitro.