ANTI-TUMOR AGENTS .1. 1,4-BIS[(AMINOALKYL)AMINO]-9,10-ANTHRACENEDIONES

The condensation of alkylenediamines with quinizarin or with 2, 3-dihydro-1, 4, 5, 8-tetrahydroxy-9, 10-anthracenedione, followed by oxidation, gave l, 4-bis[(aminoalkyl)amino]-9, 10-anthracenediones. Some of these compounds and their 2, 3-dihydro derivatives were markedly active against both leukemias and solid tumors in mice. Activity was maximal with 5, 8-dihydroxylation and l, 4-bis[(2-aminoethyl)amino] substitution, in which the terminal nitrogen atoms were either unsubstituted (compound 50) or carried 2-hydroxyethyl groups (compound 40), indicating the importance of hydrophilicity. Against B-16 melanoma, 50 gave > 433% increase in median life span (ILS) with 7/10 80-day survivors. Against P-388 leukemia, 40 gave > 500% ILS with 4/5 60-day survivors; its efficacy and therapeutic index equaled or surpassed those of adriamycin, cyclophosphamide, daunorubicin, methotrexate, or 5-fluorouracil. Against L-1210 leukemia, B-16 melanoma, and colon tumor 26, 40 was generally as effective or more effective than adriamycin and is now undergoing preclinical toxicological evaluation. © 1979, American Chemical Society. All rights reserved.