Antitumor agents. 1. 1,4-Bis[(aminoalkyl)amino]-9,10-anthracenediones

J Med Chem. 1979 Sep;22(9):1024-30. doi: 10.1021/jm00195a002.

Abstract

The condensation of alkylenediamines with quinizarin or with 2,3-dihydro-1,4,5,8-tetrahydroxy-9,10-anthracenedione, followed by oxidation, gave 1,4-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 1,4-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 greater than 433% increase in median life span (ILS) with 7/10 80-day survivors. Against P-388 leukemia, 40 gave greater than 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.

MeSH terms

  • Animals
  • Anthracenes / chemical synthesis*
  • Anthracenes / pharmacology
  • Anthracenes / therapeutic use
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Leukemia, Experimental / drug therapy
  • Mice
  • Neoplasms, Experimental / drug therapy
  • Structure-Activity Relationship

Substances

  • Anthracenes
  • Antineoplastic Agents