Synthesis, structure and antitumor activity of new benz[d,e]isoquinoline-1,3-diones

Arzneimittelforschung. 1995 Dec;45(12):1311-8.


New benz[d,e]isoquinoline-1,3-diones related to mitonafide (CAS 54824-17-8) and amonafide (CAS 69408-81-7) with double substitution on the chromophore and branched side chains have been synthesized and their biological activity determined. Molecular modeling studies of 3a based on X-ray crystallographic data of mitonafide have shown that the aromatic system intercalates between GC steps of DNA. The in vitro cytotoxic test data using CX-1 and LX-1 cells showed higher cytotoxic activities in disubstituted derivatives compared to both lead compounds. Some of the compounds have been selected for in vivo test using L1210 tumor cells and CX-1 cells. Two of them (3b and 3j) have shown promising activity as good candidates for clinical development.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Chemical Phenomena
  • Chemistry, Physical
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Imides / chemical synthesis*
  • Imides / chemistry
  • Imides / pharmacology*
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Leukemia L1210 / drug therapy
  • Mice
  • Mice, Inbred DBA
  • Models, Molecular
  • Molecular Conformation
  • Naphthalimides
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Imides
  • Isoquinolines
  • Naphthalimides
  • mitonafide
  • amonafide