Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide

J Med Chem. 1987 Apr;30(4):664-9. doi: 10.1021/jm00387a014.


The synthesis, physicochemical properties, and antitumor activity of a series of N-[2-(dialkylamino)alkyl]-acridine-4-carboxamides are reported. The compounds bind to DNA by intercalation, but exist under physiological conditions as monocations due to the weakly basic acridine chromophore (pKa = 3.5-4.5). The acridine-4-carboxamides show very broad structure-activity relationships (SAR) for antileukemic activity, with substituents at nearly all acridine positions proving acceptable. The compounds also show remarkable activity against the Lewis lung solid tumor in vivo, with several analogues capable of effecting 100% cures of the advanced disease. The broad SAR and high solid-tumor activity of the 9-acridine-4-carboxamides imply they should be considered as a completely new class of antitumor agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoacridines / chemical synthesis
  • Aminoacridines / metabolism
  • Aminoacridines / therapeutic use*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / drug therapy*
  • Chemical Phenomena
  • Chemistry
  • DNA / metabolism
  • Intercalating Agents / chemical synthesis
  • Intercalating Agents / metabolism
  • Intercalating Agents / therapeutic use*
  • Leukemia P388 / drug therapy*
  • Leukemia, Experimental / drug therapy*
  • Lung Neoplasms / drug therapy*
  • Mice
  • Structure-Activity Relationship


  • Aminoacridines
  • Antineoplastic Agents
  • Intercalating Agents
  • DNA