Novel 5-aminoflavone derivatives as specific antitumor agents in breast cancer

J Med Chem. 1996 Aug 30;39(18):3461-9. doi: 10.1021/jm950938g.


In the course of our search for new antitumor agents in breast cancer, novel amino-substituted flavone derivatives were synthesized and examined for antitumor activities. Among them, 5,4'-diaminoflavone and some of its congeners showed remarkable antiproliferative activity against the estrogen receptor (ER)-positive and estrogen-responsive human breast cancer cell line MCF-7. The activity was observed irrespective of the presence or absence of estrogen. The 5-aminoflavone derivatives (5-AFs) are not classical anti-estrogens because they did not compete with [3H]estradiol to bind the estrogen receptor. Moreover, 5-AFs showed antitumor activity highly selective to the ER-positive breast cancer cell line, and they showed no effects against the ER-negative human cancer cell lines HeLa S3, WiDr, and MDA-MB-453. Although the mechanism of their selective antitumor activity to ER-positive breast cancer cells is unclear, 5-AFs are expected to be a new type of antitumor agents in breast cancer.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Estradiol / pharmacology
  • Female
  • Flavonoids / chemical synthesis*
  • Flavonoids / pharmacology
  • HeLa Cells
  • Humans
  • Receptors, Estrogen / analysis
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Flavonoids
  • Receptors, Estrogen
  • Estradiol