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

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.