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.
Akama
T
T
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Company, Ltd., Shizuoka-ken, Japan.
Shida
Y
Y
Sugaya
T
T
Ishida
H
H
Gomi
K
K
Kasai
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005419:Flavonoids; D011960:Receptors, Estrogen; D004958:Estradiol