A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity.
Hexamethylmelamine (HMM) has previously been shown to be active against ovarian, breast and small cell lung cancer. However HMM dose not have aromatase-inhibitory activity. A newly developed HMM derivative, 2-N,N-dimethylamino-4, 6-bis (1-H-imidazol-1-yl)-1,3,5-triazine (SAE9), was found to have direct antitumor activity as well as aromatase-inhibitory activity. The direct antitumor activity on breast carcinoma cell lines (MCF-7, R-27 and MDA-MB-231) was assessed using the 3-(4,5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) on cells growing in monolayer culture. The 50% inhibitory concentrations (IC50) of SAE9 were found to be approximately 10(-4) M for each cell line, roughly equivalent to those of HMM. When the aromatase-inhibitory effect was assessed using a human placental aromatase-inhibitory assay, the IC50 of SAE9 was 5.5 x 10(-7) M, which was superior to that of aminoglutethimide (AG) (3.8 x 10(-5) M). In a rat uterine growth model treated with androstenedione as the in vivo aromatase inhibition assay, SAE9 had an effect equivalent to that of AG. Since SAE9 has both antitumor and aromatase-inhibitory activity on breast carcinoma cell lines with estrogen dependency, this and similar non-steroidal aromatase inhibitors are thought to be promising for further study.
Tanino
H
H
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Yamada
Y
Y
Koh
J I
JI
Takeuchi
T
T
Kase
S
S
Furukawa
T
T
Takahashi
M
M
Fukuda
S
S
Ogose
N
N
D006585:Altretamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014407:Tumor Cells, Cultured / Q000187:drug effects
D047072:Aromatase Inhibitors; D000616:Aminoglutethimide; C081888:2-N,N-dimethylamino-4,6-bis(1-H-imidazol-1-yl)-1,3,5-triazine; D006585:Altretamine