A NEWLY DEVELOPED HEXAMETHYLMELAMINE DERIVATIVE, SAE9 WITH BOTH ANTITUMOR AND AROMATASE-INHIBITORY ACTIVITY

Hexamethylmelamine (HMM) has previously been shown to be active agains t ovarian, breast and small cell lung cancer. However HMM dose not hav e 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-inhi bitory activity. The direct antitumor activity on breast carcinoma cel l lines (MCF-7, R-27 and MDA-MB-231) was assessed using the 3-(4,5-dim ethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) on cells gro wing in monolayer culture. The 50% inhibitory concentrations (IC50) of SAE9 were found to be approximately 10(-4) M for each cell line, roug hly equivalent to those of HMM. When the aromatase-inhibitory effect w as assessed using a human placental aromatase-inhibitory assay, the IC 50 of SAE9 was 5.5 X 10(-7) M, which was superior to that of aminoglut ethimide (A G) (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 inhibito rs are thought to be promising for further study.