Light-switchable diazocines as potential inhibitors of testosterone-synthesizing 17β-hydroxysteroid dehydrogenase 3.

In patients with prostate carcinoma as well as in some other cancer types, the reduction of testosterone levels is desired because the hormone stimulates cancer cell growth. One molecular target for this goal is the inhibition of 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3), which produces testosterone from its direct precursor androstenedione. Recent research in this field is trying to harness photopharmacological properties of certain compounds so that the inhibitory effect could be turned on and off by irradiation.

Reduction of photoswitched, nitrogen bridged N-acetyl diazocines limits inhibition of 17βHSD3 activity in transfected human embryonic kidney 293 cells.

Testosterone depletion is a common aim in the treatment of hormone-dependent prostate cancer, since the steroid boosts the tumor's proliferation. Therefore, inhibition of 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3), which catalyzes the carbonyl reduction of androstenedione to testosterone, represents an expedient therapeutic drug target. Among the compounds targeting 17βHSD3, tetrahydrodibenzazocines have been reported to be highly potent inhibitors.

Chrysin and silibinin sensitize human glioblastoma cells for arsenic trioxide.

Arsenic trioxide (ATO) is highly efficient in treating acute promyelocytic leukemia. Other malignancies, however, are often less sensitive. Searching for compounds sensitizing arsenic resistant tumours for ATO the plant polyphenols, chrysin and silibinin, and the ATP binding cassette (ABC) transporter inhibitor MK-571, respectively, were investigated in human glioblastoma A-172 cells.