We have synthesized the (19R)- and (19S)-isomers (2 and 3 respectively) of 10 beta-oxiranylestr-4-ene-3,17-dione. The configurations and conformations of these compounds were established by X-ray crystallographic analysis. Each of these compounds is a powerful competitive inhibitor of human placental microsomal aromatase, and stereoselectivity of inhibition was observed (Ki values for 2 and 3 were 7 and 75 nanomolar, respectively). Spectroscopic studies with purified aromatase indicate that the inhibition process involves reversible binding of oxirane oxygen to the heme iron of the enzyme. The (19R)- and (19S)-10 beta-thiiranes (6 and 7) corresponding to 2 and 3 have been synthesized from the oxiranes by a stereospecific process. The thiiranes are very effective competitive inhibitors of placental aromatase, and show even greater stereoselectivity in binding than the oxiranes (Ki values for 6 and 7 were 1 and 75 nanomolar, respectively). Spectroscopic studies with purified aromatase indicate that the inhibition process involves reversible binding of thiirane sulfur to heme iron.

Aromatase Inhibitors↗

PubMedDate not supplied

Cancer prevention education in a hospice program. Counseling during bereavement: how effective is it?

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Adult↗

PubMedDate not supplied

Effects of novel acetylenic and allenic steroids on the rat prostate.

Novel acetylenic and allenic steroid analogs previously have been synthesized in this laboratory and were shown to be potent irreversible inhibitors of delta5-3-ketosteroid isomerase from P. Testosteroni. This bacterial enzyme catalyzes the conversion of delta5-3-ketosteroids to the corresponding delta4-3-ketosteroids. These isomerizations are key steps in the mammalian biosynthesis of steroid hormones, and it was hoped that the acetylenic and allenic steroid analogs migh inhibit androgen biosynthesis. We have now shown that these compounds cause a significant and dose-dependent decrease in the wet weight of both ventral and dorsal lateral prostate in the mature male rat.

Alkenes↗