Novel silylated steroids as aromatase inhibitors.
Androst-4-en-3-one analogs incorporating a trimethylsilyl or a trimethylsilylmethyl group at C-1, C-2 or C-19 were prepared and evaluated as inhibitors of aromatase. Only 10-[1-hydroxy-2-(trimethylsilyl)ethyl]estr-4-ene-3,17-dione inhibited human placental aromatase. Enzyme kinetic analysis revealed competitive inhibition [apparent dissociation constant (Ki) of 562 +/- 12 nM] associated with marginal time-dependent inhibition.
D000737:Androstenols / Q000138:chemical synthesis* / Q000494:pharmacology; D047072:Aromatase Inhibitors; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D012825:Silicon / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000737:Androstenols; D047072:Aromatase Inhibitors; D007202:Indicators and Reagents; D014297:Trimethylsilyl Compounds; D012825:Silicon