Androst-5-Ene-7,17-dione: A novel class of suicide substrate of aromatase

• Published in: Biochemical and biophysical research communications Vol. 186; no. 1; pp. 32 - 39
• Main Authors: Numazawa, Mitsuteru, Mutsumi, Ayako, Hoshi, Kumiko, Tanaka, Yuko
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.07.1992; Elsevier
• Subjects: Analytical, structural and metabolic biochemistry; Androstenedione - analogs & derivatives; Androstenedione - chemical synthesis; Androstenedione - metabolism; Androstenedione - pharmacology; Aromatase - metabolism; Aromatase Inhibitors; Binding, Competitive; Biological and medical sciences; Enzymes and enzyme inhibitors; Female; Fundamental and applied biological sciences. Psychology; Humans; Indicators and Reagents; Kinetics; Magnetic Resonance Spectroscopy; Microsomes - enzymology; Molecular Structure; Oxidoreductases; Placenta - enzymology; Pregnancy; Substrate Specificity; Characterization; Human; Steroid; Placenta; Enzyme; Enzyme inhibitor; Substrate inhibition; Oestrogen synthase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(05)80771-5

5-En-7-one steroid 1 was found to be a potent inhibitor of aromatase. This along with its 19-hydroxy derivative 7 was characterized as suicide substrate of human placental aromatase (k inact 's of 0.069 and 0.058 min −1 and K i's of 143 nM and 11.1 μM, respectively, or steroids 1 and 7). The results suggest that the 19-oxygenation would be involved in the irreversible inactivation of aromatase by the 5-en-7-one steroids.