6β,19-Bridged androstenedione analogs as aromatase inhibitors |
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Authors: | Sachiko Komatsu Ayaka Yaguchi Kouwa Yamashita Masao Nagaoka Mitsuteru Numazawa |
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Institution: | aTohoku Pharmaceutical University, 4-1 Komatsushima-4-chome, Aoba-ku, Sendai 981-8558, Japan;bNihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kita-adachi-gun, Saitama 362-0806, Japan |
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Abstract: | Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New 6β,19-bridged steroid analogs of androstenedione, 6β,19-epithio- and 6β,19-methano compounds 11 and 17, were synthesized starting from 19-hydroxyandrostenedione (6) and 19-formylandrost-5-ene-3β,17β-yl diacetate (12), respectively, as aromatase inhibitors. All of the compounds including known steroids 6β,19-epoxyandrostenedione (4) and 6β,19-cycloandrostenedione (5) tested were weak to poor competitive inhibitors of aromatase and, among them, 6β,19-epoxy steroid 4 provided only moderate inhibition (Ki: 2.2 μM). These results show that the 6β,19-bridged groups of the inhibitors interfere with binding in active site of aromatase. |
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Keywords: | Aromatase inhibitor 6β 19-Epithioandrostenedione 6β 19-Methanoandrostenedione 6β 19-Epoxyandrostenedione 6β 19-Cycloandrostenedione Human placental microsomes |
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