6beta,19-Bridged androstenedione analogs as aromatase inhibitors.
Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New 6beta,19-bridged steroid analogs of androstenedione, 6beta,19-epithio- and 6beta,19-methano compounds 11 and 17, were synthesized starting from 19-hydroxyandrostenedione (6) and 19-formylandrost-5-ene-3beta,17beta-yl diacetate (12), respectively, as aromatase inhibitors. All of the compounds including known steroids 6beta,19-epoxyandrostenedione (4) and 6beta,19-cycloandrostenedione (5) tested were weak to poor competitive inhibitors of aromatase and, among them, 6beta,19-epoxy steroid 4 provided only moderate inhibition (K(i): 2.2 microM). These results show that the 6beta,19-bridged groups of the inhibitors interfere with binding in active site of aromatase.
Komatsu
Sachiko
S
Tohoku Pharmaceutical University, 4-1 Komatsushima-4-chome, Aoba-ku, Sendai 981-8558, Japan.
Yaguchi
Ayaka
A
Yamashita
Kouwa
K
Nagaoka
Masao
M
Numazawa
Mitsuteru
M
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy
D047072:Aromatase Inhibitors; D000735:Androstenedione; D001141:Aromatase