Probing the hydrophobic pocket of the active site of aromatase with 4-phenoxy-7 alpha-(phenylthio)-4-androstene-3,17-dione.
In order to examine the nature of the hydrophobic pocket at the active site of aromatase, we carried out the synthesis, biochemical evaluation, and molecular modeling studies on 4-phenoxy-7 alpha-(phenylthio)-4-androstenedione 2. Aromatase inhibitory activity of 2 was found to be significantly weaker than that of the 4- and 7 alpha-mono(phenylthio)-substituted derivatives of androstenedione. These results along with those obtained from the modeling studies suggest the existence of a single hydrophobic pocket corresponding to the alpha-face in the C4, C6, C7 region of androstenedione.
Liu
X P
XP
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455, USA.
Lambert
D M
DM
Abul-Hajj
Y J
YJ
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D001141:Aromatase / Q000737:chemistry; D047072:Aromatase Inhibitors; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D011487:Protein Conformation; D013329:Structure-Activity Relationship
C096009:4-phenoxy-7-phenylthio-4-androstene-3,17-dione; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D000735:Androstenedione; D001141:Aromatase