M. Numazawa et al., 19-oxygenated derivatives of androst-4-ene-6,17-dione and androst-5-ene-4,17-dione as catalytic probes for the active site of aromatase, BIOL PHAR B, 22(10), 1999, pp. 1134-1136
To gain insight into the binding manner of androst-4-ene-6,17-dione (4) and
its 5-en-4-one analog 9, good competitive inhibitors of aromatase, in the
active site of the enzyme, their 19-oxygenated derivatives Here evaluated a
s inhibitors of human placental aromatase, The 19-hydroxysteroids 6, 7, and
10 and the 19-oxo analogs 8 and 12 were much poorer competitive inhibitors
than their corresponding parent 19-methyl steroids. Conversion of the 17-k
eto inhibitors 4, 6, and 10 to the 17 beta-ols 5, 7, and 11, respectively,
markedly decreased their affinity to the enzyme. The results suggest that s
teroids 3 and 9 would bind to the active site in a similar manner to that i
nvolved in the binding of the substrate androstenedione (1).