Biochemical Studies of Estr-4-ene-3,6,17-trione and 5α-Androstan-17-ones with or without a Carbonyl Function at C-3 and/or C-6 as Aromatase Inhibitors

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19-Nor (2) and 5α-reduced (3) derivatives of androst-4-ene-3,6,17-trione (1) as well as 5α-androstan-17-ones 4-6 were tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids except 5α-6-one 4 were fair to good competitive inhibitors of the enzyme, with apparent K_i's ranging from 50 to 820 nM in which 5α-3-one 5 was the most potent among them. The inhibitory activities of the 19-nor and 5α-reduced derivatives (2 and 3) were less potent than that of the parent compound 1. Inhibitor 2 caused a time-dependent, pseudo-first-order inactivation of aromatase activity with a rate constant for inactivation of 0.148 min^<-1> in the presence of NADPH in air. The substrate androstenedione prevented the inactivation and L-cysteine did not protect aromatase from the inactivation.
公益社団法人日本薬学会の論文
1995-04-15