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

Article abstract of DOI:10.1248/bpb.18.555

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.

Full text of DOI:10.1248/bpb.18.555

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NII-Electronic Library Service