Citation

Numazawa M, Mutsumi A, Kigawa H. Chem. Pharm. Bull. (Tokyo) 1990; 38(11): 3076-3080.

Copyright

(Copyright © 1990, Pharmaceutical Society of Japan)

DOI

10.1248/cpb.38.3076

PMID

2085891

Abstract

Androst-4-ene-3,6-dione derivatives 2-4 and 3 alpha-methoxy-4-en-6-one steroid 7 were prepared and tested for their ability to inhibit aromatase in human placental microsomes. The 16 alpha-bromide 2, the 16 alpha-alcohol 3, and the 3 alpha-methoxide 7 of this series were effective competitive inhibitors of aromatase with apparent Ki's of 150 nM, 1.18 microM, and 700 nM. Compound 2 caused a time-dependent, biphasic loss of aromatase activity in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) while compound 7 caused a time-dependent, pseudo-first order inactivation of the activity, with kinact's of 0.417 and 0.036 min-1 for compounds 2 and 7. NADPH and oxygen were required for the time-dependent inactivation and the substrate, androst-4-ene-3,17-dione, prevented it in each case.

Language: en

Keywords

Androstenedione; Aromatase Inhibitors; Binding Sites; Female; Humans; Placenta; Pregnancy; Structure-Activity Relationship