TY  - JOUR
PY  - 1990//
TI  - Competitive inhibition and suicide inactivation of human placental aromatase by androst-4-ene-3,6-dione derivatives and 3 alpha-methoxyandrost-4-ene-6,17-dione
JO  - Chemical and pharmaceutical bulletin
A1  - Numazawa, M.
A1  - Mutsumi, A.
A1  - Kigawa, H.
SP  - 3076
EP  - 3080
VL  - 38
IS  - 11
N2  - 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.<p /> <p>Language: en</p>
LA  - en
SN  - 0009-2363
UR  - http://dx.doi.org/10.1248/cpb.38.3076
ID  - ref1
ER  -