14 alpha-hydroxyandrost-4-ene-3,6,17-trione as a mechanical-based irreversible inhibitor of estrogen biosynthesis.
Various derivatives of androst-4-ene-3,17-dione derived from microbial transformation were evaluated as inhibitors of human placental aromatase. 14 alpha-Hydroxyandrost-4-ene-3,6,17-trione was the most potent inhibitor showing a time-dependent, pseudo-first-order inactivation of aromatase in the presence of reduced nicotinamide adenine dinucleotide phosphate with apparent Ki of 1.3 microM and Kinact of 0.23 min-1. This compound also inhibited aromatase in rat ovary and suppressed serum estradiol levels in in vivo experiments.
Yoshihama
M
M
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.
Tamura
K
K
Nakakoshi
M
M
Nakamura
J
J
Fujise
N
N
Kawanishi
G
G
D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D003864:Depression, Chemical; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000737:Androstenols; D004965:Estrogen Antagonists; D004967:Estrogens; C067637:14-hydroxyandrost-4-ene-3,6,17-trione; D001141:Aromatase