Novel inhibitors of 17beta-hydroxysteroid dehydrogenase type 1: templates for design.
The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the interconversion between the oxidized and reduced forms of androgens and estrogens at the 17 position. The 17beta-HSD type 1 enzyme (17beta-HSD1) catalyzes the reduction of estrone (E1) to estradiol and is expressed in malignant breast cells. Inhibitors of this enzyme thus have potential as treatments for hormone dependent breast cancer. Syntheses and biological evaluation of novel non-steroidal inhibitors designed to mimic the E1 template are reported using information from potent steroidal inhibitors. Of the templates investigated biphenyl ethanone was promising and led to inhibitors with IC(50) values in the low micromolar range.
Allan
Gillian M
GM
Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Claverton Down BA2 7AY, UK.
Vicker
Nigel
N
Lawrence
Harshani R
HR
Tutill
Helena J
HJ
Day
Joanna M
JM
Huchet
Marion
M
Ferrandis
Eric
E
Reed
Michael J
MJ
Purohit
Atul
A
Potter
Barry V L
BV
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase