Author/Editor		Brožič, Petra; Golob, Barbara; Gomboc, Nataša; Lanišnik-Rižner, Tea; Gobec, Stanislav
Title		Cinnamic acids as new inhibitors of 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3)
Type		članek
Source		Mol Cell Endocrinol
Vol. and No.		Letnik 248, št. 1-2
Publication year		2006
Volume		str. 233-5
Language		eng
Abstract		17beta-Hydroxysteroid dehydrogenase type 5 (AKR 1C3) that is involved in the pre-receptor regulation of androgen and estrogen action in the human is an emerging therapeutic target in the treatment of hormone-dependent forms of cancer, such as prostate cancer, breast cancer and endometrial cancer. To discover novel inhibitors, we tested the effect of a series of cinnamic acids on the reductive activity of the human recombinant AKR1C3. The compounds were evaluated in a spectrophotometric assay using 9,10-phenanthrenequinone as a substrate. The best inhibitor in the series was alfa-methylcinnamic acid (ICSO=6.4 wM). Also, unsubstituted cinnamic acid was a good inhibitor of AKR1C3 (IC50=50 miM). Small hydrophobic substituents of the phenyl ring did not alter the activity; however, substitution with polar groups decreased the potency of inhibition. The most active compounds in this series represent promising starting points for further structural modifications in the search for more potent inhibitors of AKR1C3.
Descriptors		17-HYDROXYSTEROID DEHYDROGENASES ENZYME INHIBITORS CINNAMATES RECOMBINANT PROTEINS PHENANTHRENES QUINONES SPECTROPHOTOMETRY TRANSFECTION