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Synthesis and biological evaluation of (6- and 7-phenyl) coumarin derivatives as selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1Starčević, Štefan ...17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is an enzyme that catalyzes NADPH-dependent reduction of the weak estrogen, estrone, into the most potent estrogen, estradiol, which exerts ... proliferative effects via the estrogen receptors. Overexpression of 17beta-HSD1 in estrogen-responsive tissues is related to the development of hormone-dependent diseases, such as breast cancer and endometriosis; thus, 17beta-HSD1 represents an attractive target for the development of new therapies. We have discovered that simple coumarines 1 and 2 significantly inhibit 17beta-HSD1 in a recombinant enzyme assay, with high selectivity against 17beta-HSD2. We postulated that the introduction of various p-substituted phenyl moieties to position 6 or 7 of the coumarin core using the Suzuki-Miyaura cross-coupling reaction would provide mimetics of steroidal structures with improved inhibition of 17beta-HSD1. The best inhibitor in the series proved to be 6a, with an IC(50) of 270 nM, and with exceptional selectivity for 17beta-HSD1 over 17beta-HSD2 and against the alpha and beta estrogen receptors.Source: Journal of medicinal chemistry. - ISSN 0022-2623 (Vol. 54, issue 1, 2011, str. 248-261)Type of material - article, component partPublish date - 2011Language - englishCOBISS.SI-ID - 27732441
Author
Starčević, Štefan |
Brožič, Petra |
Turk, Samo |
Cesar, Jožko |
Lanišnik-Rižner, Tea |
Gobec, Stanislav, 1970-
Topics
17-Hydroxysteroid Dehydrogenases |
Antagonists And Inhibitors |
Coumarins |
Analogs And Derivatives |
Estrogens |
Nadh Dehydrogenase |
Estradiol |
Receptors, Estrogen |
Biological Assay |
Estradiol |
NADH dehidrogenaza |
17-hidroksisteroidne dehidrogenaze |
Kumarini |
Estrogeni |
Biološki poskus |
Receptorji estrogenski
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Starčević, Štefan | 28776 |
Brožič, Petra | 27575 |
Turk, Samo | 29773 |
Cesar, Jožko | 19062 |
Lanišnik-Rižner, Tea | 11699 |
Gobec, Stanislav, 1970- | 15284 |
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