• Home
  • Search Results
  • Synthesis and biological evaluation of (6- and 7-phenyl) coumarin derivatives as selective nonsteroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1.

Synthesis and biological evaluation of (6- and 7-phenyl) coumarin derivatives as selective nonsteroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1.

Journal of medicinal chemistry (2010-12-09)
Stefan Starcević, Petra Brozic, Samo Turk, Jozko Cesar, Tea Lanisnik Rizner, Stanislav Gobec
ABSTRACT

17β-Hydroxysteroid dehydrogenase type 1 (17β-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 17β-HSD1 in estrogen-responsive tissues is related to the development of hormone-dependent diseases, such as breast cancer and endometriosis; thus, 17β-HSD1 represents an attractive target for the development of new therapies. We have discovered that simple coumarines 1 and 2 significantly inhibit 17β-HSD1 in a recombinant enzyme assay, with high selectivity against 17β-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 17β-HSD1. The best inhibitor in the series proved to be 6a, with an IC(50) of 270 nM, and with exceptional selectivity for 17β-HSD1 over 17β-HSD2 and against the α and β estrogen receptors.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Umbelliferone, 99%
Sigma-Aldrich
Equilin
Sigma-Aldrich
7-Methoxycoumarin, ≥98%
Sigma-Aldrich
Umbelliferone, suitable for fluorescence indicator, ≥98.0% (HPLC)

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.