Synthesis and evaluation of 17 alpha-(carboranylalkyl)estradiols as ligands for estrogen receptors alpha and beta

0422820 - ÚMG 2014 RIV CH eng J - Journal Article
Sedlák, David - Eignerová, Barbara - Dračínský, Martin - Janoušek, Zbyněk - Bartůněk, Petr - Kotora, Martin
Synthesis and evaluation of 17 alpha-(carboranylalkyl)estradiols as ligands for estrogen receptors alpha and beta.
Journal of Organometallic Chemistry. Roč. 747, 1.12.2013 (2013), s. 178-183. ISSN 0022-328X. E-ISSN 1872-8561
R&D Projects: GA MŠMT(CZ) LC06070; GA MŠMT(CZ) LC06077; GA MŠMT LM2011022; GA ČR GA204/09/1905
Institutional support: RVO:68378050 ; RVO:61388963
Keywords : carborane * estradiol * metathesis * estrogen receptor * steroid ligand
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 2.302, year: 2013

A series of 17 alpha-(carboranylalkyl)estradiols was synthesized using cross-metathesis reaction of 17 alpha-allyl- and 17 alpha-vinylestradiols with allylcarboranes catalyzed by Hoveyda-Grubbs 2nd generation catalyst. The prepared estradiol derivatives were tested in the panel of cell-based reporter assays including all steroid receptors. The compounds mainly activated estrogen receptors alpha and beta and tended to be weakly selective for ER alpha. Besides ER alpha and ER beta, we have also detected a weak agonistic activity on AR and PR at micromolar concentrations. We didn't observe any antagonistic effect with the exception of two receptors: GR and MR which were inhibited with some of the tested ligands. However, the inhibition was detectable at concentrations exceeding by far those needed to activate estrogen receptors. (C) 2013 Elsevier B. V. All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0229015