Structure activity relationship studies on cytotoxicity and the effects on steroid receptors of AB-functionalized cholestanes

0461520 - ÚEB 2017 RIV GB eng J - Journal Article
Rárová, L. - Steigerová, J. - Kvasnica, Miroslav - Bartůněk, Petr - Křížová, K. - Chodounská, Hana - Kolář, Z. - Sedlák, David - Oklešťková, Jana - Strnad, Miroslav
Structure activity relationship studies on cytotoxicity and the effects on steroid receptors of AB-functionalized cholestanes.
Journal of Steroid Biochemistry and Molecular Biology. Roč. 159, MAY (2016), s. 154-169. ISSN 0960-0760
R&D Projects: GA MŠMT(CZ) LO1204; GA MŠMT(CZ) LO1304; GA MŠMT LO1220; GA MŠMT LM2011022; GA ČR GJ15-08202Y
Institutional support: RVO:61389030 ; RVO:61388963 ; RVO:68378050
Keywords : Antiproliferative activity * Apoptosis * Cholestane derivatives
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.561, year: 2016

Structure-activity relationship analysis and profiling of a library of AB-functionalized cholestane derivatives closely related to brassinosteroids (BRs) were performed to examine their antiproliferative activities and activities on steroid hormone receptors. Some of the compounds were found to have strong cytotoxic activity in several human normal and cancer cell lines. The presence of a 3-hydroxy or 3-oxo group and 2,3-vicinal diol or 3,4-vicinal diol moiety were found to be necessary for optimum biological activity, as well as a six-membered B ring. According to the profiling of all steroid receptors in both agonist and antagonist mode, the majority of the cholestanes were weakly active or inactive compared to the natural ligands. Estrogenic activity was detected for two compounds, two compounds possessed antagonistic properties on estrogen receptors and seven compounds showed agonistic activity. Two active cholestane derivatives were shown to strongly influence cell viability, proliferation, cell cycle distribution, apoptosis and molecular pathways responsible for these processes in hormone-sensitive/insensitive (MCF7/MDA-MB-468) breast cancer cell lines.
Permanent Link: http://hdl.handle.net/11104/0261144