Structure activity relationship studies on cytotoxicity and the effects on steroid receptors of AB-functionalized cholestanes
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26976651
DOI
10.1016/j.jsbmb.2016.03.017
PII: S0960-0760(16)30063-2
Knihovny.cz E-resources
- Keywords
- Antiproliferative activity, Apoptosis, Cell cycle, Cholestane derivatives, Steroid receptor, Structure-activity relationship,
- MeSH
- Apoptosis MeSH
- Cell Cycle drug effects MeSH
- Cholestanes chemistry pharmacology MeSH
- Inhibitory Concentration 50 MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Receptors, Steroid metabolism MeSH
- Cell Survival MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cholestanes MeSH
- Antineoplastic Agents MeSH
- Receptors, Steroid MeSH
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.
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