Pleiotropic effects of gold(I) mixed-ligand complexes of 9- deazahypoxanthine on transcriptional activity of receptors for steroid hormones, nuclear receptors and xenoreceptors in human hepatocytes and cell lines
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33159495" target="_blank" >RIV/61989592:15310/16:33159495 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S022352341630472X" target="_blank" >http://www.sciencedirect.com/science/article/pii/S022352341630472X</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2016.05.064" target="_blank" >10.1016/j.ejmech.2016.05.064</a>
Alternative languages
Result language
angličtina
Original language name
Pleiotropic effects of gold(I) mixed-ligand complexes of 9- deazahypoxanthine on transcriptional activity of receptors for steroid hormones, nuclear receptors and xenoreceptors in human hepatocytes and cell lines
Original language description
Development of metal-based compounds is an important research avenue in anti-cancer and anti-inflammatory drug discovery. Here we examined the effects of three gold (I) mixed-ligand complexes with the general formula [Au(L-n)(PPh3)] (1, 2, 3) involving triphenylphosphine (PPh3) and a deprotonated form of O-substituted derivatives of 9-deazahypoxanthine (L-n) on the transcriptional activity of aryl hydrocarbon receptor (AhR), androgen receptor (AR), glucocorticoid receptor (GR), thyroid receptor (TR), pregnane X receptor (PXR) and vitamin D receptor (VDR), employing gene reporter assays. In addition, we measured mRNA (RT-PCR) and protein (western blot) expression of target genes for those receptors, including drug-metabolizing P450s, in primary human hepatocytes and cancer cell lines LS180 and HepG2. The tested compounds displayed anti-glucocorticoid effects, as revealed by inhibition of dexamethasone-inducible transcriptional activity of GR and down-regulation of tyrosine aminotransferase. All the compounds slightly and dose-dependently activated PXR and AhR, and moderately induced CYP3A4 and CYP1A1/2 genes in human hepatocytes and LS180 cells. The complexes antagonized basal and ligand-activated AR and VDR, indicating inverse agonist behaviour. Both basal and thyroid hormone-inducible transcriptional activity of TR was dose-dependently increased by all tested compounds. In contrast, the expression of SPOT14 mRNA was decreased by tested compounds in human hepatocytes and HepG2 cells. In conclusion, if intended for human pharmacotherapy, the potential of the complexes 1-3 to influence studied receptors should be taken in account. (C) 2016 Elsevier Masson SAS.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Medicinal Chemistry
ISSN
0223-5234
e-ISSN
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Volume of the periodical
121
Issue of the periodical within the volume
OCT
Country of publishing house
FR - FRANCE
Number of pages
11
Pages from-to
530-540
UT code for WoS article
000382269700045
EID of the result in the Scopus database
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