Publication in European Journal of Medicinal Chemistry

The studied gold(I) triphenylphosphane complexes containing 9-deazahypoxanthine derivatives displayed anti-glucocorticoid effects, as revealed by inhibition of dexamethasone-inducible transcriptional activity of glucocorticoid receptor and down-regulation of tyrosine aminotransferase. All the compounds slightly and dose dependently activated pregnane X receptor and aryl hydrocarbon receptor, and moderately induced CYP3A4 and CYP1A1/2 genes in human hepatocytes and LS180 cells. The complexes antagonized basal and ligand-activated androgen receptor and vitamin D receptor, indicating inverse agonist behaviour. Both basal and thyroid hormone inducible transcriptional activity of thyroid receptor 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 cancer cells.