title: Influence of gold(I) complexes involving adenine derivatives on major drug-drug interaction pathway.
abstract: A series of considerably anti-inflammatory active gold(I) mixed-ligand complexes, involving the benzyl-substituted derivatives of N6-benzyladenine (HLn) and triphenylphosphine (PPh3) as ligands and having the general formula [Au(Ln)(PPh3)]·xH2O (1-4; n=1-4 and x=0-1), was evaluated for the ability to influence the expression of CYP1A1/2 and CYP3A4 and transcriptional activity of glucocorticoid (GR) and aryl hydrocarbon (AhR) receptors in primary human hepatocytes and HepG2 cells. In both tests, evaluating the ability of the complexes to modulate the expression of CYP1A1, CYP1A2 and CYP3A4 in primary human hepatocytes and influence the transcriptional activity of AhR and GR in the reporter cell lines, no negative influence on the major drug-metabolizing cytochrome P450 isoenzymes and their signaling pathway (through GR and AhR receptors) was observed. These positive findings revealed another substantial evidence that could lead to utilization of the complexes as effective and relatively safe drugs for the treatment of hard-to-treat inflammation-related diseases, such as rheumatoid arthritis, comparable or even better than clinically used gold-containing drug Auranofin.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Cell Biology and Genetics, Faculty of Science, Palacký University in Olomouc, Šlechtitelů 11, CZ-783 71 Olomouc, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Dvořák
authors.forename: Aneta
authors.initials: A
authors.lastname: Novotná
authors.forename: Ján
authors.initials: J
authors.lastname: Vančo
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Trávníček
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001593:Benzyl Compounds; D002478:Cells, Cultured; D056831:Coordination Complexes / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D017930:Genes, Reporter; D006046:Gold / Q000737:chemistry*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007701:Kinetin / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011687:Purines; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D001593:Benzyl Compounds; D056831:Coordination Complexes; D009943:Organophosphorus Compounds; D011687:Purines; D018336:Receptors, Aryl Hydrocarbon; D011965:Receptors, Glucocorticoid; C061896:triphenylphosphine; D006046:Gold; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C480551:benzylaminopurine; D007701:Kinetin
keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; AhR; Aryl hydrocarbon receptor; Cytochrome P450; DEX; Drug–drug interactions; GR; Glucocorticoid receptor; Gold complexes; TCDD; aryl hydrocarbon receptor; dexamethasone; glucocorticoid receptor