title: Profiling of enantiopure drugs towards aryl hydrocarbon (AhR), glucocorticoid (GR) and pregnane X (PXR) receptors in human reporter cell lines.
abstract: In the past decade, a large number of enantiopure drugs were introduced to clinical practice, since improved therapeutic effects were demonstrated for one of the enantiomers from originally racemic drug. While the therapeutic effects and safety of enantiopure drugs were tested prior to their approval, various biological enantiospecific activities of these, often "old" drugs, remain to be elucidated. In the current paper, we examined enantiospecific effects of clinically used enantiopure drugs containing one chiral center in the structure (i.e. zopiclone, tamsulosin, tolterodine, modafinil, citalopram) towards aryl hydrocarbon (AhR), glucocorticoid (GR) and pregnane X (PXR) receptors in human reporter cell lines. The cytotoxicity (IC50), agonist (EC50) and antagonist effects (IC50) of R-form, S-form and racemic mixture for each tested drugs were determined and compared in AhR-, GR- and PXR-gene reporter cell lines. Since AhR, GR and PXR are key regulators of drug metabolism, energy metabolism, immunity and play many other physiological functions, the data presented here might be of toxicological significance.
authors: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
authors: Aneta
authors: A
authors: Novotna
authors: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
authors: Alzbeta
authors: A
authors: Kamenickova
authors: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
authors: Michaela
authors: M
authors: Pecova
authors: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
authors: Martina
authors: M
authors: Korhonova
authors: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic.
authors: Iveta
authors: I
authors: Bartonkova
authors: Department of Cell Biology and Genetics, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic. Electronic address: moulin@email.cz.
authors: Zdenek
authors: Z
authors: Dvorak
mesh_terms: D053961:Azabicyclo Compounds / Q000737:chemistry / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D015283:Citalopram / Q000737:chemistry / Q000494:pharmacology; D003408:Cresols / Q000737:chemistry / Q000494:pharmacology; D017930:Genes, Reporter / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D000077408:Modafinil; D010665:Phenylpropanolamine / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011987:Receptors, Steroid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D000077409:Tamsulosin; D000068737:Tolterodine Tartrate
chemical_list: D053961:Azabicyclo Compounds; D001559:Benzhydryl Compounds; D003408:Cresols; D010879:Piperazines; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D013449:Sulfonamides; C515050:zopiclone; D015283:Citalopram; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; D000077409:Tamsulosin; D000077408:Modafinil
keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; AhR; Chiral drugs; Cytotoxicity; DEX; Enantiospecificity; GR; Gene reporter assay; PXR; RIF; RU486; TCDD; Xenoreceptors; aryl hydrocarbon receptor; dexamethasone; glucocorticoid receptor; mifepristone; pregnane X receptor; rifampicin