title: In vitro modulatory effects of functionalized pyrimidines and piperidine derivatives on Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) activities.
abstract: The development of biologically active molecules based on molecular recognition is an attractive and challenging task in medicinal chemistry and the molecules that can activate/deactivate certain receptors are of great medical interest. In this contribution, selected pyrimidine/piperidine derivatives were synthesized and tested for the ability to activate/deactivate Aryl hydrocarbon receptor (AhR) and Glucocorticoid receptor (GR). Tested compounds are shown to activate the receptors but to much lesser extent than positive controls, dioxin and dexamethasone for Ahr and GR, respectively. However, some of them antagonized the positive controls action. Although further in vivo studies are needed to fully characterize the bioactivities of these compounds, the reported in vitro evidences demonstrate that they might be used as the modulators of AhR and GR activities.
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan.
authors.forename: Lubna
authors.initials: L
authors.lastname: Shahzadi
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan; Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Ariba
authors.initials: A
authors.lastname: Farooq
authors.affiliation: Department of Cell Biology and Genetics, Palacky University, Olomouc, Czech Republic.
authors.forename: Saima
authors.initials: S
authors.lastname: Jalil Imran
authors.affiliation: Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Católica San Antonio de Murcia (UCAM), 30107 Murcia, Spain.
authors.forename: José P
authors.initials: JP
authors.lastname: Cerón-Carrasco
authors.affiliation: Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Católica San Antonio de Murcia (UCAM), 30107 Murcia, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: den-Haan
authors.affiliation: Bioinformatics Centre, Biotech Park, Sector G, Jankipuram, Lucknow 226021, Uttar Pradesh, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Católica San Antonio de Murcia (UCAM), 30107 Murcia, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Peña-García
authors.affiliation: Bioinformatics and High Performance Computing Research Group (BIO-HPC), Universidad Católica San Antonio de Murcia (UCAM), 30107 Murcia, Spain.
authors.forename: Horacio
authors.initials: H
authors.lastname: Pérez-Sánchez
authors.affiliation: Department of Cell Biology and Genetics, Palacky University, Olomouc, Czech Republic.
authors.forename: Aneta
authors.initials: A
authors.lastname: Grycova
authors.affiliation: Department of Cell Biology and Genetics, Palacky University, Olomouc, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
authors.affiliation: Department of Cell Biology and Genetics, Palacky University, Olomouc, Czech Republic. Electronic address: radim.vrzal@email.cz.
authors.forename: Radim
authors.initials: R
authors.lastname: Vrzal
mesh_terms: D055808:Drug Discovery; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D010880:Piperidines; D011743:Pyrimidines; D018336:Receptors, Aryl Hydrocarbon; D011965:Receptors, Glucocorticoid
keywords: Antagonists; Aryl hydrocarbon receptor; Biotransformation; Glucocorticoid receptor; Immunological response; Piperidines; Pyrimidines