In vitro modulatory effects of functionalized pyrimidines and piperidine derivatives on Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) activities

• Published in: Bioorganic chemistry 2017-04, Vol.71, p.285-293
• Main Authors: Yar, Muhammad, Shahzadi, Lubna, Farooq, Ariba, Jalil Imran, Saima, Cerón-Carrasco, José P., den-Haan, Helena, Kumar, Sanjay, Peña-García, Jorge, Pérez-Sánchez, Horacio, Grycova, Aneta, Dvorak, Zdenek, Vrzal, Radim
• Format: Article
• Language: English
• Subjects: Antagonists; Aryl hydrocarbon receptor; Biotransformation; Drug Discovery; Glucocorticoid receptor; HeLa Cells; Hep G2 Cells; Humans; Immunological response; Models, Molecular; Piperidines; Piperidines - chemistry; Piperidines - pharmacology; Pyrimidines; Pyrimidines - chemistry; Pyrimidines - pharmacology; Receptors, Aryl Hydrocarbon - agonists; Receptors, Aryl Hydrocarbon - antagonists & inhibitors; Receptors, Aryl Hydrocarbon - metabolism; Receptors, Glucocorticoid - agonists; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - metabolism
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2017.02.013

[Display omitted] •Molecules that can activate/deactivate certain receptors are of great medical interest.•Selected pyrimidine/piperidine derivatives were synthesized.•The in vitro evidences demonstrate these compounds might be used as the modulators of AhR and GR activities. 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.