Interaction of 7-Alkoxycoumarins with the Aryl Hydrocarbon Receptor
| Autor: | Vito Alessandro Taddeo, Serena Fiorito, Salvatore Genovese, Francesca Fallarino, Marco Gargaro, Carsten B. Schmidt-Weber, Antonella Turco, Paolo Puccetti, Francesco Epifano, Matteo Pirro |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Pharmaceutical Science Ligands Umbelliferone 01 natural sciences Analytical Chemistry Mice 03 medical and health sciences chemistry.chemical_compound Coumarins Drug Discovery Animals Luciferase Receptor Transcription factor Pharmacology Molecular Structure biology 010405 organic chemistry Chemistry Activator (genetics) Drug Discovery3003 Pharmaceutical Science Organic Chemistry Cell Differentiation Aryl hydrocarbon receptor Coumarin Complementary and Alternative Medicine2708 Dermatology 0104 chemical sciences 030104 developmental biology Receptors Aryl Hydrocarbon Complementary and alternative medicine Biochemistry biology.protein Molecular Medicine 3003 Signal transduction Signal Transduction |
| Popis: | The aryl hydrocarbon receptor (AhR) is a transcription factor activated by a vast array of natural and synthetic ligands. It plays a pivotal role in numerous physiological and pathological responses, such as cell proliferation and differentiation, induction of xenobiotic metabolizing enzymes, response to environmental toxins, and several others. In this study, we investigated the ability of some natural compounds (oxyprenylated ferulic acid and umbelliferone derivatives) and their semisynthetic analogues (e.g., differently substituted 7-alkoxycoumarins) to activate AhR, using a reporter luciferase assay. Among them, we found that 7-isopentenyloxycoumarin was the best AhR activator. Boropinic acid, 7-but-2'-enyloxycoumarin, 7-(2',2'-dimethyl-n-propyloxy)coumarin, 7-benzyloxycoumarin, and 7-(3'-hydroxymethyl-3'-methylallyloxy)coumarin were also active, although to a lesser extent. All the compounds were also analyzed for their ability to inhibit AhR activation, using a reference ligand, 6-formylindolo[3,2-b]carbazole. Data recorded in the present investigation pointed out the importance of a 3,3-dimethylallyloxy side chain attached to the coumarin ring core as a key moiety for AhR activation. |
| Databáze: | OpenAIRE |
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