Interaction of 7-Alkoxycoumarins with the Aryl Hydrocarbon Receptor

Journal of Natural Products
Marco GargaroFrancesca Fallarino

Abstract

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.

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Citations

Sep 26, 2019·Chemico-biological Interactions·Clarissa Feltrin, Cláudia Maria Oliveira Simões
Dec 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca PreziusoSerena Fiorito

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