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Published in: Inflammation 3/2017

01-06-2017 | ORIGINAL ARTICLE

2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

Authors: Clementina M. M. Santos, Daniela Ribeiro, Artur M. S. Silva, Eduarda Fernandes

Published in: Inflammation | Issue 3/2017

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Abstract

In response to an inflammatory stimulus, arachidonic acid (AA), the main polyunsaturated fatty acid present in the phospholipid layer of cell membranes, is released and metabolized to a series of eicosanoids. These bioactive lipid mediators of inflammation arise physiologically through the action of the enzymes 5-lipoxygenase (5-LOX) and cyclooxygenases (constitutive COX-1 and inducible COX-2). It is believed that dual inhibition of 5-LOX and COXs may have a higher beneficial impact in the treatment of inflammatory disorders rather than the inhibition of each enzyme. With this demand for new dual-acting anti-inflammatory agents, a range of 2,3-diarylxanthones were tested through their ability to interact in the AA metabolism. In vitro anti-inflammatory activity was evaluated through the inhibition of 5-LOX-catalyzed leukotriene B4 (LTB4) formation in human neutrophils and inhibition of COX-1- and COX-2-catalyzed prostaglandin E2 (PGE2) formation in human whole blood. The results showed that some of the studied arylxanthones were able to prevent LTB4 production in human neutrophils, in a concentration-dependent manner. The xanthone with a 2-catechol was the most active one (IC50 ∼ 9 μM). The more effective arylxanthones in preventing COX-1-catalyzed PGE2 production presented IC50 values from 1 to 7 μM, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE2 catalyzed by COX-2, up to the maximum concentration of 100 μM. The ability of the tested 2,3-diarylxanthones to interact with both 5-LOX and COX-1 pathways constitutes an important step in the research of novel dual-acting anti-inflammatory drugs.
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Metadata
Title
2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways
Authors
Clementina M. M. Santos
Daniela Ribeiro
Artur M. S. Silva
Eduarda Fernandes
Publication date
01-06-2017
Publisher
Springer US
Published in
Inflammation / Issue 3/2017
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-017-0540-6

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