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

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Santos, CMM (Author) Other; Ribeiro, D (Author) Other; Silva, AMS (Author) Other; Eduarda Fernandes (Author) FFUP

Journal

Title: Inflammation

Vol. 40

Pages: 956-964

ISSN: 0360-3997

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00M-HPV

DOI: 10.1007/s10753-017-0540-6

Abstract (EN): 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 B-4 (LTB4) formation in human neutrophils and inhibition of COX-1- and COX-2-catalyzed prostaglandin E-2 (PGE(2)) 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 similar to 9 mu M). The more effective arylxanthones in preventing COX-1-catalyzed PGE(2) production presented IC50 values from 1 to 7 mu M, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE(2) catalyzed by COX-2, up to the maximum concentration of 100 mu M. 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9