title: Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathways.
abstract: Cyclooxygenases (COXs) are the key enzymes in the biosynthesis of prostanoids. COX-1 is a constitutive enzyme while the expression of COX-2 is highly stimulated in the event of inflammatory processes, leading to the production of large amounts of prostaglandins (PGs), in particular PGE(2) and PGI(2), which are pro-inflammatory mediators. Lipoxygenases (LOXs) are enzymes that produce hydroxy acids and leukotrienes (LTs). 5-LOX metabolizes arachidonic acid to yield, among other products, LTB(4), a potent chemoattractant mediator of inflammation. The aim of the present work was to evaluate the anti-inflammatory potential of 2-styrylchromones (2-SC), a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), by studying their COX-1 and COX-2 inhibitory capacity as well as their effects on the LTB(4) production by stimulated human polymorphonuclear leukocytes (PMNL). Some of the tested 2-SC were able to inhibit both COX-1 activity and LTB(4) production which makes them dual inhibitors of the COX and 5-LOX pathways. The most effective compounds in this study were those having structural moieties with proved antioxidant activity (3',4'-catechol and 4'-phenol substituted B-rings). This type of compounds may exhibit anti-inflammatory activity with a wider spectrum than that of classical non-steroidal anti-inflammatory drugs (NSAIDs) by inhibiting 5-LOX product-mediated inflammatory reactions, towards which NSAIDs are ineffective.
authors.affiliation: REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Gomes
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
authors.forename: Artur M S
authors.initials: AM
authors.lastname: Silva
authors.forename: Diana C G A
authors.initials: DC
authors.lastname: Pinto
authors.forename: Clementina M M
authors.initials: CM
authors.lastname: Santos
authors.forename: José A S
authors.initials: JA
authors.lastname: Cavaleiro
authors.forename: José L F C
authors.initials: JL
authors.lastname: Lima
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology* / Q000633:toxicity; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000502:physiology*; D013343:Styrenes / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002867:Chromones; D052246:Cyclooxygenase 2 Inhibitors; D013343:Styrenes; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2