title: Inhibition of LOX by flavonoids: a structure-activity relationship study.
abstract: The lipoxygenase (LOX) products have been identified as mediators of a series of inflammatory diseases, namely rheumatoid arthritis, inflammatory bowel disease, psoriasis, allergic rhinitis, atherosclerosis and certain types of cancer. Hence, LOX inhibitors are of interest for the modulation of these phenomena and resolution of the inflammatory processes. During LOX activity, peroxyl radical complexes are part of the reaction and may function as sources of free radicals. Thus antioxidants, such as flavonoids, capable of inhibiting lipid peroxidation and scavenging free radicals, may act as LOX inhibitors. The aim of this work was to assess the structure-activity relationship among a series of flavonoids concerning 5-LOX inhibition, through a systematic study of the inhibition of the formation of LTB4 in human neutrophils. The type of inhibition of the flavonoids was further studied using soybean LOX, type I, and Saturation Transfer Difference (1)H NMR (STD-(1)H NMR) was used to characterize the binding epitopes of the compounds to LOX-1. The obtained results reinforce flavonoids as effective inhibitors of LTB4 production in human neutrophils. It was also possible to establish a structure/activity relationship for the inhibitory activity and the type of inhibition.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ribeiro
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal.
authors.forename: Marisa
authors.initials: M
authors.lastname: Freitas
authors.affiliation: Departamento de Química & QOPNA, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tomé
authors.affiliation: Departamento de Química & QOPNA, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Artur M S
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Hematologia Clínica, Hospital Geral de Santo António, 4050-011 Porto, Portugal.
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
authors.affiliation: Departamento de Química, REQUIMTE/CQFB, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Lisboa, Portugal.
authors.forename: Eurico J
authors.initials: EJ
authors.lastname: Cabrita
authors.affiliation: Departamento de Química, REQUIMTE/CQFB, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Lisboa, Portugal.
authors.forename: M Manuel B
authors.initials: MM
authors.lastname: Marques
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal. Electronic address: egracas@ff.up.pt.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Fernandes
mesh_terms: D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008084:Lipoxygenase / Q000378:metabolism*; D015394:Molecular Structure; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism; D013025:Glycine max / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D007975:Leukotriene B4; D008084:Lipoxygenase
keywords: 5-LOX inhibition; Flavonoids; Neutrophils; Saturation transfer difference (1)H NMR; Soybean LOX-1