Inhibition of LOX by flavonoids: A structure-activity relationship study

Daniela Ribeiro, Marisa Freitas, Sara M. Tome, Artur M. S. Silva, Graça Porto, Eurico J. Cabrita, Maria Manuel Martinho Sequeira Barata Marques, Eduarda Fernandes

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 H-1 NMR (STD-H-1 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. (C) 2013 Elsevier Masson SAS. All rights reserved.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume72
DOIs
Publication statusPublished - 24 Jan 2014

Keywords

  • Flavonoids
  • Neutrophils
  • 5-LOX inhibition
  • Soybean LOX-1
  • Saturation transfer difference H-1 NMR
  • TRANSFER DIFFERENCE NMR
  • ANTIINFLAMMATORY ACTIVITY
  • LIGAND-BINDING
  • HUMAN-SKIN
  • OH GROUPS
  • STD-NMR
  • LIPOXYGENASE
  • 5-LIPOXYGENASE
  • ANTIOXIDANT
  • QUERCETIN

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