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

51 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

Cite this

Ribeiro, Daniela ; Freitas, Marisa ; Tome, Sara M. ; Silva, Artur M. S. ; Porto, Graça ; Cabrita, Eurico J. ; Marques, Maria Manuel Martinho Sequeira Barata ; Fernandes, Eduarda. / Inhibition of LOX by flavonoids : A structure-activity relationship study. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 72. pp. 137-145.
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Inhibition of LOX by flavonoids : A structure-activity relationship study. / Ribeiro, Daniela; Freitas, Marisa; Tome, Sara M.; Silva, Artur M. S.; Porto, Graça; Cabrita, Eurico J.; Marques, Maria Manuel Martinho Sequeira Barata; Fernandes, Eduarda.

In: European Journal of Medicinal Chemistry, Vol. 72, 24.01.2014, p. 137-145.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of LOX by flavonoids

T2 - A structure-activity relationship study

AU - Ribeiro, Daniela

AU - Freitas, Marisa

AU - Tome, Sara M.

AU - Silva, Artur M. S.

AU - Porto, Graça

AU - Cabrita, Eurico J.

AU - Marques, Maria Manuel Martinho Sequeira Barata

AU - Fernandes, Eduarda

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PY - 2014/1/24

Y1 - 2014/1/24

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AB - 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.

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KW - TRANSFER DIFFERENCE NMR

KW - ANTIINFLAMMATORY ACTIVITY

KW - LIGAND-BINDING

KW - HUMAN-SKIN

KW - OH GROUPS

KW - STD-NMR

KW - LIPOXYGENASE

KW - 5-LIPOXYGENASE

KW - ANTIOXIDANT

KW - QUERCETIN

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DO - 10.1016/j.ejmech.2013.11.030

M3 - Article

VL - 72

SP - 137

EP - 145

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

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