Discovery of the first non-planar flavonoid that can strongly inhibit xanthine oxidase: Protoapigenone 1′-O-propargyl ether

Attila Hunyadi, Ana Martins, Balazs Danko, Da Wei Chuang, Patrick Trouillas, Fang Rong Chang, Yang Chang Wu, G. Falkay

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Xanthine oxidase (XO) is a key enzyme in purine metabolism with an important role in various pathologies. Several flavonoids have been reported for their capacity to inhibit this enzyme, and, for these compounds, the ability to adopt a planar 3D structure has been accepted as fundamental prerequisite for such activity. Here we report the in vitro investigation of a series of non-planar protoflavone derivatives as XO inhibitors, among which protoapigenone 1′-O-propargyl ether was found to be an efficient competitive inhibitor of the enzyme with an IC50 value of 3.61 μM, significantly (p 50 = 8.72 μM). Methoxy substitution at C-7, however, resulted in complete loss of activity. In silico docking supported the observed structure-activity relationships, based on which a 'planar structure' itself can no longer be considered as a criterion for flavonoid-type inhibitors of XO.

Original languageEnglish
Pages (from-to)6529-6532
Number of pages4
JournalTetrahedron Letters
Volume54
Issue number48
DOIs
Publication statusPublished - Nov 27 2013

Fingerprint

Xanthine Oxidase
Flavonoids
Enzyme Inhibitors
Pathology
Enzymes
Structure-Activity Relationship
Metabolism
Computer Simulation
Inhibitory Concentration 50
Substitution reactions
Derivatives
propargyl ether
protoapigenone

Keywords

  • Docking study
  • Flavonoid
  • Protoapigenone
  • Protoflavone
  • Structure-activity relationships
  • Xanthine oxidase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Discovery of the first non-planar flavonoid that can strongly inhibit xanthine oxidase : Protoapigenone 1′-O-propargyl ether. / Hunyadi, Attila; Martins, Ana; Danko, Balazs; Chuang, Da Wei; Trouillas, Patrick; Chang, Fang Rong; Wu, Yang Chang; Falkay, G.

In: Tetrahedron Letters, Vol. 54, No. 48, 27.11.2013, p. 6529-6532.

Research output: Contribution to journalArticle

Hunyadi, Attila ; Martins, Ana ; Danko, Balazs ; Chuang, Da Wei ; Trouillas, Patrick ; Chang, Fang Rong ; Wu, Yang Chang ; Falkay, G. / Discovery of the first non-planar flavonoid that can strongly inhibit xanthine oxidase : Protoapigenone 1′-O-propargyl ether. In: Tetrahedron Letters. 2013 ; Vol. 54, No. 48. pp. 6529-6532.
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AU - Danko, Balazs

AU - Chuang, Da Wei

AU - Trouillas, Patrick

AU - Chang, Fang Rong

AU - Wu, Yang Chang

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