A spectroscopic investigation of the binding interactions between 4,5-dihydroxyxanthone and heme

J. Xu Kelly, R. Winter, Michael Riscoe, D. H. Peyton

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

In order to investigate one possible mechanism by which xanthones inhibit growth of malaria-causing Plasmodium parasites, optical and NMR spectroscopic studies were performed on a prototypic xanthone, 4,5-dihydroxyxanthone (45X2), upon its complexation to heme. The 45X2·heme complex stoichiometry in aqueous solution was found to be 1:2; this interaction was non-cooperative, and exhibited a very similar heme complex dissociation constant (Kd = 5.1 × 10-6) as observed for the common antimalarial agents, chloroquine and quinine. The 45X2·heme2 complex formation was found to be both pH- and solvent-dependent, with clear evidence of the xanthone carbonyl moiety coordinating with the iron of heme. Hydrogen bonding between the hydroxyl groups of 45X2 and the propionate side chains of heme, as well as π-π stacking between both aromatic systems appeared to contribute to the overall stability of the 45X2·heme2 complex, as judged by 1H NMR. It was concluded that 45X2 forms a complex with a heme dimer in aqueous solution, and that this interaction can be generalized to account for its in vivo detrimental effect of parasite growth through an effective inhibition of hemozoin aggregate formation.

Original languageEnglish (US)
Pages (from-to)617-625
Number of pages9
JournalJournal of Inorganic Biochemistry
Volume86
Issue number2-3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Heme
Parasites
Nuclear magnetic resonance
Plasmodium malariae
Xanthones
Quinine
Propionates
Chloroquine
Antimalarials
Hydrogen Bonding
Growth
Complexation
Stoichiometry
Hydroxyl Radical
Dimers
Hydrogen bonds
Iron
4,5-dihydroxy-xanthone
xanthone

Keywords

  • Chemotherapy
  • Heme
  • Malaria
  • NMR
  • Plasmodium falciparum
  • Xanthone

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

A spectroscopic investigation of the binding interactions between 4,5-dihydroxyxanthone and heme. / Xu Kelly, J.; Winter, R.; Riscoe, Michael; Peyton, D. H.

In: Journal of Inorganic Biochemistry, Vol. 86, No. 2-3, 2001, p. 617-625.

Research output: Contribution to journalArticle

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