Xanthones as antimalarial agents; studies of a possible mode of action
Language: 
English
Abstract: 

We recently demonstrated that 2,3,4,5,6-pentahydroxyxanthone (X5) inhibits the in vitro growth of both chloroquine-sensitive and multidrug-resistant strains of P. falciparum. To study the molecular basis of its antimalarial action, we tested X5 and selected hydroxyxanthone analogs as inhibitors of in vitro heme polymerization in a low ionic strength phosphate solution at mildly acidic pH. We found that addition of 1 Eq. of X5 resulted in complete inhibition of polymerization in this system whereas addition of up to 40 Eqs. of standard antimalarial compounds (chloroquine, primaquine, quinacrine, artemisinin and methylene blue) had no such effect although these compounds did co-precipitate with heme. The antimalarial potency of the hydroxyxanthones correlated well with their ability to inhibit in vitro heme polymerization in our assay, suggesting that these compounds exert their antimalarial action by preventing hemozoin formation. Based on the observed structure-activity relationships, we propose a model displaying possible interactions between hydroxyxanthones and heme.

Author(s): 
Ignatushchenko, M. V.
Winter, R. W.
Bächinger, H. P.
Hinrichs, D. J.
Riscoe, M. K.
Item Type: 
Journal Article
Publication Title: 
FEBS letters
Journal Abbreviation: 
FEBS Lett.
Publication Date: 
6/2/1997
Publication Year: 
1997
Pages: 
67-73
Volume: 
409
Issue: 
1
ISSN: 
0014-5793
Library Catalog: 
PubMed
Extra: 
PMID: 9199506

Turabian/Chicago Citation

M. V. Ignatushchenko, R. W. Winter, H. P. Bächinger, D. J. Hinrichs and M. K. Riscoe. 6/2/1997. "Xanthones as antimalarial agents; studies of a possible mode of action." FEBS letters 409: 1: 67-73.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 0014-5793 | volume = 409 | pages = 67-73 | last = Ignatushchenko | first = M. V. | coauthors = Winter, R. W., Bächinger, H. P., Hinrichs, D. J., Riscoe, M. K. | title = Xanthones as antimalarial agents; studies of a possible mode of action | journal = FEBS letters | date = 6/2/1997 | pmid = | pmc = }} </ref>