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J Enzyme Inhib Med Chem. 2010 Dec;25(6):854-62. doi: 10.3109/14756366.2010.486793. Epub 2010 Jun 3.

Glutathione transferase from Plasmodium falciparum--interaction with malagashanine and selected plant natural products.

Author information

1
Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, Mount Pleasant, Harare, Zimbabwe.

Abstract

A glutathione transferase (PfGST) isolated from Plasmodium falciparum has been associated with chloroquine resistance. A range of natural products including malagashanine (MG) were screened for inhibition of PfGST by a GST assay with 1-chloro-2,4-dinitrobenzene as a substrate. Only the sesquiterpene (JBC 42C), the bicoumarin (Tral-1), ellagic acid and curcumin, were shown to be potent inhibitors of PfGST with IC(50) values of 8.5, 12, 50 and 69 μM, respectively. Kinetic studies were performed on PfGST using ellagic acid as an inhibitor. Uncompetitive and mixed types of inhibition were obtained for glutathione (GSH) and 1-chloro-2, 4-dinitrobenzene (CDNB). The K(i) for GSH and CDNB were -0.015 μM and 0.011 μM, respectively. Malagashanine (100 µM) only reduced the activity of PfGST to 80% but showed a time-dependent inactivation of PfGST with a t(1/2) of 34 minutes compared to >120 minutes in the absence of MG or in the presence of 5 mM GSH. This work facilitates the understanding of the interaction of PfGST with some plant derived compounds.

PMID:
20521884
DOI:
10.3109/14756366.2010.486793
[Indexed for MEDLINE]

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