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Bioorg Med Chem Lett. 2013 Apr 1;23(7):2158-61. doi: 10.1016/j.bmcl.2013.01.097. Epub 2013 Jan 30.

Expression, characterization and inhibition of Toxoplasma gondii 1-deoxy-D-xylulose-5-phosphate reductoisomerase.

Author information

1
Department of Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.

Abstract

The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, is an important human pathogen. 1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is essential to the organism and therefore a target for developing anti-toxoplasmosis drugs. In order to find potent inhibitors, we expressed and purified recombinant T. gondii DXR (TgDXR). Biochemical properties of this enzyme were characterized and an enzyme activity/inhibition assay was developed. A collection of 11 compounds with a broad structural diversity were tested against TgDXR and several potent inhibitors were identified with Ki values as low as 48 nM. Analysis of the results as well as those of Escherichia coli and Plasmodium falciparum DXR enzymes revealed a different structure-activity relationship profile for the inhibition of TgDXR.

PMID:
23428849
PMCID:
PMC3602143
DOI:
10.1016/j.bmcl.2013.01.097
[Indexed for MEDLINE]
Free PMC Article

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