NDLI: Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry.

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Development of a functional assay to detect inhibitors of Plasmodium falciparum glutathione reductase utilizing liquid chromatography-mass spectrometry.

Content Provider	Semantic Scholar
Author	Burkard, Lexi Scheuermann, Alexis Simithy, Johayra Calderón, Angela I.
Copyright Year	2016
Abstract	Plasmodium falciparum (Pf) like most other organisms, has a sophisticated antioxidant system, part of which includes glutathione reductase (GR). GR works by recycling toxic glutathione disulfide to glutathione, thereby reducing reactive oxygen species and making a form of glutathione (GSH) the parasite can use. Inhibition of this enzyme in Pf impedes parasite growth. In addition, it has been confirmed that PfGR is not identical to human GR. Thus, PfGR is an excellent target for antimalarial drug development. A functional assay utilizing liquid chromatography-mass spectrometry was developed to specifically identify and evaluate inhibitors of PfGR. Using recombinant PfGR enzyme and 1,4-naphthoquinone (1) as a reference compound and 4-nitrobenzothiadiazole (2) and methylene blue (3) as additional compounds, we quantified the concentration of GSH produced compared with a control to determine the inhibitory effect of these compounds. Our results coincide with that presented in literature: compounds 1-3 inhibit PfGR with IC50 values of 2.71, 8.38, and 19.23 µm, respectively. Good precision for this assay was exhibited by low values of intraday and interday coefficient of variation (3.1 and 2.4%, respectively). Thus, this assay can be used to screen for other potential inhibitors of PfGR quickly and accurately.
File Format	PDF HTM / HTML
DOI	10.1002/bmc.3580
PubMed reference number	26257195
Journal	Medline
Volume Number	30
Issue Number	4
Alternate Webpage(s)	http://www.auburn.edu/undgres/documents/aujus/2015/highlights/highlight12.pdf
Alternate Webpage(s)	https://doi.org/10.1002/bmc.3580
Journal	Biomedical chromatography : BMC
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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