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Gut Microbes. 2013 Jan-Feb;4(1):66-71. doi: 10.4161/gmic.22596. Epub 2012 Nov 8.

Reprofiled drug targets ancient protozoans: drug discovery for parasitic diarrheal diseases.

Author information

1
Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, CA, USA. anjan.debnath@ucsf.edu

Abstract

Recently, we developed a novel automated, high throughput screening (HTS) methodology for the anaerobic intestinal parasite Entamoeba histolytica. We validated this HTS platform by screening a chemical library containing US Food and Drug Administration (FDA)-approved drugs and bioactive compounds. We identified an FDA-approved drug, auranofin, as most active against E. histolytica both in vitro and in vivo. Our cell culture and animal studies indicated that thioredoxin reductase, an enzyme involved in reactive oxygen species detoxification, was the target for auranofin in E. histolytica. Here, we discuss the rationale for drug development for three parasites which are major causes of diarrhea worldwide, E. histolytica, Giardia lamblia and Cryptosporidium parvum and extend our current finding of antiparasitic activity of auranofin to Entamoeba cysts, G. lamblia and C. parvum. These studies support the use of HTS assays and reprofiling FDA-approved drugs for new therapy for neglected tropical diseases.

KEYWORDS:

Cryptosporidium parvum; Entamoeba; Giardia; auranofin; diarrheal diseases; drug discovery; high throughput screen; orphan drug; protozoan parasites; thioredoxin reductase

PMID:
23137963
PMCID:
PMC3555889
DOI:
10.4161/gmic.22596
[Indexed for MEDLINE]
Free PMC Article

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