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High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis

Overview of attention for article published in Infectious Diseases of Poverty, August 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (65th percentile)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

Mentioned by

twitter
6 tweeters

Citations

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21 Dimensions

Readers on

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34 Mendeley
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Title
High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis
Published in
Infectious Diseases of Poverty, August 2015
DOI 10.1186/s40249-015-0071-z
Pubmed ID
Authors

Ting Li, Peter D. Ziniel, Pan-qing He, Valerie P. Kommer, Gregory J. Crowther, Min He, Qing Liu, Wesley C. Van Voorhis, David L. Williams, Ming-Wei Wang

Abstract

Schistosomiasis, a parasitic disease also known as bilharzia and snail fever, is caused by different species of flatworms, such as Schistosoma mansoni (S. mansoni). Thioredoxin glutathione reductase (TGR) from S. mansoni (SmTGR) is a well-characterized drug target for schistosomiasis, yet no anti-SmTGR compounds have reached clinical trials, suggesting that therapeutic development against schistosomiasis might benefit from additional scaffolds targeting this enzyme. A high-throughput screening (HTS) assay in vitro against SmTGR was developed and applied to a diverse compound library. SmTGR activity was quantified with ThioGlo®, a reagent that fluoresces upon binding to the free sulfhydryl groups of the reaction product GSH (reduced glutathione). We implemented an HTS effort against 59,360 synthetic compounds. In the primary screening, initial hits (928 or 1.56 %) showing greater than 90 % inhibition on SmTGR activity at a final concentration of 10 μM for each compound were identified. Further tests were carried out to confirm the effects of these hits and to explore the concentration-dependent response characteristics. As a result, 74 of them (0.12 %) representing 17 chemical scaffolds were confirmed and showed a great concentration-dependent inhibitory trend against SmTGR, including structures previously shown to be lethal to schistosomal growth. Of these, two scaffolds displayed a limited structure-activity relationship. When tested in cultured larvae, 39 compounds had cidal activity in 48 h, and five of them killed larvae completely at 3.125 μM. Of these, three compounds also killed adult worms ex vivo at concentrations between 5 μM and 10 μM. These confirmed hits may serve as starting points for the development of novel therapeutics to combat schistosomiasis.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 3 9%
Malaysia 1 3%
Unknown 30 88%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 21%
Professor > Associate Professor 3 9%
Student > Ph. D. Student 3 9%
Student > Doctoral Student 3 9%
Researcher 3 9%
Other 7 21%
Unknown 8 24%
Readers by discipline Count As %
Chemistry 7 21%
Agricultural and Biological Sciences 7 21%
Medicine and Dentistry 4 12%
Biochemistry, Genetics and Molecular Biology 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Other 4 12%
Unknown 7 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 April 2016.
All research outputs
#2,936,855
of 7,520,778 outputs
Outputs from Infectious Diseases of Poverty
#96
of 257 outputs
Outputs of similar age
#75,558
of 228,871 outputs
Outputs of similar age from Infectious Diseases of Poverty
#3
of 9 outputs
Altmetric has tracked 7,520,778 research outputs across all sources so far. This one has received more attention than most of these and is in the 60th percentile.
So far Altmetric has tracked 257 research outputs from this source. They receive a mean Attention Score of 3.9. This one has gotten more attention than average, scoring higher than 61% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 228,871 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 6 of them.