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Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites

Overview of attention for article published in International Journal of Parasitology: Drugs and Drug Resistance, June 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Good Attention Score compared to outputs of the same age and source (70th percentile)

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Citations

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Title
Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against Plasmodium and Trypanosoma parasites
Published in
International Journal of Parasitology: Drugs and Drug Resistance, June 2015
DOI 10.1016/j.ijpddr.2015.05.004
Pubmed ID
Authors

Jessica A. Engel, Amy J. Jones, Vicky M. Avery, Subathdrage D.M. Sumanadasa, Susanna S. Ng, David P. Fairlie, Tina S. Adams, Katherine T. Andrews

Abstract

Histone deacetylase (HDAC) enzymes work together with histone acetyltransferases (HATs) to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug targets for some types of cancer, with four HDAC inhibitors clinically approved. However, they are also showing promise as novel drug targets for other indications, including malaria and other parasitic diseases. In this study the in vitro activity of four anti-cancer HDAC inhibitors was examined against parasites that cause malaria and trypanosomiasis. Three of these inhibitors, suberoylanilide hydroxamic acid (SAHA; vorinostat(®)), romidepsin (Istodax(®)) and belinostat (Beleodaq(®)), are clinically approved for the treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been approved for combination therapy use in certain patients with multiple myeloma. All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium falciparum malaria parasites in the nanomolar range (IC50 10-200 nM), while only romidepsin was active at sub-μM concentrations against bloodstream form Trypanosoma brucei brucei parasites (IC50 35 nM). The compounds were found to have some selectivity for malaria parasites compared with mammalian cells, but were not selective for trypanosome parasites versus mammalian cells. All compounds caused hyperacetylation of histone and non-histone proteins in P. falciparum asexual stage parasites and inhibited deacetylase activity in P. falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P. falciparum histone hyperacetylation data indicate that HDAC inhibitors may differentially affect the acetylation profiles of histone H3 and H4.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Argentina 1 <1%
Unknown 107 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 22 20%
Student > Master 19 18%
Researcher 17 16%
Student > Bachelor 13 12%
Student > Doctoral Student 7 6%
Other 16 15%
Unknown 14 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 25 23%
Chemistry 21 19%
Agricultural and Biological Sciences 15 14%
Medicine and Dentistry 8 7%
Pharmacology, Toxicology and Pharmaceutical Science 6 6%
Other 14 13%
Unknown 19 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 01 January 2016.
All research outputs
#7,968,106
of 25,394,764 outputs
Outputs from International Journal of Parasitology: Drugs and Drug Resistance
#136
of 407 outputs
Outputs of similar age
#86,926
of 278,651 outputs
Outputs of similar age from International Journal of Parasitology: Drugs and Drug Resistance
#3
of 10 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 407 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one has gotten more attention than average, scoring higher than 64% 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 278,651 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 67% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 7 of them.