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Diversity-oriented natural product platform identifies plant constituents targeting Plasmodium falciparum

Overview of attention for article published in Malaria Journal, May 2016
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (54th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (52nd percentile)

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Title
Diversity-oriented natural product platform identifies plant constituents targeting Plasmodium falciparum
Published in
Malaria Journal, May 2016
DOI 10.1186/s12936-016-1313-7
Pubmed ID
Authors

Jin Zhang, John J. Bowling, David Smithson, Julie Clark, Melissa R. Jacob, Shabana I. Khan, Babu L. Tekwani, Michele Connelly, Vladimir Samoylenko, Mohamed A. Ibrahim, Mohamed A. Zaki, Mei Wang, John P. Hester, Ying Tu, Cynthia Jeffries, Nathaniel Twarog, Anang A. Shelat, Larry A. Walker, Ilias Muhammad, R. Kiplin Guy

Abstract

A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using an in vitro anti-malarial screening platform to identify known or new natural products for lead development. The platform identifies hits on the basis of in vitro growth inhibition of Plasmodium falciparum and counter-screens for cytotoxicity to human foreskin fibroblast or embryonic kidney cell lines. The physical library was supplemented by early-stage collection of analytical data for each fraction to aid rapid identification of the active components within each screening hit. A total of 16,177 fractions from 1300 plants were screened, identifying several P. falciparum inhibitory fractions from 35 plants. Although individual fractions were screened for bioactivity to ensure adequate signal in the analytical characterizations, fractions containing less than 2.0 mg of dry weight were combined to produce combined fractions (COMBIs). Fractions of active COMBIs had EC50 values of 0.21-50.28 and 0.08-20.04 µg/mL against chloroquine-sensitive and -resistant strains, respectively. In Berberis thunbergii, eight known alkaloids were dereplicated quickly from its COMBIs, but berberine was the most-active constituent against P. falciparum. The triterpenoids α-betulinic acid and β-betulinic acid of Eugenia rigida were also isolated as hits. Validation of the anti-malarial discovery platform was confirmed by these scaled isolations from B. thunbergii and E. rigida. These results demonstrate the value of curating and exploring a library of natural products for small molecule drug discovery. Attention given to the diversity of plant species represented in the library, focus on practical analytical data collection, and the use of counter-screens all facilitate the identification of anti-malarial compounds for lead development or new tools for chemical biology.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 20 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 20%
Student > Ph. D. Student 3 15%
Student > Postgraduate 2 10%
Professor > Associate Professor 2 10%
Lecturer 1 5%
Other 4 20%
Unknown 4 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 15%
Chemistry 3 15%
Medicine and Dentistry 2 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Social Sciences 1 5%
Other 3 15%
Unknown 7 35%
Attention Score in Context

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 03 October 2016.
All research outputs
#12,761,847
of 22,869,263 outputs
Outputs from Malaria Journal
#3,026
of 5,578 outputs
Outputs of similar age
#138,524
of 304,990 outputs
Outputs of similar age from Malaria Journal
#65
of 153 outputs
Altmetric has tracked 22,869,263 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,578 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
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 304,990 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 54% of its contemporaries.
We're also able to compare this research output to 153 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.