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Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential

Overview of attention for article published in Malaria Journal, October 2019
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Title
Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential
Published in
Malaria Journal, October 2019
DOI 10.1186/s12936-019-2971-z
Pubmed ID
Authors

Sonal Gupta, Juveria Khan, Priti Kumari, Chintam Narayana, R. Ayana, Malabika Chakrabarti, Ram Sagar, Shailja Singh

Abstract

Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics. These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 17%
Student > Ph. D. Student 5 17%
Researcher 2 7%
Student > Doctoral Student 1 3%
Student > Master 1 3%
Other 3 10%
Unknown 12 41%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 17%
Agricultural and Biological Sciences 3 10%
Medicine and Dentistry 2 7%
Arts and Humanities 1 3%
Immunology and Microbiology 1 3%
Other 3 10%
Unknown 14 48%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 29 January 2020.
All research outputs
#18,032,137
of 23,168,000 outputs
Outputs from Malaria Journal
#4,908
of 5,626 outputs
Outputs of similar age
#247,791
of 353,324 outputs
Outputs of similar age from Malaria Journal
#78
of 84 outputs
Altmetric has tracked 23,168,000 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,626 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 9th percentile – i.e., 9% 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 353,324 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.