Evidence map›Paper›PMID 30082744›Full record

ArticleScientific reports2018

Importance of secondary screening with clinical isolates for anti-leishmania drug discovery.

Aya Hefnawy, Juan Cantizani, Imanol Peña, Pilar Manzano, Suman Rijal, Jean-Claude Dujardin, Geraldine De Muylder, Julio Martin

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 31 citations in OpenAlex.

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  8. Towards discovery of new leishmanicidal scaffolds able to inhibitJournal of enzyme inhibition and medicinal chemistry · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 4 countries.

Aya HefnawyDepartment of Biomedical sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Juan CantizaniDiseases of the developing world, GlaxoSmithKline, Tres cantos, Spain.
Imanol PeñaDiseases of the developing world, GlaxoSmithKline, Tres cantos, Spain.
Pilar ManzanoDiseases of the developing world, GlaxoSmithKline, Tres cantos, Spain.
Suman RijalBP Koirala Institute of Health Sciences, Dharan, Nepal.
Jean-Claude DujardinDepartment of Biomedical sciences, Institute of Tropical Medicine, Antwerp, Belgium. JCDujardin@itg.be.
Geraldine De MuylderDepartment of Biomedical sciences, Institute of Tropical Medicine, Antwerp, Belgium.ORCID 0000-0003-2295-5564
Julio MartinDiseases of the developing world, GlaxoSmithKline, Tres cantos, Spain. Julio.J.Martin@gsk.com.
GlaxoSmithKline (Spain) · ESInstituut voor Tropische Geneeskunde · BEB.P. Koirala Institute of Health Sciences · NPGlaxoSmithKline (France) · FRUniversity of Antwerp · BE

Funding

EC | Horizon 2020 (European Union Framework Programme for Research and Innovation) 642609Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders) 12Q8115N
6 · The paper itself

Abstract

The growing drug resistance (DR) raises major concerns for the control of visceral leishmaniasis (VL), a neglected disease lethal in 95 percent of the cases if left untreated. Resistance has rendered antimonials (SSG) obsolete in the Indian Sub-Continent (ISC) and the first miltefosine-resistant Leishmania donovani were isolated. New chemotherapeutic options are needed and novel compounds are being identified by high-throughput screening (HTS). HTS is generally performed with old laboratory strains such as LdBOB and we aimed here to validate the activity of selected compounds against recent clinical isolates. In this academic/industrial collaboration, 130 compounds from the GSK "Leishbox" were screened against one SSG-sensitive and one SSG-resistant strain of L. donovani recently isolated from ISC patients, using an intracellular assay of L. donovani-infected THP1-derived macrophages. We showed that only 45% of the compounds were active in both clinical isolates and LdBOB. There were also different compound efficiencies linked to the SSG susceptibility background of the strains. In addition, our results suggested that the differential susceptibility profiles were chemical series-dependent. In conclusion, we demonstrate the potential value of including clinical isolates (as well as resistant strains) in the HTS progression cascade.

Indexed as

Antiprotozoal AgentsDrug DiscoveryDrug ResistanceHumansLeishmania donovaniLeishmaniasis, VisceralMacrophagesPhosphorylcholineTHP-1 CellsAntiprotozoal AgentsmiltefosinePhosphorylcholine

Identifiers

PMID30082744
PMCPMC6078976
OpenAlexW2886065450

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.