Evidence map›Paper›PMID 24416463›Full record

ArticlePLoS neglected tropical diseases2014

Orally active antischistosomal early leads identified from the open access malaria box.

Katrin Ingram-Sieber, Noemi Cowan, Gordana Panic, Mireille Vargas, Nuha R Mansour, Quentin D Bickle, Timothy N C Wells, Thomas Spangenberg, Jennifer Keiser

Abstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
–field-weighted citation impact
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

51 citing papers in PubMed.

  1. Old drugs, new weapons: current trends in repurposing therapies against antimicrobial resistance.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
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  11. Pathogens and global health · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Antimicrobial agents and chemotherapy · 2021
    Article
  16. Diaryl Ureas as an Antiprotozoal Chemotype.ACS infectious diseases · 2021
    Article
  17. The Different Facets of Triclocarban: A Review.Molecules (Basel, Switzerland) · 2021
    Review
  18. Article
  19. Article
  20. Review
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

9 authors.

Katrin Ingram-SieberDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.
Noemi CowanDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.
Gordana PanicDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.
Mireille VargasDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.
Nuha R MansourDepartment of Infection and Immunity, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Quentin D BickleDepartment of Infection and Immunity, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Timothy N C WellsMedicines for Malaria Venture, Geneva, Switzerland.
Thomas SpangenbergMedicines for Malaria Venture, Geneva, Switzerland.
Jennifer KeiserDepartment of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland ; University of Basel, Basel, Switzerland.

Funding

Medical Research Council MR/K025430/1
6 · The paper itself

Abstract

backgroundWorldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL

findingsPromising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development.

Indexed as

Administration, OralAnimalsAnthelminticsDisease Models, AnimalFemaleInhibitory Concentration 50MiceParasite LoadParasitic Sensitivity TestsQuinoxalinesSchistosoma mansoniSchistosomiasis mansoniUreaAnthelminticsQuinoxalinesUrea

Identifiers

PMID24416463
PMCPMC3886923

What OpenQuestion holds

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Registered trials

None linked

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.