Evidence map›Paper›PMID 24060871›Full record

ArticleAntimicrobial agents and chemotherapy2013

Identification of MMV malaria box inhibitors of plasmodium falciparum early-stage gametocytes using a luciferase-based high-throughput assay.

Leonardo Lucantoni, Sandra Duffy, Sophie H Adjalley, David A Fidock, Vicky M Avery

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 2 pooled it
14.0field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.

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  13. Frontiers in cellular and infection microbiology · 2022
    Article
  14. Streamlined and Robust Stage-Specific Profiling of Gametocytocidal Compounds AgainstFrontiers in cellular and infection microbiology · 2022
    Article
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7 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 2 countries.

Leonardo LucantoniDiscovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.
Sandra Duffy
Sophie H Adjalley
David A Fidock
Vicky M Avery
Griffith University · AUColumbia University Irving Medical Center · US

Funding

Pharmacologic Approaches to Combating Resistance to Antimalarial CombinationsR01AI079709 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FIDOCK, DAVID A, KYLE, DENNIS E · 2008 to 2011
$2.3M
NIAID NIH HHS R01 AI079709
6 · The paper itself

Abstract

The design of new antimalarial combinations to treat Plasmodium falciparum infections requires drugs that, in addition to resolving disease symptoms caused by asexual blood stage parasites, can also interrupt transmission to the mosquito vector. Gametocytes, which are essential for transmission, develop as sexual blood stage parasites in the human host over 8 to 12 days and are the most accessible developmental stage for transmission-blocking drugs. Considerable effort is currently being devoted to identifying compounds active against mature gametocytes. However, investigations on the drug sensitivity of developing gametocytes, as well as screening methods for identifying inhibitors of early gametocytogenesis, remain scarce. We have developed a luciferase-based high-throughput screening (HTS) assay using tightly synchronous stage I to III gametocytes from a recombinant P. falciparum line expressing green fluorescent protein (GFP)-luciferase. The assay has been used to evaluate the early-stage gametocytocidal activity of the MMV Malaria Box, a collection of 400 compounds with known antimalarial (asexual blood stage) activity. Screening this collection against early-stage (I to III) gametocytes yielded 64 gametocytocidal compounds with 50% inhibitory concentrations (IC50s) below 2.5 μM. This assay is reproducible and suitable for the screening of large compound libraries, with an average percent coefficient of variance (%CV) of ≤5%, an average signal-to-noise ratio (S:N) of >30, and a Z' of ∼0.8. Our findings highlight the need for screening efforts directed specifically against early gametocytogenesis and indicate the importance of experimental verification of early-stage gametocytocidal activity in the development of new antimalarial candidates for combination therapy.

Indexed as

Antigens, ProtozoanAntimalarialsDatabases, ChemicalErythrocytesGene ExpressionGenes, ReporterHigh-Throughput Screening AssaysHumansInhibitory Concentration 50Life Cycle StagesLuciferasesMembrane ProteinsParasitic Sensitivity TestsPlasmodium falciparumRecombinant Fusion ProteinsAntigens, ProtozoanAntimalarialsLuciferasesMembrane ProteinsPfs16 protein, Plasmodium falciparumRecombinant Fusion Proteins

Identifiers

PMID24060871
PMCPMC3837862
OpenAlexW2090344797

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.