Evidence map›Paper›PMID 26458401›Full record

ArticleMalaria journal2015

Characterization and optimization of the haemozoin-like crystal (HLC) assay to determine Hz inhibiting effects of anti-malarial compounds.

Carolina Tempera, Ricardo Franco, Carlos Caro, Vânia André, Peter Eaton, Peter Burke, Thomas Hänscheid

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 15 citations in OpenAlex.

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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

7 authors at 6 institutions in 3 countries.

Carolina TemperaFaculdade de Medicina de Lisboa, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal. ctempera@fm.ul.pt.
Ricardo FrancoDepartamento de Química, Faculdade de Ciências e Tecnologia, UCIBIO, REQUIMTE, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. ricardo.franco@fct.unl.pt.
Carlos CaroDepartamento de Química, Faculdade de Ciências e Tecnologia, UCIBIO, REQUIMTE, Universidade NOVA de Lisboa, 2829-516, Caparica, Portugal. cacarsal@gmail.com.
Vânia AndréCentro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisbon, Portugal. vaniandre@tecnico.ulisboa.pt.
Peter Eaton, Departamento de Química e Bioquímica, Faculdade de Ciências, REQUIMTE/UCIBIO, Universidade do Porto, 4169-007, Porto, Portugal. peter.eaton@fc.up.pt.
Peter BurkeSTERIS Corporation, 5960 Heisley Road, Mentor, OH, 44060, USA. Peter_Burke@steris.com.
Thomas HänscheidFaculdade de Medicina de Lisboa, Instituto de Medicina Molecular, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal. t.hanscheid@fm.ul.pt.
Rede de Química e Tecnologia · PTInstituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento · PTInstituto de Medicina Tropical · PYSteris (United States) · USUniversidade do Porto · PTUniversity of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe haem-haemozoin biocrystallization pathway is an attractive target where several efficacious and safe anti-malarial drugs act. Consequently, in vitro haemozoin (Hz) inhibition assays have been developed to identify novel compounds. However, results may differ between assays and often require complex methods or sophisticated infrastructure. The recently reported growth of haemozoin-like crystals (HLC) appears to be a simple alternative although the endproduct is structurally different to Hz. This study set out to characterize this assay in depth, optimize it, and assess its performance.

methodsThe HLC assay was used as previously described but a range of different growth conditions were examined. Obtained HLCs were investigated and compared to synthetic (sHz) and natural haemozoin (nHz) using scanning electron microscopy, powder X-ray diffraction (PXRD), Fourier Transform Infrared spectroscopy (FTIR) and Raman spectroscopy (RS). Interactions of HLC with quinolines was analysed using RS. Inhibitory effects of currently used anti-malarial drugs under four final growth conditions were established.

resultsHLC growth requires Mycoplasma Broth Base, Tween 80, pancreatin, and lysed blood or haemin. HLCs are similar to nHz and sHz in terms of solubility, macroscopic and microscopic appearance although PXRD, FTIR and RS confirm that the haem aggregates of HLCs are structurally different. RS reveals that CQ seems to interact with HLCs in similar ways as with Hz. Inhibition of quinoline drugs ranged from 62.5 µM (chloroquine, amodiaquine, piperaquine) to 500 µM in mefloquine.

conclusionsThe HLC assay provides data on inhibiting properties of compounds. Even if the end-product is not structurally identical to Hz, the inhibitory effects appear consistent with those obtained with sHz assays, as illustrated by the results obtained for quinolines. The assay is simple, inexpensive, robust, reproducible and can be performed under basic laboratory conditions with a simple visual positive/negative read-out.

Indexed as

AntimalarialsHemeproteinsHumansMicroscopy, Electron, ScanningProtein BindingQuinolinesSpectroscopy, Fourier Transform InfraredSpectrum Analysis, RamanX-Ray DiffractionAntimalarialsHemeproteinshemozoinQuinolines

Identifiers

PMID26458401
PMCPMC4603294
OpenAlexW1923702268

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.