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  • Identification of inhibitors of Plasmodium falciparum gametocyte development

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    Author(s)
    Duffy, Sandra
    Avery, Vicky M
    Griffith University Author(s)
    Duffy, Sandra
    Avery, Vicky M.
    Year published
    2013
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    Abstract
    BACKGROUND: Plasmodium falciparum gametocytes, specifically mature stages, are the only stage in man transmissible to the mosquito vector responsible for malaria transmission. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria. The comprehensive profiling of in vitro activity of anti-malarial compounds against both early (I-III) and late (IV-V) stage P. falciparum gametocytes, along with the high throughput screening (HTS) outcomes from the MMV malaria box are described. METHOD: Two anti-gametocyte HTS assays based on confocal fluorescence microscopy, utilizing both a ...
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    BACKGROUND: Plasmodium falciparum gametocytes, specifically mature stages, are the only stage in man transmissible to the mosquito vector responsible for malaria transmission. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria. The comprehensive profiling of in vitro activity of anti-malarial compounds against both early (I-III) and late (IV-V) stage P. falciparum gametocytes, along with the high throughput screening (HTS) outcomes from the MMV malaria box are described. METHOD: Two anti-gametocyte HTS assays based on confocal fluorescence microscopy, utilizing both a gametocyte specific protein (pfs16-GFP) and a viability marker (MitoTracker Red CM-H2XRos)(MTR), were used for the measurement of anti-gametocytocidal activity. This combination provided a direct observation of gametocyte number per assay well, whilst defining the viability of each gametocyte imaged. RESULTS: IC50 values were obtained for 36 current anti-malarial compounds for activities against asexual, early and late stage gametocytes. The MMV malaria box was screened and actives progressed for IC50 evaluation. Seven % of the "drug-like" and 21% of the "probe-like" compounds from the MMV malaria box demonstrated equivalent activity against both asexual and late stage gametocytes. CONCLUSIONS: The assays described were shown to selectively identify compounds with gametocytocidal activity and have been demonstrated suitable for HTS with the capability of screening in the order of 20,000 compounds per screening campaign, two to three times per seven-day week.
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    Journal Title
    Malaria Journal
    Volume
    12
    DOI
    https://doi.org/10.1186/1475-2875-12-408
    Copyright Statement
    © 2013 Duffy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Note
    Page numbers are not for citation purposes. Instead, this article has the unique article number of 408.
    Subject
    Medicinal and biomolecular chemistry not elsewhere classified
    Microbiology
    Medical microbiology
    Public health
    Publication URI
    http://hdl.handle.net/10072/56600
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    • Journal articles

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