Título:
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Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the
Potential Treatment of Plasmodium falciparum Malaria
Complications
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Autor/a:
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Ch'ng, Jun-Hong; Moll, Kirsten; Quintana, Maria del Pilar; Chan, Sherwin Chun Leung; Masters, Ellen; Moles Meler, Ernest; Liu, Jianping; Eriksson, Anders B.; Wahlgren, Mats
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Abstract:
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The spread of artemisinin-resistant parasites could lead to
higher incidence of patients with malaria complications.
However, there are no current treatments that directly dislodge
sequestered parasites from the microvasculature. We show that
four common antiplasmodial drugs do not disperse rosettes
(erythrocyte clusters formed by malaria parasites) and therefore
develop a cell-based high-throughput assay to identify potential
rosette-disrupting compounds. A pilot screen of 2693 compounds
identified Malaria Box compound MMV006764 as a potential
candidate. Although it reduced rosetting by a modest 20%,
MMV006764 was validated to be similarly effective against both
blood group O and A rosettes of three laboratory parasite lines.
Coupled with its antiplasmodial activity and drug-likeness,
MMV006764 represents the first small-molecule compound that
disrupts rosetting and could potentially be used in a
resource-limited setting to treat patients deteriorating rapidly
from malaria complications. Such dual-action drugs that
simultaneously restore microcirculation and reduce parasite load
could significantly reduce malaria morbidity and mortality. |
Materia(s):
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-Plasmodium falciparum -Malària -Plasmodium falciparum -Malaria |
Derechos:
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cc by (c) Ch'ng et al., 2016
http://creativecommons.org/licenses/by/3.0/es/ |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Springer Nature
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Compartir:
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