Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications

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Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications. / Ch'ng, Jun Hong; Moll, Kirsten; Quintana, Maria Del Pilar; Chan, Sherwin Chun Leung; Masters, Ellen; Moles, Ernest; Liu, Jianping; Eriksson, Anders B.; Wahlgren, Mats.

In: Scientific Reports, Vol. 6, 29317, 11.07.2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ch'ng, JH, Moll, K, Quintana, MDP, Chan, SCL, Masters, E, Moles, E, Liu, J, Eriksson, AB & Wahlgren, M 2016, 'Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications', Scientific Reports, vol. 6, 29317. https://doi.org/10.1038/srep29317

APA

Ch'ng, J. H., Moll, K., Quintana, M. D. P., Chan, S. C. L., Masters, E., Moles, E., Liu, J., Eriksson, A. B., & Wahlgren, M. (2016). Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications. Scientific Reports, 6, [29317]. https://doi.org/10.1038/srep29317

Vancouver

Ch'ng JH, Moll K, Quintana MDP, Chan SCL, Masters E, Moles E et al. Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications. Scientific Reports. 2016 Jul 11;6. 29317. https://doi.org/10.1038/srep29317

Author

Ch'ng, Jun Hong ; Moll, Kirsten ; Quintana, Maria Del Pilar ; Chan, Sherwin Chun Leung ; Masters, Ellen ; Moles, Ernest ; Liu, Jianping ; Eriksson, Anders B. ; Wahlgren, Mats. / Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications. In: Scientific Reports. 2016 ; Vol. 6.

Bibtex

@article{4ef34524560d4e62aceb8d4ef215cfd3,
title = "Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications",
abstract = "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.",
author = "Ch'ng, {Jun Hong} and Kirsten Moll and Quintana, {Maria Del Pilar} and Chan, {Sherwin Chun Leung} and Ellen Masters and Ernest Moles and Jianping Liu and Eriksson, {Anders B.} and Mats Wahlgren",
year = "2016",
month = jul,
day = "11",
doi = "10.1038/srep29317",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications

AU - Ch'ng, Jun Hong

AU - Moll, Kirsten

AU - Quintana, Maria Del Pilar

AU - Chan, Sherwin Chun Leung

AU - Masters, Ellen

AU - Moles, Ernest

AU - Liu, Jianping

AU - Eriksson, Anders B.

AU - Wahlgren, Mats

PY - 2016/7/11

Y1 - 2016/7/11

N2 - 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.

AB - 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.

U2 - 10.1038/srep29317

DO - 10.1038/srep29317

M3 - Journal article

AN - SCOPUS:84978381260

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 29317

ER -

ID: 197729246