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Open Access 01-12-2018 | Research

Profiling of the anti-malarial drug candidate SC83288 against artemisinins in Plasmodium falciparum

Authors: Maëlle Duffey, Cecilia P. Sanchez, Michael Lanzer

Published in: Malaria Journal | Issue 1/2018

Abstract

Background

The increased resistance of the human malaria parasite Plasmodium falciparum to currently employed drugs creates an urgent call for novel anti-malarial drugs. Particularly, efforts should be devoted to developing fast-acting anti-malarial compounds in case clinical resistance increases to the first-line artemisinin-based combination therapy. SC83288, an amicarbalide derivative, is a clinical development candidate for the treatment of severe malaria. SC83288 is fast-acting and able to clear P. falciparum parasites at low nanomolar concentrations in vitro, as well as in a humanized SCID mouse model system in vivo. In this study, the antiplasmodial activity of SC83288 against artemisinins was profiled in order to assess its potential to replace, or be combined with, artemisinin derivatives.

Results

Based on growth inhibition and ring survival assays, no cross-resistance was observed between artemisinins and SC83288, using parasite lines that were resistant to either one of these drugs. In addition, no synergistic or antagonistic interaction was observed between the two drugs. This study further confirmed that SC83288 is a fast acting drug in several independent assays. Combinations of SC83288 and artesunate maintained the rapid parasite killing activities of both components.

Conclusion

The results obtained in this study are consistent with artemisinins and SC83288 having distinct modes of action and different mechanisms of resistance. This study further supports efforts to continue the clinical development of SC83288 against severe malaria as an alternative to artemisinins in areas critically affected by artemisinin-resistance. Considering its fast antiplasmodial activity, SC83288 could be combined with a slow-acting anti-malarial drug.

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Title: Profiling of the anti-malarial drug candidate SC83288 against artemisinins in Plasmodium falciparum
Authors: Maëlle Duffey
Cecilia P. Sanchez
Michael Lanzer
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI: https://doi.org/10.1186/s12936-018-2279-4

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Profiling of the anti-malarial drug candidate SC83288 against artemisinins in Plasmodium falciparum

Abstract

Background

Results

Conclusion

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Abstract

Background

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Conclusion

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