Journal article

Comparison of the Exposure Time Dependence of the Activities of Synthetic Ozonide Antimalarials and Dihydroartemisinin against K13 Wild-Type and Mutant Plasmodium falciparum Strains

Tuo Yang, Stanley C Xie, Pengxing Cao, Carlo Giannangelo, James McCaw, Darren J Creek, Susan A Charman, Nectarios Klonis, Leann Tilley

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | AMER SOC MICROBIOLOGY | Published : 2016

Abstract

Fully synthetic endoperoxide antimalarials, namely, OZ277 (RBx11160; also known as arterolane) and OZ439 (artefenomel), have been approved for marketing or are currently in clinical development. We undertook an analysis of the kinetics of the in vitro responses of Plasmodium falciparum to the new ozonide antimalarials. For these studies we used a K13 mutant (artemisinin resistant) isolate from a region in Cambodia and a genetically matched (artemisinin sensitive) K13 revertant. We used a pulsed-exposure assay format to interrogate the time dependence of the response. Because the ozonides have physicochemical properties different from those of the artemisinins, assay optimization was required..

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Grants

Awarded by Department of Health \ National Health and Medical Research Council (NHMRC)


Awarded by Australian Research Council (ARC)


Funding Acknowledgements

This work, including the efforts of Leann Tilley, was funded by Department of Health vertical bar National Health and Medical Research Council (NHMRC) (APP1092808). This work, including the efforts of Leann Tilley, was funded by Department of Health vertical bar National Health and Medical Research Council (NHMRC) (APP1060357). This work, including the efforts of Leann Tilley, was funded by Australian Research Council (ARC) (DP110100624).