Metabolomics-Based Screening of the Malaria Box Reveals both Novel and Established Mechanisms of Action
Darren J Creek, Hwa H Chua, Simon A Cobbold, Brunda Nijagal, James I MacRae, Benjamin K Dickerman, Paul R Gilson, Stuart A Ralph, Malcolm J McConville
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2016
High-throughput phenotypic screening of chemical libraries has resulted in the identification of thousands of compounds with potent antimalarial activity, although in most cases, the mechanism(s) of action of these compounds remains unknown. Here we have investigated the mode of action of 90 antimalarial compounds derived from the Malaria Box collection using high-coverage, untargeted metabolomics analysis. Approximately half of the tested compounds induced significant metabolic perturbations in in vitro cultures of Plasmodium falciparum In most cases, the metabolic profiles were highly correlated with known antimalarials, in particular artemisinin, the 4-aminoquinolines, or atovaquone. Sele..View full abstract
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Awarded by Australian National Health and Medical Research Council
This work was funded by Australian National Health and Medical Research Council grants to Malcolm J. McConville and Stuart A. Ralph (APP106024), Darren J. Creek (APP1088855; APP), and Stuart A. Ralph (APP1062504).