Metabolomics-Based Screening of the Malaria Box Reveals both Novel and Established Mechanisms of Action.

ABSTRACT: 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. Select Malaria Box compounds also induced changes in intermediates in essential metabolic pathways, such

SUBMITTER: Creek DJ 

PROVIDER: S-EPMC5075070 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature