10.4225/03/57A80CE1503CD
Darren Creek
Darren
Creek
Malaria Box Metabolomics LCMS
Monash University
2016
metabolomics studies
Malaria
antimalarials
Malaria Box
Plasmodium falciparum
Analytical Biochemistry
Parasitology
Pharmacology
Systems Biology
Infectious Diseases
2016-08-08 04:38:55
Dataset
https://bridges.monash.edu/articles/dataset/Malaria_Box_Metabolomics_LCMS/3545681
<p>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
remain 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 <i>in vitro </i>cultures of <i>P. falciparum</i>.
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 as isoprenoid biosynthesis (i.e. 2-C-methyl-D-erythritol
2,4-cyclodiphosphate), and linolenic acid metabolism (i.e. traumatic acid). This
study provides a comprehensive database of the metabolic perturbations induced
by chemically diverse inhibitors and highlights the utility of metabolomics for
triaging new lead compounds and defining specific modes of action, which will
assist with the development and optimization of new antimalarial drugs. </p>