Metabolomics

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Determination of mode of action of anti-malalrial drugs using untargeted metabolomics


ABSTRACT: The mode of action of a representative active compound was investigated using an unbiased metabolomics approach, which has previously been shown to reveal both novel and established modes of action of antimalarials (Creek et al 2016, DOI: 10.1128/AAC.01226-16). The active antimalarial OSM-S-313, and the inactive analogue OSM-S-291, were incubated with trophozoite stage P. falciparum parasites for five hours alongside reference compounds including atovaquone (ATV), chloroquine (CQ), dihydroartemisisin (DHA) and three PfATP4 inhibitors, MMV00073, MMV397264 and MMV390482. Metabolomics analysis of cell pellets and spent media allowed reproducible detection of diverse metabolites from a range of metabolic pathways, with the most significant OSM-S-313-induced perturbations observed within peptide, lipid and energy metabolism, suggesting a specific impact on parasite metabolism.

ORGANISM(S): Plasmodium Falciparum

TISSUE(S): Cultured Cells

DISEASE(S): Malaria

SUBMITTER: Darren Creek  

PROVIDER: ST001033 | MetabolomicsWorkbench | Mon Aug 13 00:00:00 BST 2018

REPOSITORIES: MetabolomicsWorkbench

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