Summary of Study ST001033
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000691. The data can be accessed directly via it's Project DOI: 10.21228/M8C10N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001033 |
| Study Title | Determination of mode of action of anti-malalrial drugs using untargeted metabolomics |
| Study Summary | 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. |
| Institute | Monash University |
| Last Name | Creek |
| First Name | Darren |
| Address | Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Melbourne, Victoria, 3052, Australia |
| darren.creek@monash.edu | |
| Phone | +61 (0) 3 9903 9249 |
| Submit Date | 2018-08-13 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2018-08-27 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO001066 |
| Collection Summary: | Plasmodium falciparum (3D7 strain) parasites were cultured in vitro according to the established method (Trager and Jensen 1976, DOI: 10.1126/science.781840) with minor modifications and incubated with test compounds as previously described (Creek et al 2016, DOI: 10.1128/AAC.01226-16). Briefly, parasites were brought to a tightly synchronous life stage population (within 4 hours of the 48 hour life cycle) by treating with 5% (w/v) sorbitol twice at an interval of 14 hours, and incubated for a further 58 hours to bring all parasites to mid-trophozoite stage (27-31 hours post infection). These cells were used for drug treatment and further analysis. |
| Sample Type: | Cultured cells |
