Summary of Study ST000414

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 PR000323. The data can be accessed directly via it's Project DOI: 10.21228/M8ZS3N This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST000414
Study TitleMetabolomics-based screening of the Malaria Box reveals both novel and established mechanisms of action
Study TypeDrug incubation
Study SummaryMeasuring the impact of MMV Malaria Box compounds on metabolism in Plasmodium falciparum-infected red blood cells
Institute
Monash Institute of Pharmaceutical Sciences
DepartmentDrug delivery, disposition and dynamics
LaboratoryCreek lab
Last NameCreek
First NameDarren
Address381 Royal Parade, Parkville, Melbourne, VIC3052, Australia
EmailDarren.Creek@monash.edu
PhoneN/A
Submit Date2016-06-16
Num Groups126
Total Subjects18
Study Comments524
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2017-07-10
Release Version1
Darren Creek Darren Creek
https://dx.doi.org/10.21228/M8ZS3N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000323
Project DOI:doi: 10.21228/M8ZS3N
Project Title:Metabolomics-based screening of the Malaria Box reveals both novel and established mechanisms of action
Project Summary:Metabolomics-based screening of the Malaria Box reveals both novel and established mechanisms of action
Institute:Monash University
Department:Monash Institute of Pharmaceutical Sciences, Drug Delivery, Disposition and Dynamics
Laboratory:Creek lab
Last Name:Creek
First Name:Darren
Address:381 Royal Parade, Parkville, Melbourne, VIC3052, Australia
Email:Darren.Creek@monash.edu
Phone:not provided
Funding Source:NHMRC

Subject:

Subject ID:SU000435
Subject Type:Cells
Subject Species:Plasmodium falciparum
Taxonomy ID:5833
Genotype Strain:3D7
Species Group:Microorganism

Factors:

Subject type: Cells; Subject species: Plasmodium falciparum (Factor headings shown in green)

mb_sample_id local_sample_id Drug
SA020320ciDGb2-deoxyglucose
SA020321ciDGa2-deoxyglucose
SA020322ciDGc2-deoxyglucose
SA020323ciDGd2-deoxyglucose
SA020324ciArt0010bArt0010
SA020325ciArt0010aArt0010
SA020326ciArt0010dArt0010
SA020327ciArt0010cArt0010
SA020328ciArt0100cArt0100
SA020329ciArt0100bArt0100
SA020330ciArt0100dArt0100
SA020331ciArt0100aArt0100
SA020332ciArt1000aArt1000
SA020333ciArt1000dArt1000
SA020334ciArt1000cArt1000
SA020335ciArt1000bArt1000
SA020336ciARdArtemisinin
SA020337ciARcArtemisinin
SA020338ciArtemisbArtemisinin
SA020339ciARbArtemisinin
SA020340ciArtemisaArtemisinin
SA020341ciArtemiscArtemisinin
SA020342ciARaArtemisinin
SA020343ciArtemisdArtemisinin
SA020344ciAtovaqndAtovaqn
SA020345ciAtovaqncAtovaqn
SA020346ciAtovaqnbAtovaqn
SA020347ciAtovaqnaAtovaqn
SA020348ciAQaAtovaquone
SA020349ciAQbAtovaquone
SA020350ciAQdAtovaquone
SA020351ciAQcAtovaquone
SA020352Blank3Blank
SA020353Blank2Blank
SA020354blank1Blank
SA020355BlankrestartBlank
SA020356Blank1_140319142833Blank
SA020357BMSolventdBlank
SA020358blankstartBlank
SA020359BMSolventb_140311064719Blank
SA020360bMSolventcBlank
SA020361bMSolventbBlank
SA020362bMSolventBlank
SA020363BMSolventbBlank
SA020364ciBSbButhionine Sulfoxime
SA020365ciBScButhionine Sulfoxime
SA020366ciBSdButhionine Sulfoxime
SA020367ciBSaButhionine Sulfoxime
SA020808ci33bc3361
SA020809ci33dc3361
SA020810ci33cc3361
SA020811ci33ac3361
SA020368ciCQcChloroquine
SA020369ciCQdChloroquine
SA020370ciCQbChloroquine
SA020371ciCQaChloroquine
SA020372ciDMbDMSO_DF
SA020373ciDMaDMSO_DF
SA020374ciDMcDMSO_DF
SA020375ciDMSO_DFfDMSO_DF
SA020376ciDMSO_DFhDMSO_DF
SA020377ciDMSO_DFaDMSO_DF
SA020378ciDMdDMSO_DF
SA020379ciDMSO_DFcDMSO_DF
SA020380ciDMSO_DFbDMSO_DF
SA020381ciDMSO_DFdDMSO_DF
SA020382ciDMSO_DFeDMSO_DF
SA020383ciDMSO_DFgDMSO_DF
SA020384ciFAaFluoroacetate
SA020385ciFAdFluoroacetate
SA020386ciFAbFluoroacetate
SA020387ciFAcFluoroacetate
SA020388ciMB1_A02dMB1_A02
SA020389ciMB1_A02aMB1_A02
SA020390ciMB1_A02bMB1_A02
SA020391ciMB1_A02cMB1_A02
SA020392ciMB1_A03cMB1_A03
SA020393ciMB1_A03bMB1_A03
SA020394ciMB1_A03aMB1_A03
SA020395ciMB1_A03dMB1_A03
SA020396ciMB1_A04aMB1_A04
SA020397ciMB1_A04cMB1_A04
SA020398ciMB1_A04bMB1_A04
SA020399ciMB1_A04dMB1_A04
SA020400ciMB1_A05bMB1_A05
SA020401ciMB1_A05dMB1_A05
SA020402ciMB1_A05aMB1_A05
SA020403ciMB1_A05cMB1_A05
SA020404ciMB1_A06cMB1_A06
SA020405ciMB1_A06aMB1_A06
SA020406ciMB1_A06dMB1_A06
SA020407ciMB1_A06bMB1_A06
SA020408ciMB1_A07bMB1_A07
SA020409ciMB1_A07dMB1_A07
SA020410ciMB1_A07cMB1_A07
SA020411ciMB1_A07aMB1_A07
SA020412ciMB1_A08cMB1_A08
SA020413ciMB1_A08dMB1_A08
SA020414ciMB1_A08aMB1_A08
SA020415ciMB1_A08bMB1_A08
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Collection:

Collection ID:CO000429
Collection Summary:Asexual P. falciparum (3D7) were cultured with minor modifications to the method of Trager and Jensen using human RBC (Australian Red Cross Blood Service) at 3% hematocrit in modified RPMI medium containing hypoxanthine and 0.5% (w/v) albumax at 37 °C under defined atmosphere (95% N2, 4% CO2, 1% O2). Parasites were synchronized with 5% (w/v) sorbitol twice at an interval of 14 hours and cultured for a further 58 hours to ensure all experiments were performed on mid-trophozoite stage cultures (~30 h post infection) at 7-8% parasitaemia.
Sample Type:Cell

Treatment:

Treatment ID:TR000449
Treatment Summary:Cultures (200 µL) were incubated with test compounds (1 µM) for 5 hours in 96-well plates. Four replicate incubations of each compound were conducted and analyzed. Untreated controls contained equivalent amounts of DMSO (as vehicle), and additional ‘quench test’ controls were prepared whereby the test compounds were added after the quenching step, to allow detection of test compound-derived LC-MS features that did not arise from biochemical metabolism within the cells. Each plate contained 10 or 20 test compounds in addition to positive controls (artemisinin and/or atovaquone) and negative controls (untreated DMSO and ‘quench test’ described above). Incubations and extractions for the 100 test compounds (10 compounds with known antimalarial activity and 90 of the highest priority compounds from the Malaria Box including all of plate A and the first row of plate B) were performed in three separate batches, with the known antimalarial compounds and first 10 Malaria Box compounds in the first batch, the next 40 Malaria Box compounds in the second batch, and the following 40 Malaria Box compounds in the third batch.
Treatment Compound:Antimalarials and MMV Malaria Box compounds
Treatment Dose:1 micromolar
Treatment Doseduration:5 hours
Treatment Vehicle:DMSO
Cell Growth Container:96-well V-bottomed plate
Cell Media:RPMI-HEPES
Cell Envir Cond:37 °C under defined atmosphere (95% N2, 4% CO2, 1% O2)
Cell Media Lastchanged:18 hours

Sample Preparation:

Sampleprep ID:SP000442
Sampleprep Summary:Culture medium was removed by aspiration, and the metabolism of the settled iRBCs quenched by addition of ice-cold phosphate buffered saline (PBS). Subsequent steps were performed on ice. Cells were pelleted by centrifugation for 5 min at 1000 × g and the PBS supernatant removed prior to the addition of 135 µL methanol (containing internal standard compounds: CHAPS, CAPS and PIPES) and rapid mixing by pipetting three times to extract iRBC metabolites. Samples were left on ice with gentle agitation for 60 minutes, then centrifuged at 3000 × g to remove the insoluble material. Supernatants were transferred to glass HPLC vials and stored (< 4 months) at -80 °C until analysis.
Processing Method:Lysis with organic solvent and mixing at 4°C
Processing Storage Conditions:on ice or 4°C
Extraction Method:Methanol (10:1)
Extract Storage:-80°C
Sample Spiking:internal standards (CHAPS, CAPS, PIPES all at 1 µM) mixed in extraction solvent
Cell Type:Plasmodium falciparum-infected red blood cells (8% parasitaemia and 3% haematocrit

Combined analysis:

Analysis ID AN000655 AN000656
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Dionex Ultimate 3000 RS Thermo Dionex Ultimate 3000 RS
Column ZIC-pHILIC (Merck Sequant) ZIC-pHILIC (Merck Sequant)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units peak height Peak height

Chromatography:

Chromatography ID:CH000473
Chromatography Summary:Untargeted HILIC method
Methods Filename:pHILIC_32min_posneg_71114.meth
Instrument Name:Thermo Dionex Ultimate 3000 RS
Column Name:ZIC-pHILIC (Merck Sequant)
Column Temperature:25°C
Flow Gradient:linear gradient -time, %B as follows: 0min- 80%, 15min- 50%, 18min- 5%, 21min- 5%, 24min- 80%, 32min- 80%.
Flow Rate:300 μL/min
Injection Temperature:4 °C
Internal Standard:internal standards (CHAPS, CAPS, PIPES; all at 1 µM)
Sample Injection:10 μL
Solvent A:100% water; 20 mM ammonium carbonate
Solvent B:100% acetonitrile
Chromatography Type:HILIC

MS:

MS ID:MS000581
Analysis ID:AN000655
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
Ion Mode:POSITIVE
Capillary Temperature:300°C
Capillary Voltage:+50V
Dry Gas Flow:20
Fragmentation Method:None
Ion Spray Voltage:3.5kV
Desolvation Gas Flow:50
Desolvation Temperature:150°C
Resolution Setting:35000
Scan Range Moverz:85- 1275 m/z
  
MS ID:MS000582
Analysis ID:AN000656
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
Ion Mode:NEGATIVE
Capillary Temperature:300°C
Capillary Voltage:-50V
Dry Gas Flow:20
Fragmentation Method:None
Ion Spray Voltage:3.5kV
Desolvation Gas Flow:50
Desolvation Temperature:150°C
Resolution Setting:35000
Scan Range Moverz:85- 1275 m/z
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