Summary of Study ST003160

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 PR001965. The data can be accessed directly via it's Project DOI: 10.21228/M8QQ8P This work is supported by NIH grant, U2C- DK119886.

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

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003160
Study TitleNew class of heterospirocyclic compounds present strong and rapid activity against artemisinin- and multidrug-resistant P. falciparum parasites
Study SummaryMalaria remains a significant health burden and a leading contributor to global mortality rates. Increasing drug resistance creates an urgent demand for novel treatment options. We have synthesised a new class of heterospirocyclic compounds with novel chemical connectivities. Compounds 25 and 26 display antimalarial activity within 24 h and have similar potency against a panel of drug-resistant strains of Plasmodium falciparum, the most virulent of human malaria parasites, including parasites resistant to the frontline artemisinin antimalarials. C25 and C26 do not induce major toxicity in kidney- and hepatic-derived human cell lines, highlighting their specificity. Untargeted metabolomics analysis of P. falciparum infected red blood cells revealed that the mechanism of action of C25 involves disruption of the pyrimidine biosynthesis pathway and haemoglobin catabolism. These heterospirocyclic compounds represent a promising opportunity for antimalarial drug development and could prove relevant against drug resistant malaria.
Institute
Monash University
Last NameGiannangelo
First NameCarlo
Address381 Royal Parade, Parkville, Victoria, 3052, Australia
Emailcarlo.giannangelo@monash.edu
Phone99039282
Submit Date2024-04-06
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-04-29
Release Version1
Carlo Giannangelo Carlo Giannangelo
https://dx.doi.org/10.21228/M8QQ8P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005184 AN005185
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Dionex Ultimate 3000 RS Thermo Dionex Ultimate 3000 RS
Column Merck SeQuant ZIC-HILIC (150 x 4.6mm,5um) Merck SeQuant ZIC-HILIC (150 x 4.6mm,5um)
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
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