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.
| Study ID | ST003160 |
| Study Title | New class of heterospirocyclic compounds present strong and rapid activity against artemisinin- and multidrug-resistant P. falciparum parasites |
| Study Summary | Malaria 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 Name | Giannangelo |
| First Name | Carlo |
| Address | 381 Royal Parade, Parkville, Victoria, 3052, Australia |
| carlo.giannangelo@monash.edu | |
| Phone | 99039282 |
| Submit Date | 2024-04-06 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-04-29 |
| Release Version | 1 |
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Project:
| Project ID: | PR001965 |
| Project DOI: | doi: 10.21228/M8QQ8P |
| Project Title: | New class of heterospirocyclic compounds present strong and rapid activity against artemisinin- and multidrug-resistant P. falciparum parasites |
| Project Summary: | Malaria 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 Name: | Giannangelo |
| First Name: | Carlo |
| Address: | 381 Royal Parade, Parkville, Victoria, 3052, Australia |
| Email: | carlo.giannangelo@monash.edu |
| Phone: | 99039282 |
