Cobbold, Simon A.; Chua, Hwa H.; Nijaga, Brunda; Creek, Darren J.; Ralph, Stuart A.; McConville, Malcolm J. published the artcile< Metabolic dysregulation induced in Plasmodium falciparum by dihydroartemisinin and other front-line antimalarial drugs>, Reference of 1223001-51-1, the main research area is Plasmodium dihydroartemisinin antimalarial metabolic dysregulation; Plasmodium; antimalarial; artemisinin; atovaquone; chloroquine; drug screening; malaria; metabolite; metabolomics; torin.
Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clin. antimalarial drugs and inhibitors on Plasmodium falciparum asexual blood stages. Drug-induced changes in metabolite levels in P. falciparum-infected erythrocytes were monitored over time using gas chromatog.-MS and liquid chromatog.-MS and changes in specific metabolic fluxes confirmed by nonstationary [13C]-glucose labeling. Dihydroartemisinin (DHA) was found to disrupt Hb catabolism within 1 h of exposure, resulting in a transient decrease in Hb-derived peptides. Unexpectedly, it also disrupted pyrimidine biosynthesis, resulting in increased [13C]-glucose flux toward malate production, potentially explaining the susceptibility of P. falciparum to DHA during early blood-stage development. Unique metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and methylene blue. We also show that this approach can be used to identify the mode of action of novel antimalarials, such as the compound Torin 2, which inhibits Hb catabolism.
Journal of Infectious Diseases published new progress about Antimalarials. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Reference of 1223001-51-1.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem