ArticleAntimicrobial agents and chemotherapy2016
Metabolomic Profiling of the Malaria Box Reveals Antimalarial Target Pathways.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed.
- Article
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- Single-cell analysis ofbioRxiv : the preprint server for biology · 2026Article
- Effect of Stereochemistry on the Antiplasmodial Activity and Metabolomic Profile of Novel Tadalafil Analogues.ACS medicinal chemistry letters · 2026Article
- Double Mutations inbioRxiv : the preprint server for biology · 2026Article
- Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.Nature communications · 2026Article
- A Novel Class of Orally Bioavailable Phenylglycine-Benzoxaborole Conjugates with Antimalarial Activity and Potentially Novel Mechanism of Action.ACS medicinal chemistry letters · 2026Article
- Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.Malaria journal · 2026Article
- Untargeted metabolomics for triaging of cytochrome b inhibitors during Chagas' disease drug discovery.PLoS neglected tropical diseases · 2026Article
- Exploration and Characterization of the Antimalarial Activity of Pyrimidine-2,4-Diamines for which Resistance is Mediated by the ABCI3 Transporter.ChemMedChem · 2026Article
- A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite.Nature communications · 2025Article
- Deconvolution of the On-Target Activity of Plasmepsin V Peptidomimetics inACS infectious diseases · 2025Article
- Microwave-Assisted Organic Synthesis: An Eco-Friendly Method of Green Chemistry.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Epigenetically conferred ring-stage survival in Plasmodium falciparum against artemisinin treatment.Nature communications · 2025Article
- Application of Multiplatform Mass Spectrometry to the Study ofInternational journal of molecular sciences · 2025Article
- Emerging Molecular Mechanisms in Malaria Pathogenesis and Novel Therapeutic Approaches: A Focus onBiomolecules · 2025Review
- The ATM Kinase Inhibitor AZD0156 Is a Potent Inhibitor of Plasmodium Phosphatidylinositol 4-Kinase (PI4Kβ) and Is an Attractive Candidate for Medicinal Chemistry Optimization Against Malaria.Angewandte Chemie (International ed. in English) · 2025Article
- The plasmepsin-piperaquine paradox persists in Plasmodium falciparum.PLoS pathogens · 2025Article
- Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4.Journal of medicinal chemistry · 2025Article
- Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.ACS infectious diseases · 2025Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
The threat of widespread drug resistance to frontline antimalarials has renewed the urgency for identifying inexpensive chemotherapeutic compounds that are effective against Plasmodium falciparum, the parasite species responsible for the greatest number of malaria-related deaths worldwide. To aid in the fight against malaria, a recent extensive screening campaign has generated thousands of lead compounds with low micromolar activity against blood stage parasites. A subset of these leads has been compiled by the Medicines for Malaria Venture (MMV) into a collection of structurally diverse compounds known as the MMV Malaria Box. Currently, little is known regarding the activity of these Malaria Box compounds on parasite metabolism during intraerythrocytic development, and a majority of the targets for these drugs have yet to be defined. Here we interrogated the in vitro metabolic effects of 189 drugs (including 169 of the drug-like compounds from the Malaria Box) using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). The resulting metabolic fingerprints provide information on the parasite biochemical pathways affected by pharmacologic intervention and offer a critical blueprint for selecting and advancing lead compounds as next-generation antimalarial drugs. Our results reveal several major classes of metabolic disruption, which allow us to predict the mode of action (MoA) for many of the Malaria Box compounds. We anticipate that future combination therapies will be greatly informed by these results, allowing for the selection of appropriate drug combinations that simultaneously target multiple metabolic pathways, with the aim of eliminating malaria and forestalling the expansion of drug-resistant parasites in the field.
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