ArticleAntimicrobial agents and chemotherapy2016
Metabolomics-Based Screening of the Malaria Box Reveals both Novel and Established Mechanisms of Action.
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 55 papers.
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55 citing papers in PubMed, 122 citations in OpenAlex.
- Article
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- Untargeted metabolomics for triaging of cytochrome b inhibitors during Chagas' disease drug discovery.PLoS neglected tropical diseases · 2026Article
- Deconvolution of the On-Target Activity of Plasmepsin V Peptidomimetics inACS infectious diseases · 2025Article
- Novel heterospirocyclic antimalarials with activity against artemisinin- and multidrug-resistant P. falciparum malaria.International journal for parasitology. Drugs and drug resistance · 2025Article
- Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4.Journal of medicinal chemistry · 2025Article
- Integral Solvent-Induced Protein Precipitation for Target-Engagement Studies inACS infectious diseases · 2024Article
- Property and Activity Refinement of Dihydroquinazolinone-3-carboxamides as Orally Efficacious Antimalarials that Target PfATP4.Journal of medicinal chemistry · 2024Article
- Chemoproteomics validates selective targeting ofeLife · 2024Article
- Chemo-proteomics in antimalarial target identification and engagement.Medicinal research reviews · 2023Review
- Recent metabolomic developments for antimalarial drug discovery.Parasitology research · 2022Review
- Current and emerging target identification methods for novel antimalarials.International journal for parasitology. Drugs and drug resistance · 2022Review
- Therapeutic Potential of Plant Oxylipins.International journal of molecular sciences · 2022Review
- Genetic and chemical validation ofeLife · 2022Article
- The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.Traffic (Copenhagen, Denmark) · 2022Article
- Metabolomics-based phenotypic screens for evaluation of drug synergy via direct-infusion mass spectrometry.iScience · 2022Article
- A new mass spectral library for high-coverage and reproducible analysis of the Plasmodium falciparum-infected red blood cell proteome.GigaScience · 2022Article
- Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention.Cell chemical biology · 2022Article
- Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Article
- Targeting malaria parasites with novel derivatives of azithromycin.Frontiers in cellular and infection microbiology · 2022Article
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9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
High-throughput phenotypic screening of chemical libraries has resulted in the identification of thousands of compounds with potent antimalarial activity, although in most cases, the mechanism(s) of action of these compounds remains unknown. Here we have investigated the mode of action of 90 antimalarial compounds derived from the Malaria Box collection using high-coverage, untargeted metabolomics analysis. Approximately half of the tested compounds induced significant metabolic perturbations in in vitro cultures of Plasmodium falciparum In most cases, the metabolic profiles were highly correlated with known antimalarials, in particular artemisinin, the 4-aminoquinolines, or atovaquone. Select Malaria Box compounds also induced changes in intermediates in essential metabolic pathways, such as isoprenoid biosynthesis (i.e., 2-C-methyl-d-erythritol 2,4-cyclodiphosphate) and linolenic acid metabolism (i.e., traumatic acid). This study provides a comprehensive database of the metabolic perturbations induced by chemically diverse inhibitors and highlights the utility of metabolomics for triaging new lead compounds and defining specific modes of action, which will assist with the development and optimization of new antimalarial drugs.
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