ArticleNature communications2024
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Unpacking boxes: identification of novel inhibitors of malaria parasite invasion.International journal for parasitology. Drugs and drug resistance · 2026Article
- A bridge-like lipid transfer protein is critical for generation of invasive stages in malaria parasites.Nature communications · 2026Article
- Exploration and Characterization of the Antimalarial Activity of Pyrimidine-2,4-Diamines for which Resistance is Mediated by the ABCI3 Transporter.ChemMedChem · 2026Article
- Deconvolution of the On-Target Activity of Plasmepsin V Peptidomimetics inACS infectious diseases · 2025Article
- Optimization and Characterization of the Antimalarial Activity ofJournal of medicinal chemistry · 2025Article
- Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4.Journal of medicinal chemistry · 2025Article
- Quinoxaline-based anti-schistosomal compounds have potent anti-plasmodial activity.PLoS pathogens · 2025Article
- Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4.ChemMedChem · 2024Article
- Exploration and characterization of the antimalarial activity of cyclopropyl carboxamides that target the mitochondrial protein, cytochrome b.European journal of medicinal chemistry · 2024Article
- An adaptable, fit-for-purpose screening approach with high-throughput capability to determine speed of action and stage specificity of anti-malarial compounds.Antimicrobial agents and chemotherapy · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
31 authors.
Funding
Abstract
With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite's lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
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