ArticleACS medicinal chemistry letters2014
Evaluation of aminohydantoins as a novel class of antimalarial agents.
Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Plasmepsins as Antimalarial Drug Targets-Then, Now, and the Future.Medicinal research reviews · 2026Review
- Identification of a Novel 1,3,4-Thiadiazole-Based Scaffold as a Plasmepsin V Inhibitor.ACS omega · 2026Article
- Article
- Babesia divergens host cell egress is mediated by essential and druggable kinases and proteases.Nature microbiology · 2026Article
- Synthesis of β-fluoropyrrolidines designed to reduce hERG affinity in a class of antiparasitic compounds.ChemistrySelect · 2025Article
- Unravelling the mode of action of the Tres Cantos Antimalarial Set (TCAMS): investigating the mechanism of potent antimalarial compounds potentially targeting the human serotonin receptor.Malaria journal · 2025Article
- Macrocyclic Peptidomimetic Plasmepsin X Inhibitors with PotentJournal of medicinal chemistry · 2023Article
- Activation of themBio · 2023Article
- Discovery and Characterization of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors and Preclinical Safety Assessment ofJournal of medicinal chemistry · 2022Article
- Maturation and substrate processing topography of the Plasmodium falciparum invasion/egress protease plasmepsin X.Nature communications · 2022Article
- Targeting malaria parasite invasion of red blood cells as an antimalarial strategy.FEMS microbiology reviews · 2019Review
- 4-Aryl Pyrrolidines as a Novel Class of Orally Efficacious Antimalarial Agents. Part 1: Evaluation of 4-Aryl- N-benzylpyrrolidine-3-carboxamides.Journal of medicinal chemistry · 2019Article
- Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion.Science (New York, N.Y.) · 2017Article
- Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control.Journal of the American Chemical Society · 2017Article
- Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum.Molecules (Basel, Switzerland) · 2016Article
- Evaluation of spiropiperidine hydantoins as a novel class of antimalarial agents.Bioorganic & medicinal chemistry · 2015Article
- Malaria medicines: a glass half full?Nature reviews. Drug discovery · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 4 institutions in 2 countries.
Funding
Abstract
Given the threat of drug resistance, there is an acute need for new classes of antimalarial agents that act via a unique mechanism of action relative to currently used drugs. We have identified a set of druglike compounds within the Tres Cantos Anti-Malarial Set (TCAMS) which likely act via inhibition of a Plasmodium aspartic protease. Structure-activity relationship analysis and optimization of these aminohydantoins demonstrate that these compounds are potent nanomolar inhibitors of the Plasmodium aspartic proteases PM-II and PM-IV and likely one or more other Plasmodium aspartic proteases. Incorporation of a bulky group, such as a cyclohexyl group, on the aminohydantion N-3 position gives enhanced antimalarial potency while reducing inhibition of human aspartic proteases such as BACE. We have identified compound 8p (CWHM-117) as a promising lead for optimization as an antimalarial drug with a low molecular weight, modest lipophilicity, oral bioavailability, and in vivo antimalarial activity in mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.