ArticleBioorganic & medicinal chemistry2015
Evaluation of spiropiperidine hydantoins as a novel class of antimalarial agents.
Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Babesia divergens host cell egress is mediated by essential and druggable kinases and proteases.Nature microbiology · 2026Article
- Synthesis, Antitumor Activities, and Apoptosis-Inducing Activities of Schiff's Bases Incorporating Imidazolidine-2,4-dione Scaffold: Molecular Docking Studies and Enzymatic Inhibition Activities.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Synthesis of β-fluoropyrrolidines designed to reduce hERG affinity in a class of antiparasitic compounds.ChemistrySelect · 2025Article
- Spiro heterocycles bearing piperidine moiety as potential scaffold for antileishmanial activity: synthesis, biological evaluation, andJournal of enzyme inhibition and medicinal chemistry · 2023Article
- [3+2]-Cycloaddition of azomethine ylides to 5-methylidene-3-aryl-2-сhalcogen-imidazolones: access to dispiro indolinone-pyrrolidine-imidazolones.Royal Society open science · 2022Article
- Synthesis and Antiplasmodial Activity of Novel Bioinspired Imidazolidinedione Derivatives.Biomolecules · 2020Article
- Synthesis and Antimalarial Activity of 1,4-Disubstituted Piperidine Derivatives.Molecules (Basel, Switzerland) · 2020Article
- 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
- Potent antiplasmodial extracts and fractions from Terminalia mantaly and Terminalia superba.Malaria journal · 2018Article
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
Abstract
Given the rise of parasite resistance to all currently used antimalarial drugs, the identification of novel chemotypes with unique mechanisms of action is of paramount importance. Since Plasmodium expresses a number of aspartic proteases necessary for its survival, we have mined antimalarial datasets for drug-like aspartic protease inhibitors. This effort led to the identification of spiropiperidine hydantoins, bearing similarity to known inhibitors of the human aspartic protease β-secretase (BACE), as new leads for antimalarial drug discovery. Spiropiperidine hydantoins have a dynamic structure-activity relationship profile with positions identified as being tolerant of a variety of substitution patterns as well as a key piperidine N-benzyl phenol pharmacophore. Lead compounds 4e (CWHM-123) and 12k (CWHM-505) are potent antimalarials with IC50 values against Plasmodium falciparum 3D7 of 0.310 μM and 0.099 μM, respectively, and the former features equivalent potency on the chloroquine-resistant Dd2 strain. Remarkably, these compounds do not inhibit human aspartic proteases BACE, cathepsins D and E, or Plasmodium plasmepsins II and IV despite their similarity to known BACE inhibitors. Although the current leads suffer from poor metabolic stability, they do fit into a drug-like chemical property space and provide a new class of potent antimalarial agents for further study.
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