ArticleAngewandte Chemie (International ed. in English)2016
A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.
Article in Angewandte Chemie (International ed. in English), 2016. 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 38 papers, 1 of them a synthesis that pooled it.
What it found
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Identification of Co-Existing Mutations and Gene Expression Trends Associated With K13-Mediated Artemisinin Resistance inFrontiers in genetics · 2022Pooled it
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- Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance.Science advances · 2025Article
- Pharmacokinetics and metabolism of artemisinin (ART) in Plasmodium yoelii: ART-heme adduct as a potential biomarker for its resistance.International journal for parasitology. Drugs and drug resistance · 2025Article
- Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract.Journal of pharmaceutical analysis · 2025Article
- Enhanced cell stress response and protein degradation capacity underlie artemisinin resistance inmSphere · 2024Article
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- Autofluorescent antimalarials by hybridization of artemisinin and coumarin:Chemical science · 2023Article
- Chemo-proteomics in antimalarial target identification and engagement.Medicinal research reviews · 2023Review
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- Peroxide Antimalarial Drugs Target Redox Homeostasis inACS infectious diseases · 2022Article
- The Role of the Iron Protoporphyrins Heme and Hematin in the Antimalarial Activity of Endoperoxide Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Antimalarial Natural Products.Progress in the chemistry of organic natural products · 2022Article
- Expanded scope of Griesbaum co-ozonolysis for the preparation of structurally diverse sensors of ferrous iron.RSC advances · 2021Article
- A Proteasome Mutation SensitizesACS infectious diseases · 2021Article
- Artemisinin-Based Drugs Target the Plasmodium falciparum Heme Detoxification Pathway.Antimicrobial agents and chemotherapy · 2021Article
- A click-based modular approach to introduction of peroxides onto molecules and nanostructures.RSC advances · 2020Article
- Reactivity-Based Probe of the Iron(II)-Dependent Interactome Identifies New Cellular Modulators of Ferroptosis.Journal of the American Chemical Society · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities.
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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.