ArticleACS infectious diseases2016
Monoclonal Antibodies That Recognize the Alkylation Signature of Antimalarial Ozonides OZ277 (Arterolane) and OZ439 (Artefenomel).
Article in ACS infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
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- Recent advances, challenges and updates on the development of therapeutics for malaria.EXCLI journal · 2024Review
- Peroxide Antimalarial Drugs Target Redox Homeostasis inACS infectious diseases · 2022Article
- Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures.Journal of pharmaceutical analysis · 2021Review
- A Proteasome Mutation SensitizesACS infectious diseases · 2021Article
- Article
- System-wide biochemical analysis reveals ozonide antimalarials initially act by disrupting Plasmodium falciparum haemoglobin digestion.PLoS pathogens · 2020Article
- Structure-Activity Relationship of Antischistosomal Ozonide Carboxylic Acids.Journal of medicinal chemistry · 2020Article
- Covalent Plasmodium falciparum-selective proteasome inhibitors exhibit a low propensity for generating resistance in vitro and synergize with multiple antimalarial agents.PLoS pathogens · 2019Article
- The past, present and future of anti-malarial medicines.Malaria journal · 2019Review
- New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum.Malaria journal · 2018Article
- Increasing the Strength and Production of Artemisinin and Its Derivatives.Molecules (Basel, Switzerland) · 2018Review
- Protein Degradation Systems as Antimalarial Therapeutic Targets.Trends in parasitology · 2017Review
- In vitro activity of anti-malarial ozonides against an artemisinin-resistant isolate.Malaria journal · 2017Article
- A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2016Article
- A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.Angewandte Chemie (International ed. in English) · 2016Article
- Rearrangements of organic peroxides and related processes.Beilstein journal of organic chemistry · 2016Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery of numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides OZ277 (arterolane) and OZ439 (artefenomel). Despite the critical importance of artemisinin combination therapies (ACTs), the precise mode of action of peroxidic antimalarials is not fully understood. However, it has long been proposed that the peroxide bond in artemisinin and other antimalarial peroxides undergoes reductive activation by ferrous heme released during hemoglobin digestion to produce carbon-centered radicals that alkylate heme and parasite proteins. To probe the mode of action of OZ277 and OZ439, this paper now describes initial studies with monoclonal antibodies that recognize the alkylation signature (sum of heme and protein alkylation) of these synthetic peroxides. Immunofluorescence experiments conducted with ozonide-treated parasite cultures showed that ozonide alkylation is restricted to the parasite, as no signal was found in the erythrocyte or its membrane. In Western blot experiments with ozonide-treated
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