ArticleThe Journal of antimicrobial chemotherapy2014
Rapid kill of malaria parasites by artemisinin and semi-synthetic endoperoxides involves ROS-dependent depolarization of the membrane potential.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 145 citations in OpenAlex.
- Allicin-based biomimetic nanoparticles of the erythrocyte membrane for the delivery of lumefantrine to enhance its antimalarial effect.International journal of pharmaceutics: X · 2026Article
- Why are iron chelators not as effective as artemisinin in killing malaria parasites?Parasites & vectors · 2026Article
- Polypharmacology in malaria treatment: single drugs, multiple mechanisms, greater impact.Trends in parasitology · 2026Review
- Evaluating Toxicity and Anti-Osteogenic Activity of Artemisinin-Inspired Endoperoxides in Zebrafish Larvae.Toxics · 2026Article
- Fluorescence-based bioassay for the detection of changes in mitochondrial physiology during artemisinin-induced growth arrest of blood-stage Plasmodium falciparum.Scientific reports · 2025Article
- Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025Review
- Plant-derived products as anti-leishmanials which target mitochondria: a review.Expert reviews in molecular medicine · 2025Review
- Comparison of the composition and antiplasmodial activity of Artemisia annua teas using an untargeted metabolomic approach.PloS one · 2025Article
- Oxidative stress in malaria and typhoid fever: A scoping review of the pathogenic mechanisms and therapeutic implications.PLOS global public health · 2025Article
- The Antiviral and Antimalarial Prodrug Artemisinin from theCurrent issues in molecular biology · 2024Review
- Fabrication of Phytosome with Enhanced Activity ofInternational journal of nanomedicine · 2024Article
- Indigenous medicinal plants used in folk medicine for malaria treatment in Kwara State, Nigeria: an ethnobotanical study.BMC complementary medicine and therapies · 2023Article
- Micromolar Dihydroartemisinin Concentrations Elicit Lipoperoxidation inAntioxidants (Basel, Switzerland) · 2023Article
- Anti-Mitochondrial and Insecticidal Effects of Artemisinin againstInternational journal of molecular sciences · 2023Article
- A whole-genome scan for Artemisinin cytotoxicity reveals a novel therapy for human brain tumors.EMBO molecular medicine · 2023Article
- Transcriptome analysis ofHeliyon · 2023Article
- Erythrocyte membrane with CLIPPKF as biomimetic nanodecoy traps merozoites and attaches to infected red blood cells to prevent Plasmodium infection.Journal of nanobiotechnology · 2023Article
- Article
- Drug Development Strategies for Malaria: With the Hope for New Antimalarial Drug Discovery-An Update.Advances in medicine · 2023Review
- Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action.Malaria journal · 2022Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesArtemisinin and artemisinin semi-synthetic derivatives (collectively known as endoperoxides) are first-line antimalarials for the treatment of uncomplicated and severe malaria. Endoperoxides display very fast killing rates and are generally recalcitrant to parasite resistance development. These key pharmacodynamic features are a result of a complex mechanism of action, the details of which lack consensus. Here, we report on the primary physiological events leading to parasite death.
methodsParasite mitochondrial (ΔΨm) and plasma membrane (ΔΨp) electrochemical potentials were measured using real-time single-cell imaging following exposure to pharmacologically relevant concentrations of endoperoxides (artemisinin, dihydroartemisinin, artesunate and the synthetic tetraoxane RKA182). In addition, mitochondrial electron transport chain components NADH:quinone oxidoreductase (alternative complex I), bc1 (complex III) and cytochrome oxidase (complex IV) were investigated to determine their functional sensitivity to the various endoperoxides.
resultsParasite exposure to endoperoxides resulted in rapid depolarization of parasite ΔΨm and ΔΨp. The rate of depolarization was decreased in the presence of a reactive oxygen species (ROS) scavenger and Fe(3+) chelators. Depolarization of ΔΨm by endoperoxides is not believed to be through the inhibition of mitochondrial electron transport chain components, owing to the lack of significant inhibition when assayed directly.
conclusionsThe depolarization of ΔΨm and ΔΨp is shown to be mediated via the generation of ROS that are initiated by iron bioactivation of endoperoxides and/or catalysed by iron-dependent oxidative stress. These data are discussed in the context of current hypotheses concerning the mode of action of endoperoxides.
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