ArticleAntimicrobial agents and chemotherapy2015
Antimalarial action of artesunate involves DNA damage mediated by reactive oxygen species.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Identification of Co-Existing Mutations and Gene Expression Trends Associated With K13-Mediated Artemisinin Resistance inFrontiers in genetics · 2022Pooled it
- Pharmacokinetics andAntimicrobial agents and chemotherapy · 2020Trial
- Host Reticulocyte Redox Attenuation Creates a Protective Niche for Artemisinin Tolerance in Plasmodium falciparum.The Journal of infectious diseases · 2026Article
- Cell cycle checkpoint activity in the malaria parasitemSphere · 2026Article
- Enhanced Antibacterial Activity ofJournal of functional biomaterials · 2026Article
- Glutathione redox system as a therapeutic target for Plasmodium: Opportunities, Challenges, and future perspectives.Folia microbiologica · 2026Review
- Polypharmacology in malaria treatment: single drugs, multiple mechanisms, greater impact.Trends in parasitology · 2026Review
- Article
- Antimalarial Potency ofJournal of tropical medicine · 2026Article
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
- Plasmodium falciparum DNA repair dynamics reveal unique roles for TLS polymerases and PfRad51 in genome diversification.Nucleic acids research · 2025Article
- Chrysosplenetin acts as a homeostasis stabilizer with dual-function in shattering Plasmodium berghei K173 resistance to artemisinin driven by both ABC transporters and heme-ROS/GSH axis.Parasites & vectors · 2025Article
- Computational Analysis of Plasmodium falciparum DNA Damage Inducible Protein 1 (PfDdi1): Insights into Binding of Artemisinin and its Derivatives and Implications for Antimalarial Drug Design.Cell biochemistry and biophysics · 2025Article
- Current Advances in Anticancer Properties of Heptamethine Carbocyanine DZ-1 Conjugated to Artesunate: Generation of Reactive Oxygen Species.Journal of cellular biochemistry · 2025Article
- Formononetin exerts synergistic action with artesunate against multi-drug-resistant P. falciparum arresting ring-to-schizont transition by inducing reactive oxygen species.Archives of microbiology · 2025Article
- Enhanced Antimalarial Efficacy ofAdvances in pharmacological and pharmaceutical sciences · 2025Article
- Article
- Elucidation of the Active Agents in a West African Ground Herbal Medicine Formulation That Elicit Antimalarial Activities in In Vitro and In Vivo Models.Molecules (Basel, Switzerland) · 2024Article
- Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives.Tropical medicine and infectious disease · 2024Review
- Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Artemisinin-based combination therapy (ACT) is the recommended first-line treatment for Plasmodium falciparum malaria. It has been suggested that the cytotoxic effect of artemisinin is mediated by free radicals followed by the alkylation of P. falciparum proteins. The endoperoxide bridge, the active moiety of artemisinin derivatives, is cleaved in the presence of ferrous iron, generating reactive oxygen species (ROS) and other free radicals. However, the emergence of resistance to artemisinin in P. falciparum underscores the need for new insights into the molecular mechanisms of antimalarial activity of artemisinin. Here we show that artesunate (ART) induces DNA double-strand breaks in P. falciparum in a physiologically relevant dose- and time-dependent manner. DNA damage induced by ART was accompanied by an increase in the intracellular ROS level in the parasites. Mannitol, a ROS scavenger, reversed the cytotoxic effect of ART and reduced DNA damage, and modulation of glutathione (GSH) levels was found to impact ROS and DNA damage induced by ART. Accumulation of ROS, increased DNA damage, and the resulting antiparasite effect suggest a causal relationship between ROS, DNA damage, and parasite death. Finally, we also show that ART-induced ROS production involves a potential role for NADPH oxidase, an enzyme involved in the production of superoxide anions. Our results with P. falciparum provide novel insights into previously unknown molecular mechanisms underlying the antimalarial activity of artemisinin derivatives and may help in the design of next-generation antimalarial drugs against the most virulent Plasmodium species.
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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.