ArticleFree radical biology & medicine2012
New antimalarial indolone-N-oxides, generating radical species, destabilize the host cell membrane at early stages of Plasmodium falciparum growth: role of band 3 tyrosine phosphorylation.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Imatinib augments standard malaria combination therapy without added toxicity.The Journal of experimental medicine · 2021Trial
- Interplay Between Metabolic Pathways and Increased Oxidative Stress in Human Red Blood Cells.Cells · 2024Review
- Syk Kinase Inhibitors Synergize with Artemisinins by Enhancing Oxidative Stress inAntioxidants (Basel, Switzerland) · 2020Article
- Signaling Response to Transient Redox Stress in Human Isolated T Cells: Molecular Sensor Role of Syk Kinase and Functional Involvement of IL2 Receptor and L-Selectine.Sensors (Basel, Switzerland) · 2020Article
- Article
- Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives.Molecules (Basel, Switzerland) · 2017Article
- The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites.Antimicrobial agents and chemotherapy · 2016Article
- A spiral scaffold underlies cytoadherent knobs in Plasmodium falciparum-infected erythrocytes.Blood · 2016Article
- Inhibition of an Erythrocyte Tyrosine Kinase with Imatinib Prevents Plasmodium falciparum Egress and Terminates Parasitemia.PloS one · 2016Article
- Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its Phosphorylation by p (72) Syk.Oxidative medicine and cellular longevity · 2016Article
- The influence of host genetics on erythrocytes and malaria infection: is there therapeutic potential?Malaria journal · 2015Review
- Advances in Development of New Treatment for Leishmaniasis.BioMed research international · 2015Review
- Circulating membrane-derived microvesicles in redox biology.Free radical biology & medicine · 2014Review
- Oxidative stress and β-thalassemic erythroid cells behind the molecular defect.Oxidative medicine and cellular longevity · 2013Review
- 1,4-naphthoquinones and other NADPH-dependent glutathione reductase-catalyzed redox cyclers as antimalarial agents.Current pharmaceutical design · 2013Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Although indolone-N-oxide (INODs) genereting long-lived radicals possess antiplasmodial activity in the low-nanomolar range, little is known about their mechanism of action. To explore the molecular basis of INOD activity, we screened for changes in INOD-treated malaria-infected erythrocytes (Pf-RBCs) using a proteomics approach. At early parasite maturation stages, treatment with INODs at their IC(50) concentrations induced a marked tyrosine phosphorylation of the erythrocyte membrane protein band 3, whereas no effect was observed in control RBCs. After INOD treatment of Pf-RBCs we also observed: (i) accelerated formation of membrane aggregates containing hyperphosphorylated band 3, Syk kinase, and denatured hemoglobin; (ii) dose-dependent release of microvesicles containing the membrane aggregates; (iii) reduction in band 3 phosphorylation, Pf-RBC vesiculation, and antimalarial effect of INODs upon addition of Syk kinase inhibitors; and (iv) correlation between the IC(50) and the INOD concentrations required to induce band 3 phosphorylation and vesiculation. Together with previous data demonstrating that tyrosine phosphorylation of oxidized band 3 promotes its dissociation from the cytoskeleton, these results suggest that INODs cause a profound destabilization of the Pf-RBC membrane through a mechanism apparently triggered by the activation of a redox signaling pathway rather than direct oxidative damage.
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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.