ArticleThe Biochemical journal1999
Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials.
Article in The Biochemical journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
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Who cites it
83 citing papers in PubMed, 257 citations in OpenAlex.
- IgG antibody response against Plasmodium falciparum aminopeptidase 1 antigen in Gabonese children living in Makokou and Franceville.Clinical and experimental immunology · 2020Trial
- Searching for new candidates for antimalarial therapy: physicochemical and in vitro evaluation of gold(I) and silver(I) N-heterocyclic carbene complexes.Malaria journal · 2026Article
- Fifty shades of iron: Unorthodox mechanisms of iron acquisition and utilization in blood-stage Plasmodium parasites.PLoS pathogens · 2026Review
- 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
- Tafenoquine Disrupts Intraerythrocytic Stages of Malaria Parasites by Inhibiting Nonclassical Pathways of β-Hematin Nucleation and Growth.Biochemistry · 2025Article
- Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chemoproteomics validates selective targeting ofeLife · 2024Article
- Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites.bioRxiv : the preprint server for biology · 2024Article
- Alkaloidal Extracts fromAdvances in pharmacological and pharmaceutical sciences · 2024Article
- Genetic basis and spatial distribution of glucose-6-phosphate dehydrogenase deficiency in ecuadorian ethnic groups: a malaria perspective.Malaria journal · 2023Article
- A non-canonical sensing pathway mediates Plasmodium adaptation to amino acid deficiency.Communications biology · 2023Article
- Molecular dynamics of G6PD variants from sub-Saharan Africa.Biochemistry and biophysics reports · 2022Article
- G6PD distribution in sub-Saharan Africa and potential risks of using chloroquine/hydroxychloroquine based treatments for COVID-19.The pharmacogenomics journal · 2021Article
- Reactive Oxygen Species as the Brainbox in Malaria Treatment.Antioxidants (Basel, Switzerland) · 2021Review
- Loss of Dihydroxyacid Dehydratase Induces Auxotrophy in Bacillus anthracis.Journal of bacteriology · 2021Article
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Chloroquine and Sulfadoxine-Pyrimethamine Resistance in Sub-Saharan Africa-A Review.Frontiers in genetics · 2021Review
- Janus sword actions of chloroquine and hydroxychloroquine against COVID-19.Cellular signalling · 2020Article
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23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The malaria parasite feeds by degrading haemoglobin in an acidic food vacuole, producing free haem moieties as a by-product. The haem in oxyhaemoglobin is oxidized from the Fe(II) state to the Fe(III) state with the consequent production of an equimolar concentration of H2O2. We have analysed the fate of haem molecules in Plasmodium falciparum-infected erythrocytes and have found that only about one third of the haem is polymerized to form haemozoin. The remainder appears to be degraded by a non-enzymic process which leads to an accumulation of iron in the parasite. A possible route for degradation of the haem is by reacting with H2O2, and we show that, under conditions designed to resemble those found in the food vacuole, i.e., at pH5.2 in the presence of protein, free haem undergoes rapid peroxidative decomposition. Chloroquine and quinacrine are shown to be efficient inhibitors of the peroxidative destruction of haem, while epiquinine, a quinoline compound with very low antimalarial activity, has little inhibitory effect. We also show that chloroquine enhances the association of haem with membranes, while epiquinine inhibits this association, and that treatment of parasitized erythrocytes with chloroquine leads to a build-up of membrane-associated haem in the parasite. We suggest that chloroquine exerts its antimalarial activity by causing a build-up of toxic membrane-associated haem molecules that eventually destroy the integrity of the malaria parasite. We have further shown that resistance-modulating compounds, such as chlorpromazine, interact with haem and efficiently inhibit its degradation. This may explain the weak antimalarial activities of these compounds.
Indexed as
Identifiers
10191268PMC1220166W2022857214What OpenQuestion holds
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.