ArticleAntimicrobial agents and chemotherapy2009
Compounds structurally related to ellagic acid show improved antiplasmodial activity.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 53 citations in OpenAlex.
- Revisiting Glutathione Transferases ofPharmaceuticals (Basel, Switzerland) · 2026Review
- In vitro antiplasmodial activity and toxicological profile of extracts, fractions and chemical constituents of leaves and stem bark from Dacryodes edulis (Burseraceae).BMC complementary medicine and therapies · 2023Article
- Ellagic Acid Induces in vitro Alkalinisation of the Digestive Vacuole in Drug-Sensitive Plasmodium falciparum Strain.The Malaysian journal of medical sciences : MJMS · 2022Article
- Intranasal Delivery of Recombinant S100A8 Protein Delays Lung Cancer Growth by Remodeling the Lung Immune Microenvironment.Frontiers in immunology · 2022Article
- Identification of 3,3'-O-dimethylellagic acid and apigenin as the main antiplasmodial constituents of Endodesmia calophylloides Benth and Hymenostegia afzelii (Oliver.) Harms.BMC complementary medicine and therapies · 2021Article
- Redox interactome in malaria parasite Plasmodium falciparum.Parasitology research · 2021Review
- 4-Chlorothymol Exerts Antiplasmodial Activity Impeding Redox Defense System inFrontiers in pharmacology · 2021Article
- Structure-Based Screening ofFrontiers in pharmacology · 2020Article
- Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: characterization of the Plasmodium vivax enzyme and inhibitor studies.Malaria journal · 2019Article
- Hydrogen peroxide dynamics in subcellular compartments of malaria parasites using genetically encoded redox probes.Scientific reports · 2017Article
- H2O2 dynamics in the malaria parasite Plasmodium falciparum.PloS one · 2017Article
- New molecular settings to support in vivo anti-malarial assays.Malaria journal · 2016Article
- TrxR1 as a potent regulator of the Nrf2-Keap1 response system.Antioxidants & redox signaling · 2015Review
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Liver-Stage Specific Response among Endemic Populations: Diet and Immunity.Frontiers in immunology · 2015Review
- Assessment of the in vitro antiprotozoal and cytotoxic potential of 20 selected medicinal plants from the island of Soqotra.Molecules (Basel, Switzerland) · 2012Article
- In vitro activity of extracts and isolated polyphenols from West African medicinal plants against Plasmodium falciparum.Parasitology research · 2012Article
- Implication of glutathione in the in vitro antiplasmodial mechanism of action of ellagic acid.PloS one · 2012Article
- The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue.Redox report : communications in free radical research · 2011Article
- Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria.Malaria journal · 2010Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cancer chemopreventive agent ellagic acid (EA) is a known inhibitor of glutathione S-transferases (GSTs) and possesses antiplasmodial activities in the upper-nanomolar range. In the recent drug development approach, the properties of the active site of Plasmodium falciparum GST were exploited for inhibitor design by introducing one or two additional hydroxyl groups into EA, yielding flavellagic acid (FEA) and coruleoellagic acid (CEA), respectively. Indeed, the inhibition of P. falciparum GST was improved with the increasing hydrophilicity of the planar polyaromatic ring system. Studying the effects of the two compounds on the central redox enzymes of Plasmodium revealed that glutathione reductase and thioredoxin reductase also are inhibited in the lower-micromolar range. Both compounds had strong antiplasmodial activity in the lower-nanomolar range and were particularly effective against chloroquine (CQ)-resistant P. falciparum strains. Neither FEA nor CEA showed cytotoxic effects on human cells. This was supported by negligible changes in transcript levels and enzyme activities of redox enzymes in human A549 cells upon treatment with the compounds. In Plasmodium, however, CEA treatment resulted in a marked downregulation of most antioxidant genes studied and impaired mainly the trophozoite stage of the parasites. In addition, EA, CEA, and FEA were found to strongly inhibit in vitro heme aggregation. In vitro and preliminary in vivo studies indicated that, compared to CQ, CEA is a slowly acting compound and is able to significantly improve the survival of Plasmodium berghei-infected mice. We conclude that FEA and CEA are promising antimalarial compounds that deserve to be studied further.
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