ReviewCurrent pharmaceutical design2013
1,4-naphthoquinones and other NADPH-dependent glutathione reductase-catalyzed redox cyclers as antimalarial agents.
Review in Current pharmaceutical design, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 68 citations in OpenAlex.
- Two Novel 1,4-Naphthoquinone Derivatives as Potent Agents Against Multidrug-Resistant Staphylococcus aureus and Pathogenic Gram-Positive Bacteria.Drug development research · 2026Article
- Analysis of the interaction of antimalarial agents with Plasmodium falciparum glutathione reductase through molecular mechanical calculations.Journal of molecular modeling · 2024Article
- Participation of Oxidative Stress in the Activity of Compounds Isolated fromMolecules (Basel, Switzerland) · 2023Article
- Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.International journal of molecular sciences · 2022Review
- Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity.International journal of molecular sciences · 2021Review
- Chlorinated plastoquinone analogs that inhibit Staphylococcus epidermidis and Candida albicans growth.Folia microbiologica · 2020Article
- ATP Hydrolysis Determines Cold Tolerance by Regulating Available Energy for Glutathione Synthesis in Rice Seedling Plants.Rice (New York, N.Y.) · 2020Article
- Tafenoquine: A Step toward Malaria Elimination.Biochemistry · 2020Article
- Antiplasmodial Activity of Nitroaromatic Compounds: Correlation with Their Reduction Potential and Inhibitory Action onMolecules (Basel, Switzerland) · 2019Article
- Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.BMC genomics · 2017Article
- QSAR modeling and chemical space analysis of antimalarial compounds.Journal of computer-aided molecular design · 2017Article
- Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives.Molecules (Basel, Switzerland) · 2017Article
- Effects of a novel β-lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis.International journal for parasitology. Drugs and drug resistance · 2016Article
- 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
- Cytotoxicity, hemolysis andToxicology reports · 2016Article
- Synthesis and evaluation of 1,4-naphthoquinone ether derivatives as SmTGR inhibitors and new anti-schistosomal drugs.The FEBS journal · 2015Article
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Myristicyclins A and B: antimalarial procyanidins from Horsfieldia spicata from Papua New Guinea.Organic letters · 2014Article
- The antimalarial activities of methylene blue and the 1,4-naphthoquinone 3-[4-(trifluoromethyl)benzyl]-menadione are not due to inhibition of the mitochondrial electron transport chain.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The homodimeric flavoenzyme glutathione reductase catalyzes NADPH-dependent glutathione disulfide reduction. This reaction is important for keeping the redox homeostasis in human cells and in the human pathogen Plasmodium falciparum. Different types of NADPH-dependent disulfide reductase inhibitors were designed in various chemical series to evaluate the impact of each inhibition mode on the propagation of the parasites. Against malaria parasites in cultures the most potent and specific effects were observed for redox-active agents acting as subversive substrates for both glutathione reductases of the Plasmodium-infected red blood cells. In their oxidized form, these redox-active compounds are reduced by NADPH-dependent flavoenzyme-catalyzed reactions in the cytosol of infected erythrocytes. In their reduced forms, these compounds can reduce molecular oxygen to reactive oxygen species, or reduce oxidants like methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Furthermore, studies on a fluorinated suicide-substrate of the human glutathione reductase indicate that the glutathione reductase-catalyzed bioactivation of 3-benzylnaphthoquinones to the corresponding reduced 3-benzoyl metabolites is essential for the observed antimalarial activity. In conclusion, the antimalarial lead naphthoquinones are suggested to perturb the major redox equilibria of the targeted cells. These effects result in developmental arrest of the parasite and contribute to the removal of the parasitized erythrocytes by macrophages.
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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.