ArticleAntioxidants & redox signaling2015
Antimalarial NADPH-Consuming Redox-Cyclers As Superior Glucose-6-Phosphate Dehydrogenase Deficiency Copycats.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Synthesis of Methoxylated Benzoxanthones as Drug Metabolites of Antischistosomal Schistodiones-A Limited Environmental Risk.Molecules (Basel, Switzerland) · 2026Article
- The heme A synthase Cox15, as a target of redox-active 3-benzylmenadiones with antiparasitic activity.Antimicrobial agents and chemotherapy · 2026Article
- Synthesis, Antiprotozoal Activity, and Physicochemical Evaluation of Benzamido-Menadione Derivatives.International journal of molecular sciences · 2025Article
- Design, Synthesis and Antiplasmodial Activities of a Library of Fluorine-Based 3-Benzylmenadiones.Molecules (Basel, Switzerland) · 2025Article
- Synthesis of 1,2,3-Triazole-Methyl-Menadione Derivatives: Evaluation of Electrochemical and Antiparasitic Properties against two Blood-Dwelling Parasites.ChemMedChem · 2025Article
- Pharmacomodulation of the Redox-Active Lead Plasmodione: Synthesis of Substituted 2-Benzylnaphthoquinone Derivatives, Antiplasmodial Activities, and Physicochemical Properties.International journal of molecular sciences · 2025Article
- Regioselective Synthesis of Potential Non-Quinonoid Prodrugs of Plasmodione: Antiparasitic Properties Against Two Hemoglobin-Feeding Parasites and Drug Metabolism Studies.Molecules (Basel, Switzerland) · 2024Article
- Real-time measurements of ATP dynamics via ATeams inAntimicrobial agents and chemotherapy · 2024Article
- Redox integration of signaling and metabolism in a head and neck cancer model of radiation resistance using COSMFrontiers in oncology · 2022Article
- Article
- The compound 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras-mutated liver cancer cells.Experimental and therapeutic medicine · 2020Article
- In Vivo Imaging with Genetically Encoded Redox Biosensors.International journal of molecular sciences · 2020Review
- Arylmethylamino steroids as antiparasitic agents.Nature communications · 2017Article
- Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives.Molecules (Basel, Switzerland) · 2017Article
- Pharmacomodulation of the Antimalarial Plasmodione: Synthesis of Biaryl- and N-Arylalkylamine Analogues, Antimalarial Activities and Physicochemical Properties.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
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
aimsEarly phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum were shown to protect G6PD-deficient populations from severe malaria. Here, we investigated the mechanism of a novel antimalarial series, namely 3-[substituted-benzyl]-menadiones, to understand whether these NADPH-consuming redox-cyclers, which induce oxidative stress, mimic the natural protection of G6PD deficiency.
resultsWe demonstrated that the key benzoylmenadione metabolite of the lead compound acts as an efficient redox-cycler in NADPH-dependent methaemoglobin reduction, leading to the continuous formation of reactive oxygen species, ferrylhaemoglobin, and subsequent haemichrome precipitation. Structure-activity relationships evidenced that both drug metabolites and haemoglobin catabolites contribute to potentiate drug effects and inhibit parasite development. Disruption of redox homeostasis by the lead benzylmenadione was specifically induced in Plasmodium falciparum parasitized erythrocytes and not in non-infected cells, and was visualized via changes in the glutathione redox potential of living parasite cytosols. Furthermore, the redox-cycler shows additive and synergistic effects in combination with compounds affecting the NADPH flux in vivo. INNOVATION: The lead benzylmenadione 1c is the first example of a novel redox-active agent that mimics the behavior of a falciparum parasite developing inside a G6PD-deficient red blood cell (RBC) giving rise to malaria protection, and it exerts specific additive effects that are inhibitory to parasite development, without harm for non-infected G6PD-sufficient or -deficient RBCs.
conclusionThis strategy offers an innovative perspective for the development of future antimalarial drugs for G6PD-sufficient and -deficient populations.
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