ArticleAntimicrobial agents and chemotherapy2013
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.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- Ruthenium Complexes of Atovaquone Acting on Multiple Stages of theJournal of medicinal chemistry · 2026Article
- Synthesis of 1,2,3-Triazole-Methyl-Menadione Derivatives: Evaluation of Electrochemical and Antiparasitic Properties against two Blood-Dwelling Parasites.ChemMedChem · 2025Article
- Metal(triphenylphosphine)-atovaquone Complexes: Synthesis, Antimalarial Activity, and Suppression of Heme Detoxification.Inorganic chemistry · 2024Article
- Analysis of the interaction of antimalarial agents with Plasmodium falciparum glutathione reductase through molecular mechanical calculations.Journal of molecular modeling · 2024Article
- Methylene Blue-Based Combination Therapy with Amodiaquine Prevents Severe Malaria in an Experimental Rodent Model.Pharmaceutics · 2022Article
- Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in AfricanPharmaceuticals (Basel, Switzerland) · 2021Article
- In Vivo Imaging with Genetically Encoded Redox Biosensors.International journal of molecular sciences · 2020Review
- AntimalarialACS medicinal chemistry letters · 2020Article
- In vitro antiplasmodial activity, pharmacokinetic profiles and interference in isoprenoid pathway of 2-aniline-3-hydroxy-1.4-naphthoquinone derivatives.Malaria journal · 2018Article
- Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production.Intensive care medicine experimental · 2018Article
- Study of Methylene Blue Ototoxicity in the Guinea Pig.Journal of clinical medicine research · 2017Article
- Methylene blue and its analogues as antidepressant compounds.Metabolic brain disease · 2017Review
- Pharmacomodulation of the Antimalarial Plasmodione: Synthesis of Biaryl- and N-Arylalkylamine Analogues, Antimalarial Activities and Physicochemical Properties.Molecules (Basel, Switzerland) · 2017Article
- Design, Synthesis and Evaluation of Bifunctional Acridinine-Naphthalenediimide Redox-Active Conjugates as Antimalarials.ACS omega · 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
- Preliminary LC-MS Based Screening for Inhibitors of Plasmodium falciparum Thioredoxin Reductase (PfTrxR) among a Set of Antimalarials from the Malaria Box.Molecules (Basel, Switzerland) · 2016Article
- Cytotoxicity, hemolysis andToxicology reports · 2016Article
- Antimalarial NADPH-Consuming Redox-Cyclers As Superior Glucose-6-Phosphate Dehydrogenase Deficiency Copycats.Antioxidants & redox signaling · 2015Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Methylene blue and a series of recently developed 1,4-naphthoquinones, including 3-[4-(substituted)benzyl]-menadiones, are potent antimalarial agents in vitro and in vivo. The activity of these structurally diverse compounds against the human malaria parasite Plasmodium falciparum might involve their peculiar redox properties. According to the current theory, redox-active methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione are "subversive substrates." These agents are thought to shuttle electrons from reduced flavoproteins to acceptors such as hemoglobin-associated or free Fe(III)-protoporphyrin IX. The reduction of Fe(III)-protoporphyrin IX could subsequently prevent essential hemoglobin digestion and heme detoxification in the parasite. Alternatively, owing to their structures and redox properties, methylene blue and 1,4-naphthoquinones might also affect the mitochondrial electron transport chain. Here, we tested the latter hypothesis using an established system of transgenic P. falciparum cell lines and the antimalarial agents atovaquone and chloroquine as controls. In contrast to atovaquone, methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione do not inhibit the mitochondrial electron transport chain. A systematic comparison of the morphologies of drug-treated parasites furthermore suggests that the three drugs do not share a mechanism of action. Our findings support the idea that methylene blue and 3-[4-(trifluoromethyl)benzyl]-menadione exert their antimalarial activity as redox-active subversive substrates.
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