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Journal article
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, v 57(5), pp 2114-2120
01 May 2013
PMID: 23439633
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- 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
- Creators
- Katharina Ehrhardt - Heidelberg UniversityElisabeth Davioud-Charvet - University of StrasbourgHangjun Ke - Drexel UniversityAkhil B. Vaidya - Drexel UniversityMichael Lanzer - Heidelberg UniversityMarcel Deponte - Heidelberg University
- Publication Details
- Antimicrobial agents and chemotherapy, v 57(5), pp 2114-2120
- Publisher
- Amer Soc Microbiology
- Number of pages
- 7
- Grant note
- UMR 7509 / Centre National de la Recherche Scientifique (CNRS, France); Centre National de la Recherche Scientifique (CNRS) AI028398 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA International Center for Frontier Research in Chemistry. Strasbourg University of Strasbourg LabEx ParaFrap ANR-11-LABX-0024 / Laboratoire d'Excellence (LabEx) ParaFrap ANRemergence program; French National Research Agency (ANR) CNRS; Centre National de la Recherche Scientifique (CNRS); European Commission R01AI028398 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000317467600015
- Scopus ID
- 2-s2.0-84876209672
- Other Identifier
- 991019168040604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy