| Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis. | |
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MedLine Citation:
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PMID: 20837758 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tafenoquine (TFQ), an 8-aminoquinoline analogue of primaquine, which is currently under clinical trial (phase IIb/III) for the treatment and prevention of malaria, may represent an alternative treatment for leishmaniasis. In this work, we have studied the mechanism of action of TFQ against Leishmania parasites. TFQ impaired the overall bioenergetic metabolism of Leishmania promastigotes, causing a rapid drop in intracellular ATP levels without affecting plasma membrane permeability. TFQ induced mitochondrial dysfunction through the inhibition of cytochrome c reductase (respiratory complex III) with a decrease in the oxygen consumption rate and depolarization of mitochondrial membrane potential. This was accompanied by ROS production, elevation of intracellular Ca(2+) levels and concomitant nuclear DNA fragmentation. We conclude that TFQ targets Leishmania mitochondria, leading to an apoptosis-like death process. |
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Authors:
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Luis Carvalho; Juan Román Luque-Ortega; José Ignacio Manzano; Santiago Castanys; Luis Rivas; Francisco Gamarro |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-13 |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 54 ISSN: 1098-6596 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-15 Completed Date: 2011-03-11 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 5344-51 Citation Subset: IM |
Affiliation:
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Instituto de Parasitología y Biomedicina "López-Neyra," CSIC, Granada, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Aminoquinolines / pharmacology* Antimalarials / pharmacology* Apoptosis / drug effects* Calcium / metabolism Cell Membrane / drug effects DNA Fragmentation / drug effects Electron Transport Complex III / drug effects* Leishmania / drug effects*, metabolism* Oxygen Consumption / drug effects Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Aminoquinolines; 0/Antimalarials; 0/Reactive Oxygen Species; 106635-80-7/tafenoquine; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; EC 1.10.2.2/Electron Transport Complex III |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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