ArticleAntimicrobial agents and chemotherapy2007
Miltefosine (hexadecylphosphocholine) inhibits cytochrome c oxidase in Leishmania donovani promastigotes.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 125 citations in OpenAlex.
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- Targeting mitochondrial bioenergetics: the "Achilles' heel" of Leishmania.Parasites & vectors · 2026Article
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Targeting Trypanothione Synthetase and Trypanothione Reductase: Development of Common Inhibitors to Tackle Trypanosomatid Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Repositioning of moxidectin: a promising approach in cutaneous leishmaniasis therapy.Parasite (Paris, France) · 2025Article
- Miltefosine impacts small molecule transport in Gram-positive bacteria.RSC chemical biology · 2024Article
- Synergistic Effects of Artesunate in Combination with Amphotericin B and Miltefosine againstAntibiotics (Basel, Switzerland) · 2024Article
- Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular CaBiomolecules · 2024Review
- In Vitro and Ex Vivo Synergistic Effect of Pyrvinium Pamoate Combined with Miltefosine and Paromomycin againstTropical medicine and infectious disease · 2024Article
- Epoxy-a-lapachone in nanosystem: a prototype drug for leishmaniasis assessed in the binomial BALB/c - Leishmania (Leishmania) amazonensis.Memorias do Instituto Oswaldo Cruz · 2024Article
- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
- The Antileishmanial Activity of Eugenol Associated with Lipid Storage Reduction Rather Than Membrane Properties Alterations.Molecules (Basel, Switzerland) · 2023Article
- A new immunochemotherapy schedule for visceral leishmaniasis in a hamster model.Parasitology research · 2022Article
- Transcriptome Analysis of Intracellular Amastigotes of ClinicalMicroorganisms · 2022Article
- Unraveling of interacting protein network of chaperonin TCP1 gamma subunit of Leishmania donovani.Cell stress & chaperones · 2022Article
- In-Depth Quantitative Proteomics Characterization of In Vitro Selected Miltefosine Resistance inProteomes · 2022Article
- Different Drugs, Same End: Ultrastructural Hallmarks of Autophagy in Pathogenic Protozoa.Frontiers in microbiology · 2022Review
- Lipid and fatty acid metabolism in trypanosomatids.Microbial cell (Graz, Austria) · 2021Review
- The Search for Putative Hits in Combating Leishmaniasis: The Contributions of Natural Products Over the Last Decade.Natural products and bioprospecting · 2021Review
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Miltefosine (hexadecylphosphocholine [HePC]) is currently on trial as a first-choice, orally active drug for the treatment of visceral leishmaniasis when resistance to organic pentavalent antimonials becomes epidemic. However, data on the targets involved in its leishmanicidal mechanism have, until now, been only fragmentary. We have carried out a systematic study of the alterations induced on the bioenergetic metabolism of Leishmania donovani promastigotes by HePC. Overnight incubation with HePC caused a significant decline in the intracellular ATP levels of the parasites, together with a reduction in the oxygen consumption rate and mitochondrial depolarization, while the integrity of the plasma membrane remained undamaged. In a further step, the effects of HePC on the respiratory chain were addressed in digitonized parasites. The inhibition of the oxygen consumption rate caused by HePC was not reverted either with the uncoupling agent carbonyl cyanide p-trifluoromethoxyphenylhydrazone or with tetramethyl-p-phenylenediamine plus ascorbate, which feeds the electron transport chain at the level of cytochrome c. These results suggest that cytochrome c oxidase is a likely target in the complex leishmanicidal mechanism of HePC. This was further confirmed from the finding that this enzyme was specifically inhibited in a dose-dependent manner by HePC, but not the cytochrome c reductase, ruling out an unspecific effect of HePC on the respiratory chain.
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