ArticleAntimicrobial agents and chemotherapy2004
Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 326 citations in OpenAlex.
- IgG3 and IL10 are effective biomarkers for monitoring therapeutic effectiveness in Post Kala-Azar Dermal Leishmaniasis.PLoS neglected tropical diseases · 2021Trial
- Integrating Molecular Similarity and AlphaFold-Based Structural Alignment for Target Discovery inPharmaceuticals (Basel, Switzerland) · 2026Article
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- In Vitro and Ultrastructural Evaluation of the Cytotoxic and Antileishmanial Activities of Thiosemicarbazone Compounds Against Promastigotes and Axenic Amastigotes ofTropical medicine and infectious disease · 2025Article
- The Potential Role of Sanguinarine as an Inhibitor of Leishmania PP2C in the Induction of Apoptosis.Acta parasitologica · 2025Article
- The carbonic anhydrase enzymes as new targets for the management of neglected tropical diseases.Archiv der Pharmazie · 2025Review
- An inclusive assessment of apoptosis mechanisms inCurrent research in parasitology & vector-borne diseases · 2025Review
- Synthesis of a dehydrodieugenol B derivative as a lead compound for visceral leishmaniasis-mechanism of action andAntimicrobial agents and chemotherapy · 2024Article
- Milteforan, a promising veterinary commercial product against feline sporotrichosis.Microbiology spectrum · 2024Article
- Synergistic Effects of Artesunate in Combination with Amphotericin B and Miltefosine againstAntibiotics (Basel, Switzerland) · 2024Article
- Robust leishmanicidal upshot of some new diphenyl triazine-based molecules.RSC advances · 2024Article
- Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular CaBiomolecules · 2024Review
- Milteforan, a promising veterinary commercial product against feline sporotrichosis.bioRxiv : the preprint server for biology · 2024Article
- In Vitro and Ex Vivo Synergistic Effect of Pyrvinium Pamoate Combined with Miltefosine and Paromomycin againstTropical medicine and infectious disease · 2024Article
- Polymeric nanoparticles containing kojic acid induce structural alterations and apoptosis-like death inFrontiers in pharmacology · 2024Article
- Article
- Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas Disease.Pathogens (Basel, Switzerland) · 2023Review
- A short-term method to evaluate anti-leishmania drugs by inhibition of stage differentiation in Leishmania mexicana using flow cytometry.Experimental parasitology · 2023Article
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Quantum Biochemistry Screening and In Vitro Evaluation ofInternational journal of molecular sciences · 2022Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Miltefosine (hexadecylphosphocholine [HePC]) has proved to be a potent oral treatment for human visceral leishmaniasis due to Leishmania donovani. The molecular mechanisms that contribute to the antileishmanial activity of HePC are still unknown. We report that in wild-type promastigotes of Leishmania donovani HePC is able to induce a cell death process with numerous cytoplasmic, nuclear, and membrane features of metazoan apoptosis, including cell shrinkage, DNA fragmentation into oligonucleosome-sized fragments, and phosphatidylserine exposure. None of these changes were detected in an HePC-resistant clone treated with the same drug concentration. Therefore, HePC does not appear to kill L. donovani promastigotes by a direct toxic mechanism but, rather, kills the promastigotes by an indirect one. Pretreatment of wild-type promastigotes with two broad caspase inhibitors, z-Val-Ala-DL-Asp(methoxy)-fluoromethylketone and Boc-Asp(methoxy)-fluoromethylketone, as well as a broad protease inhibitor, calpain inhibitor I, prior to drug exposure interfered with DNA fragmentation but did not prevent cell shrinkage or phosphatidylserine externalization. These data suggest that at least part of the apoptotic machinery operating in wild-type promastigotes involves proteases. Identification of the death-signaling pathways activated in HePC-sensitive parasites appears to be essential for a better understanding of the molecular mechanisms of action and resistance in these parasites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.