ArticleAntimicrobial agents and chemotherapy2014
Dronedarone, an amiodarone analog with improved anti-Leishmania mexicana efficacy.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Mannich Bases: Promising Scaffolds for the Treatment of Infectious Diseases.Current medicinal chemistry · 2025Review
- Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B.ACS omega · 2024Article
- Article
- Synthesis, Antimalarial, Antileishmanial, and Cytotoxicity Activities and Preliminary In Silico ADMET Studies of 2-(7-Chloroquinolin-4-ylamino)ethyl Benzoate Derivatives.Pharmaceuticals (Basel, Switzerland) · 2023Article
- New Insights on Heme Uptake inInternational journal of molecular sciences · 2022Article
- Effects of amiodarone, amioder, and dronedarone on Trichomonas vaginalis.Parasitology research · 2022Article
- Determination of Intracellular CaBio-protocol · 2020Article
- SQ109 inhibits proliferation of Leishmania donovani by disruption of intracellular CaParasitology research · 2020Article
- Disruption of Intracellular Calcium Homeostasis as a Therapeutic Target AgainstFrontiers in cellular and infection microbiology · 2020Review
- Withdrawal of prenylamine: perspectives on pharmacological, clinical and regulatory outcomes following the first QT-related casualty.Therapeutic advances in drug safety · 2018Review
- Repurposing as a strategy for the discovery of new anti-leishmanials: the-state-of-the-art.Parasitology · 2018Review
- Activity of the antiarrhythmic drug amiodarone againstThe journal of venomous animals and toxins including tropical diseases · 2018Article
- Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane CaAntimicrobial agents and chemotherapy · 2018Article
- Inhibition of Leishmania mexicana Growth by the Tuberculosis Drug SQ109.Antimicrobial agents and chemotherapy · 2016Article
- Antiinfectives targeting enzymes and the proton motive force.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal CaMicrobial cell (Graz, Austria) · 2015Article
- Leishmania major telomerase TERT protein has a nuclear/mitochondrial eclipsed distribution that is affected by oxidative stress.Infection and immunity · 2015Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Dronedarone and amiodarone are cationic lipophilic benzofurans used to treat cardiac arrhythmias. They also have activity against the parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas' disease. They function by disrupting intracellular Ca2+ homeostasis of the parasite and by inhibiting membrane sterol (ergosterol) biosynthesis. Amiodarone also has activity against Leishmania mexicana, suggesting that dronedarone might likewise be active against this organism. This might be of therapeutic interest, since dronedarone is thought to have fewer side effects in humans than does amiodarone. We show here that dronedarone effectively inhibits the growth of L. mexicana promastigotes in culture and, more importantly, has excellent activity against amastigotes inside infected macrophages (the clinically relevant form) without affecting the host cell, with the 50% inhibitory concentrations against amastigotes being 3 orders of magnitude lower than those obtained previously with T. cruzi amastigotes (0.65 nM versus 0.75 μM). As with amiodarone, dronedarone affects intracellular Ca2+ homeostasis in the parasite, inducing an elevation of intracellular Ca2+ levels. This is achieved by rapidly collapsing the mitochondrial membrane potential and inducing an alkalinization of acidocalcisomes at a rate that is faster than that observed with amiodarone. We also show that dronedarone inhibits parasite oxidosqualene cyclase, a key enzyme in ergosterol biosynthesis known to be vital for survival. Overall, our results suggest the possibility of repurposing dronedarone as a treatment for cutaneous, and perhaps other, leishmaniases.
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Registered trials
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.