ArticleScience translational medicine2012
The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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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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Who cites it
87 citing papers in PubMed, 169 citations in OpenAlex.
- Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies.Clinical pharmacokinetics · 2014Trial
- Orphan Medications: An Innovative and Promising Approach against Leishmaniasis.Current microbiology · 2026Review
- Synthesis and evaluation of nitroheterocyclic aromatic adamantane amides with trypanocidal activity. Part II.RSC medicinal chemistry · 2026Article
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Simultaneous Determination of Fexinidazole and Its Major Metabolites in Rat Plasma by UPLC-MS/MS: Method Validation and Application to Pharmacokinetic Study.Drug design, development and therapy · 2026Article
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Crystallographic and Electroanalytical Analyses of Fexinidazole and Its Major Metabolites.ACS omega · 2025Article
- Mechanistic, in-silico and in vitro studies with nitrofurans reveal potent leishmanicidal activity and inhibition of trypanothione reductase.International journal for parasitology. Drugs and drug resistance · 2025Article
- Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease.Science translational medicine · 2025Article
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Exploring bioactive molecules released during inter- and intraspecific competition: A paradigm for novel antiparasitic drug discovery and design for human use.Current research in parasitology & vector-borne diseases · 2025Review
- Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death inMolecules (Basel, Switzerland) · 2024Article
- Article
- Chemoselective Synthesis and Anti-Kinetoplastidal Properties of 2,6-Diaryl-4Molecules (Basel, Switzerland) · 2024Article
- Phenotypic screening reveals a highly selective phthalimide-based compound with antileishmanial activity.PLoS neglected tropical diseases · 2024Article
- Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.Antimicrobial agents and chemotherapy · 2024Article
- Further Investigations of Nitroheterocyclic Compounds as Potential Antikinetoplastid Drug Candidates.Biomolecules · 2023Review
- Antileishmanial Activities of (Antimicrobial agents and chemotherapy · 2022Article
- Article
- Current Treatments to Control African Trypanosomiasis and One Health Perspective.Microorganisms · 2022Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Safer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50,000 to 60,000 people each year in parts of Asia, Africa, and Latin America. Here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs, and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg/kg) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC(99) (effective concentration inhibiting growth by 99%) value for at least 24 hours after a single oral dose. A once-daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of visceral leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat this tropical disease. In African trypanosomes, the mode of action of nitro drugs involves reductive activation via a NADH (reduced form of nicotinamide adenine dinucleotide)-dependent bacterial-like nitroreductase. Overexpression of the leishmanial homolog of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold, indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating visceral leishmaniasis.
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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.