ArticlePLoS neglected tropical diseases2018
Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
- Structural basis of ligand selectivity in FAD/NAD(P)H-dependent dehydrogenases: insights from trypanothione reductase and type II NADH dehydrogenase.Protein science : a publication of the Protein Society · 2026Article
- Kinetoplast-Directed Therapies: A Selective Mitochondrial Approach to Combat Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Expanding the Antimicrobial Toolbox with Therapeutic Viruses: Mechanisms, Pharmaceutical Formulation, and Translational Outlook.Pharmaceuticals (Basel, Switzerland) · 2026Review
- In Silico Targeting of Trypanothione Reductase and Glycerol-3-Phosphate Dehydrogenase inMicroorganisms · 2026Article
- PluronicInternational journal of molecular sciences · 2026Article
- Targeting Trypanothione Synthetase and Trypanothione Reductase: Development of Common Inhibitors to Tackle Trypanosomatid Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- High-throughput screening identifies novel chemical scaffolds targeting Leishmania donovani parasites.World journal of microbiology & biotechnology · 2025Article
- Healing and leishmanicidal activity ofFrontiers in chemistry · 2025Article
- Novel Diacyl-hydrazide Compounds as Potential Therapeutics for Visceral Leishmaniasis.ACS omega · 2024Article
- Targeting Trypanothione Metabolism in Trypanosomatids.Molecules (Basel, Switzerland) · 2024Review
- In Silico Exploration of the Trypanothione Reductase (TryR) ofInternational journal of molecular sciences · 2023Article
- ACW-02 an Acridine Triazolidine Derivative Presents Antileishmanial Activity Mediated by DNA Interaction and Immunomodulation.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Inhibition ofMolecules (Basel, Switzerland) · 2023Article
- Immuno-metabolic signaling in leishmaniasis: insights gained from mathematical modeling.Bioinformatics advances · 2023Article
- Probing the Interactions Responsible for the Structural Stability of Trypanothione Reductase Through Computer Simulation and Biophysical Characterization.The protein journal · 2022Article
- Screening of medicinal plants unraveled the leishmanicidal credibility ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Article
- Exploring direct and indirect targets of current antileishmanial drugs using a novel thermal proteomics profiling approach.Frontiers in cellular and infection microbiology · 2022Article
- Innovative Approach for a Classic Target: Fragment Screening on Trypanothione Reductase Reveals New Opportunities for Drug Design.Frontiers in molecular biosciences · 2022Article
- Challenges and Tools for In VitroPathogens (Basel, Switzerland) · 2021Review
- Oral Efficacy of a Diselenide Compound Loaded in Nanostructured Lipid Carriers in a Murine Model of Visceral Leishmaniasis.ACS infectious diseases · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanothione reductase (TR) is considered to be one of the best targets to find new drugs against Leishmaniasis. This enzyme is fundamental for parasite survival in the host since it reduces trypanothione, a molecule used by the tryparedoxin/tryparedoxin peroxidase system of Leishmania to neutralize hydrogen peroxide produced by host macrophages during infection. In order to identify new lead compounds against Leishmania we developed and validated a new luminescence-based high-throughput screening (HTS) assay that allowed us to screen a library of 120,000 compounds. We identified a novel chemical class of TR inhibitors, able to kill parasites with an IC50 in the low micromolar range. The X-ray crystal structure of TR in complex with a compound from this class (compound 3) allowed the identification of its binding site in a pocket at the entrance of the NADPH binding site. Since the binding site of compound 3 identified by the X-ray structure is unique, and is not present in human homologs such as glutathione reductase (hGR), it represents a new target for drug discovery efforts.
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Registered trials
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