ArticleScientific reports2015
Structure-based discovery of the first non-covalent inhibitors of Leishmania major tryparedoxin peroxidase by high throughput docking.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 63 citations in OpenAlex.
- Cross-Species Hepatic Metabolism of the Antileishmanial Chalcone NAT22 Generates Metabolites with Predicted Enhanced Affinity for the Parasite Target cTXNPx.Pharmaceutics · 2026Article
- Screening of the antileishmanial and antiplasmodial potential of synthetic 2-arylquinoline analogs.Scientific reports · 2023Article
- Pharmacophoric analogs of sotorasib-entrapped KRAS G12C in its inactive GDP-bound conformation: covalent docking and molecular dynamics investigations.Molecular diversity · 2023Article
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- Disruption of Irisin Dimerization by FDA-Approved Drugs: A Computational Repurposing Approach for the Potential Treatment of Lipodystrophy Syndromes.International journal of molecular sciences · 2023Article
- Article
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Integrated virtual screening and molecular dynamics simulation revealed promising drug candidates of p53-MDM2 interaction.Journal of molecular modeling · 2022Article
- Total Synthesis of the Natural Chalcone Lophirone E, Synthetic Studies toward Benzofuran and Indole-Based Analogues, and Investigation of Anti-Leishmanial Activity.Molecules (Basel, Switzerland) · 2022Article
- Chalcones identify cTXNPx as a potential antileishmanial drug target.PLoS neglected tropical diseases · 2021Article
- A Repurposing Approach for Uncovering the Anti-Tubercular Activity of FDA-Approved Drugs with Potential Multi-Targeting Profiles.Molecules (Basel, Switzerland) · 2019Article
- Computational Approaches for Drug Discovery.Molecules (Basel, Switzerland) · 2019Article
- Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening.PLoS neglected tropical diseases · 2018Article
- Chemoinformatics Strategies for Leishmaniasis Drug Discovery.Frontiers in pharmacology · 2018Review
- Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions.PLoS neglected tropical diseases · 2017Article
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Authors and funding
13 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Leishmaniasis is a neglected vector-born disease caused by a protozoan of the genus Leishmania and affecting more than 1.300.000 people worldwide. The couple tryparedoxin/tryparedoxin peroxidase is essential for parasite survival in the host since it neutralizes the hydrogen peroxide produced by macrophages during the infection. Herein we report a study aimed at discovering the first class of compounds able to non-covalently inhibit tryparedoxin peroxidase. We have solved the high-resolution structure of Tryparedoxin peroxidase I from Leishmania major (LmTXNPx) in the reduced state and in fully folded conformation. A first series of compounds able to inhibit LmTXNPx was identified by means of the high throughput docking technique. The inhibitory activity of these compounds was validated by a Horseradish peroxidase-based enzymatic assay and their affinity for LmTXNPx calculated by surface plasmon resonance experiments. On the basis of these results, the analysis of the enzyme-inhibitor docked models allowed us to rationally design and synthesize a series of N,N-disubstituted 3-aminomethyl quinolones. These compounds showed an inhibitory potency against LmTXNPx in the micromolar range. Among them, compound 12 represents the first non-covalent LmTXNPx inhibitor reported to date and could pave the way to the discovery of a new class of drugs against leishmaniasis.
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