ArticleScientific reports2017
Novel scaffolds for inhibition of Cruzipain identified from high-throughput screening of anti-kinetoplastid chemical boxes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Discovery of Novel Inhibitors of Cruzain Cysteine Protease ofCurrent medicinal chemistry · 2024Pooled it
- Cystatin from Austrelaps superbus snake venom as a model for identifying potential inhibitors of Trypanosoma cruzi cruzain.The journal of venomous animals and toxins including tropical diseases · 2025Article
- Repurposing of rabeprazole as an anti-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Thio- and selenosemicarbazones as antiprotozoal agents againstJournal of enzyme inhibition and medicinal chemistry · 2022Article
- Repurposing the Trypanosomatidic GSK Kinetobox for the Inhibition of Parasitic Pteridine and Dihydrofolate Reductases.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Structural Optimization and Biological Activity of Pyrazole Derivatives: Virtual Computational Analysis, Recovery Assay and 3D Culture Model as Potential Predictive Tools of Effectiveness againstMolecules (Basel, Switzerland) · 2021Article
- Screening and Identification of Metacaspase Inhibitors: Evaluation of Inhibition Mechanism and Trypanocidal Activity.Antimicrobial agents and chemotherapy · 2021Article
- Towards discovery of new leishmanicidal scaffolds able to inhibitJournal of enzyme inhibition and medicinal chemistry · 2020Article
- Chagas Disease: Perspectives on the Past and Present and Challenges in Drug Discovery.Molecules (Basel, Switzerland) · 2020Review
- Nanotechnological interventions for treatment of trypanosomiasis in humans and animals.Drug delivery and translational research · 2020Article
- Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning.Biomolecules · 2020Review
- Current trends in the pharmacological management of Chagas disease.International journal for parasitology. Drugs and drug resistance · 2020Review
- Carbamoyl-RSC advances · 2020Article
- Advances in preclinical approaches to Chagas disease drug discovery.Expert opinion on drug discovery · 2019Review
- Discovery and characterization of trypanocidal cysteine protease inhibitors from the 'malaria box'.European journal of medicinal chemistry · 2019Article
- Potent and selective inhibitors for M32 metallocarboxypeptidases identified from high-throughput screening of anti-kinetoplastid chemical boxes.PLoS neglected tropical diseases · 2019Article
- Discovery of Non-Peptidic Compounds against Chagas Disease Applying Pharmacophore Guided Molecular Modelling Approaches.Molecules (Basel, Switzerland) · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
American Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T. cruzi, is an important virulence factor and a chemotherapeutic target with excellent pre-clinical validation evidence. Here, we present the identification of new Cruzipain inhibitory scaffolds within the GlaxoSmithKline HAT (Human African Trypanosomiasis) and Chagas chemical boxes, two collections grouping 404 non-cytotoxic compounds with high antiparasitic potency, drug-likeness, structural diversity and scientific novelty. We have adapted a continuous enzymatic assay to a medium-throughput format and carried out a primary screening of both collections, followed by construction and analysis of dose-response curves of the most promising hits. Using the identified compounds as a starting point a substructure directed search against CHEMBL Database revealed plausible common scaffolds while docking experiments predicted binding poses and specific interactions between Cruzipain and the novel inhibitors.
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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.