Abstract
Human African trypanosomiasis and Chagas disease are the main causes of heart failure in developing countries. The disadvantages of current therapy include: undesirable side-effects, resistance, lack of efficacy on late-stage disease and lack of pediatric formulations. Efforts to find new compound hits have spanned SAR studies to very high-throughput and virtual screens and drug repurposing. The integrated analysis of these strategies on the discovery of anti-Chagas agents is timely. This work accounts for the progress on the development of cruzain inhibitors following these avenues, with emphasis on structural aspects of the ligand-cruzain recognition process.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Chagas Cardiomyopathy / drug therapy*
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Chagas Cardiomyopathy / parasitology
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Computer-Aided Design
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Cysteine Endopeptidases / chemistry
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Cysteine Endopeptidases / metabolism
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Drug Design*
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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High-Throughput Screening Assays
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Humans
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Ligands
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Molecular Docking Simulation
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Molecular Structure
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Protozoan Proteins / antagonists & inhibitors*
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Protozoan Proteins / chemistry
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Protozoan Proteins / metabolism
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Structure-Activity Relationship
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Trypanocidal Agents / chemistry*
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Trypanocidal Agents / pharmacology
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Trypanosoma brucei brucei / drug effects*
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Trypanosoma brucei brucei / enzymology
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Trypanosoma cruzi / drug effects*
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Trypanosoma cruzi / enzymology
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Trypanosomiasis, African / drug therapy*
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Trypanosomiasis, African / parasitology
Substances
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Enzyme Inhibitors
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Ligands
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Protozoan Proteins
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Trypanocidal Agents
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Cysteine Endopeptidases
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cruzain, Trypanosoma cruzi