Abstract
Chagas disease or American trypanosomiasis is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. The chemotherapy drugs currently used are limited to benznidazole and nifurtimox. They are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenting drawbacks during the treatment. Thus, there is an urgent need for new effective, safe and affordable drugs to fight against this complex disease. There were high expectations for azole derivatives as they appeared to be the most promising drugs for the treatment of Chagas disease during the last decade; however, the disappointing results obtained so far in clinical trials evidenced the lack of correlation between preclinical and clinical development. Therefore, the feedback obtained from these studies should define the starting point for addressing a roadmap for the drug discovery process in the fight against this disease. To tackle this challenge, it is important to keep in mind the drug target profile, already defined by panels of experts, and the coordinated work involving multi-disciplinary networks focusing not only on the discovery of new drugs but also on the standardization of the protocols that would allow acceleration in the Chagas disease drug discovery process.
Keywords: Chagas disease, Trypanosoma cruzi, drug discovery, screening cascade, clinical trials, target product profile, neglected tropical disease.
Current Medicinal Chemistry
Title:Challenges in Chagas Disease Drug Discovery: A Review
Volume: 23 Issue: 28
Author(s): Rocio Paucar, Elsa Moreno-Viguri and Silvia Pérez-Silanes
Affiliation:
Keywords: Chagas disease, Trypanosoma cruzi, drug discovery, screening cascade, clinical trials, target product profile, neglected tropical disease.
Abstract: Chagas disease or American trypanosomiasis is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Although the number of infected individuals has decreased, about 6-7 million people are infected worldwide. The chemotherapy drugs currently used are limited to benznidazole and nifurtimox. They are effective in acute phase, congenital transmission and children with chronic infection; however, recent clinical trials have shown limitations in adults with chronic infection, presenting drawbacks during the treatment. Thus, there is an urgent need for new effective, safe and affordable drugs to fight against this complex disease. There were high expectations for azole derivatives as they appeared to be the most promising drugs for the treatment of Chagas disease during the last decade; however, the disappointing results obtained so far in clinical trials evidenced the lack of correlation between preclinical and clinical development. Therefore, the feedback obtained from these studies should define the starting point for addressing a roadmap for the drug discovery process in the fight against this disease. To tackle this challenge, it is important to keep in mind the drug target profile, already defined by panels of experts, and the coordinated work involving multi-disciplinary networks focusing not only on the discovery of new drugs but also on the standardization of the protocols that would allow acceleration in the Chagas disease drug discovery process.
Export Options
About this article
Cite this article as:
Paucar Rocio, Moreno-Viguri Elsa and Pérez-Silanes Silvia, Challenges in Chagas Disease Drug Discovery: A Review, Current Medicinal Chemistry 2016; 23 (28) . https://dx.doi.org/10.2174/0929867323999160625124424
DOI https://dx.doi.org/10.2174/0929867323999160625124424 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
New Insights into the Role of FGF-23 and Klotho in Cardiovascular Disease in Chronic Kidney Disease Patients
Current Vascular Pharmacology Cell Sheet-Based Myocardial Tissue Engineering: New Hope for Damaged Heart Rescue
Current Pharmaceutical Design Cardiovascular Effects of EGFR (Epidermal Growth Factor Receptor) Monoclonal Antibodies
Cardiovascular & Hematological Agents in Medicinal Chemistry Patent Selections:
Recent Patents on Cardiovascular Drug Discovery Study of Parasitic Infections, Cancer, and other Diseases with Mass-Spectrometry and Quantitative Proteome-Disease Relationships
Current Proteomics Refractory Angina Pectoris: Lessons from the Past and Current Perspectives
Current Pharmaceutical Design Repositioning of Drugs in Cardiometabolic Disorders: Importance and Current Scenario
Current Topics in Medicinal Chemistry The Small Heat Shock Protein HspB8: Role in Nervous System Physiology and Pathology
CNS & Neurological Disorders - Drug Targets Free Fatty Acids: Circulating Contributors of Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Cardiovascular Effects of Neuregulin-1/ErbB Signaling: Role in Vascular Signaling and Angiogenesis
Current Pharmaceutical Design Selective Inhibition of Phosphodiesterases 4A, B, C and D Isoforms in Chronic Respiratory Diseases: Current and Future Evidences
Current Pharmaceutical Design Stem Cell-Derived Microvesicles: A Cell Free Therapy Approach to the Regenerative Medicine
Current Biotechnology New Perspectives of Infections in Cardiovascular Disease
Current Cardiology Reviews Chromogranins and Inositol 1,4,5-Trisphosphate-Dependent Ca2+-Signaling in Cardiomyopathy and Heart Failure
Current Medicinal Chemistry Role of Chymase in Preeclampsia
Current Vascular Pharmacology Rheumatoid Arthritis: Cardiovascular Manifestations, Pathogenesis, and Therapy
Current Pharmaceutical Design Atrial Fibrillation with a Focus on Oral Antiarrhythmic Therapy
Current Drug Therapy Molecular Signature of Human amniotic Fluid Stem Cells During Fetal Development
Current Stem Cell Research & Therapy Altered Calmodulin Degradation and Signaling in Non-Neuronal Cells from Alzheimer’s Disease Patients
Current Alzheimer Research Old and New Gasotransmitters in the Cardiovascular System: Focus on the Role of Nitric Oxide and Hydrogen Sulfide in Endothelial Cells and Cardiomyocytes
Current Pharmaceutical Biotechnology