Abstract
The protozoan parasites, Trypanosoma brucei and T. cruzi, that cause sleeping sickness in sub-Saharan Africa and Chagas Disease in Latin America, respectively, exert significant morbidity and mortality in man. Combinations of toxicity and differential efficacy of current drugs provide an urgent need to develop novel, cheap and effective chemotherapies. Research over the last decade with cultured trypanosomes and mice experimentally infected with these parasites has demonstrated that trypanosome cysteine proteinases are valid targets for the rational design of new drugs. In particular, potent peptidyl and peptidomimetic inhibitors of brucipain (a.k.a. trypanopain-Tb) and cruzain (a.k.a. cruzipain), the respective cysteine proteinases of T. brucei and T. cruzi, have proved trypanocidal. Efforts are ongoing to develop more specific non-toxic inhibitors of various chemistries with improved biological half-lives and biovailability characteristics. Here, the biochemical and biological properties together with the history, current status and perceived directions on the development of specific inhibitors of trypanosome cysteine proteinases will be reviewed.
Keywords: September 2000, Protozoan Parasites, Trypanosma brucei, Plasmodium, Leishmania, T conglense, Cathepsin, Cysteine proteinase Inhibitors
Current Drug Targets
Title: Cysteine Proteinases of Trypanosome Parasites Novel Targets for Chemotherapy
Volume: 1 Issue: 2
Author(s): C. R. Caffrey, S. Scory and D. Steverding
Affiliation:
Keywords: September 2000, Protozoan Parasites, Trypanosma brucei, Plasmodium, Leishmania, T conglense, Cathepsin, Cysteine proteinase Inhibitors
Abstract: The protozoan parasites, Trypanosoma brucei and T. cruzi, that cause sleeping sickness in sub-Saharan Africa and Chagas Disease in Latin America, respectively, exert significant morbidity and mortality in man. Combinations of toxicity and differential efficacy of current drugs provide an urgent need to develop novel, cheap and effective chemotherapies. Research over the last decade with cultured trypanosomes and mice experimentally infected with these parasites has demonstrated that trypanosome cysteine proteinases are valid targets for the rational design of new drugs. In particular, potent peptidyl and peptidomimetic inhibitors of brucipain (a.k.a. trypanopain-Tb) and cruzain (a.k.a. cruzipain), the respective cysteine proteinases of T. brucei and T. cruzi, have proved trypanocidal. Efforts are ongoing to develop more specific non-toxic inhibitors of various chemistries with improved biological half-lives and biovailability characteristics. Here, the biochemical and biological properties together with the history, current status and perceived directions on the development of specific inhibitors of trypanosome cysteine proteinases will be reviewed.
Export Options
About this article
Cite this article as:
Caffrey R. C., Scory S. and Steverding D., Cysteine Proteinases of Trypanosome Parasites Novel Targets for Chemotherapy, Current Drug Targets 2000; 1 (2) . https://dx.doi.org/10.2174/1389450003349290
DOI https://dx.doi.org/10.2174/1389450003349290 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read 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
Related Articles
-
The Role of Coronary Angioplasty in the Management of Patients with Stable Coronary Artery Disease
Cardiovascular & Hematological Disorders-Drug Targets Antiapoptotic Effect of Novel Compound from Herba leonuri-Leonurine (SCM-198): A Mechanism Through Inhibition of Mitochondria Dysfunction in H9c2 Cells
Current Pharmaceutical Biotechnology Ivabradine: The Hope for a Good Treatment of Ischemic Heart Disease
Current Medicinal Chemistry Prevention and Therapeutic Strategies of Thromboembolic Events in Patients with Inflammatory Bowel Diseases: A Report of Three Cases
Current Drug Targets A Critical Approach of Guideline Therapeutic Recommendations for NAFLD
Current Vascular Pharmacology Binding Interactions of Forskolin with Human Serum Albumin: Insights from In silico and Spectroscopic Studies
Current Chemical Biology Recent Advances in the Oral Delivery of Insulin
Recent Patents on Drug Delivery & Formulation 1,8-Naphthyridine Derivatives: A Privileged Scaffold for Versatile Biological Activities
Mini-Reviews in Medicinal Chemistry Vitamin D3, D2 and Arterial Wall Properties in Coronary Artery Disease
Current Pharmaceutical Design Molecular Mechanisms of Skeletal Muscle Insulin Resistance in Type 2 Diabetes
Current Diabetes Reviews Is Programmed Aging a Cause for Optimism?
Current Aging Science Challenges of Stem-cell-based Craniofacial Regeneration
Current Stem Cell Research & Therapy Fatty Acids and Obesity
Current Pharmaceutical Design Neuroprotective Effects of Quercetin: From Chemistry to Medicine
CNS & Neurological Disorders - Drug Targets The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin
Current Vascular Pharmacology Approaches to Target Profiling of Natural Products
Current Medicinal Chemistry Cell Adhesion Molecules as Pharmaceutical Target in Atherosclerosis
Mini-Reviews in Medicinal Chemistry Aortic Stenosis, Aortic Regurgitation and Arterial Hypertension
Current Vascular Pharmacology Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases
Current Neuropharmacology Chronic Obstructive Pulmonary Disease and Asthma and the Risk of Mild Cognitive Impairment and Dementia: A Population Based CAIDE Study
Current Alzheimer Research