Abstract
One of the most neglected disease is the Sleeping sickness or Human African Trypanosomiasis (HAT), which is mostly restricted to poor regions of Africa. The disease is caused by parasitic infection with Trypanosoma brucei (T. brucei), and is acquired through the bite of the tsetse fly. In the first stage of the disease, the parasite is in the blood, but in stage 2, the infective form reaches the brain, causing great weakness and death. The few existing drugs against this infection, are highly toxic, and can cause the emergence of resistant forms of the parasite. Also, these drugs are not readily available. New drugs are needed. Many researchers are investigating new enzyme targets for the parasite, searching for more efficient and selective inhibitors that are capable to cause the parasite death with less toxicity to the host. Trypanothione reductase, farnesyl diphosphate synthase, 6-phospho-gluconate dehydrogenase, and UDP 4'-galactose epimerase are some of the enzymes involved in the studies reported on this review. In addition, we have applied ligandbased- virtual screening, using Random Forest associated with structure-based-virtual screening (docking), to a small dataset of 225 alkaloids from the Menispermaceae family (in-house data bank). The aim of this study is to select structures with potential inhibitory activity against trypanothione reductase from Trypanosoma brucei. The computer-aided drug design study selected certain alkaloids that might be worth further investigation.
Keywords: Sleeping sickness, T. brucei, enzyme, docking, trypanothione reductase, target.
Current Protein & Peptide Science
Title:Enzymatic Targets in Trypanosoma brucei
Volume: 17 Issue: 3
Author(s): Luciana Scotti, Francisco J.B. Mendonça, Marcelo S. da Silva and Marcus T. Scotti
Affiliation:
Keywords: Sleeping sickness, T. brucei, enzyme, docking, trypanothione reductase, target.
Abstract: One of the most neglected disease is the Sleeping sickness or Human African Trypanosomiasis (HAT), which is mostly restricted to poor regions of Africa. The disease is caused by parasitic infection with Trypanosoma brucei (T. brucei), and is acquired through the bite of the tsetse fly. In the first stage of the disease, the parasite is in the blood, but in stage 2, the infective form reaches the brain, causing great weakness and death. The few existing drugs against this infection, are highly toxic, and can cause the emergence of resistant forms of the parasite. Also, these drugs are not readily available. New drugs are needed. Many researchers are investigating new enzyme targets for the parasite, searching for more efficient and selective inhibitors that are capable to cause the parasite death with less toxicity to the host. Trypanothione reductase, farnesyl diphosphate synthase, 6-phospho-gluconate dehydrogenase, and UDP 4'-galactose epimerase are some of the enzymes involved in the studies reported on this review. In addition, we have applied ligandbased- virtual screening, using Random Forest associated with structure-based-virtual screening (docking), to a small dataset of 225 alkaloids from the Menispermaceae family (in-house data bank). The aim of this study is to select structures with potential inhibitory activity against trypanothione reductase from Trypanosoma brucei. The computer-aided drug design study selected certain alkaloids that might be worth further investigation.
Export Options
About this article
Cite this article as:
Scotti Luciana, J.B. Mendonça Francisco, S. da Silva Marcelo and T. Scotti Marcus, Enzymatic Targets in Trypanosoma brucei, Current Protein & Peptide Science 2016; 17 (3) . https://dx.doi.org/10.2174/1389203717999160226173754
DOI https://dx.doi.org/10.2174/1389203717999160226173754 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
-
Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside
Current Vascular Pharmacology Cardiovascular Diseases in Pregnancy - A Brief Overview
Current Cardiology Reviews Developing Histone Deacetylase Inhibitors as Anti-Cancer Therapeutics
Current Medicinal Chemistry Admission, 24 Hours and Discharge Troponin T Among Acute Myocardial Infarction Patients: Differing by Prognostic Contribution
Recent Patents on Biomarkers Sigma Receptor Activation Reduces Infarct Size at 24 Hours After Permanent Middle Cerebral Artery Occlusion in Rats
Current Neurovascular Research Irreversible Inhibition of Serine Proteases – Design and In Vivo Activity of Diaryl α-Aminophosphonate Derivatives
Current Medicinal Chemistry Design and Evaluation of HP-β-CD Based Voriconazole Formulations for Ocular Drug Delivery
Current Drug Delivery Physiologic Responses in Anxiety
Current Psychiatry Reviews Surgical Ventricular Restoration: An Operation To Reverse Remodeling - The Basic Science (Part I)
Current Cardiology Reviews The Role of Brain Gaseous Transmitters in the Regulation of the Circulatory System
Current Pharmaceutical Biotechnology Cardioprotection by Targeting the Pool of Resident and Extracardiac Progenitors
Current Drug Targets Effects of Tea Catechins on Inflammation-Related Cardiovascular Diseases
Current Immunology Reviews (Discontinued) Role of Molecular Analysis After Autopsy Negative Sudden Death in the Young
Current Pediatric Reviews Role of Tissue Renin-angiotensin System and the Chymase/angiotensin-( 1-12) Axis in the Pathogenesis of Diabetic Retinopathy
Current Medicinal Chemistry Herbal and Traditional Chinese Medicine for the Treatment of Cardiovascular Complications in Diabetes Mellitus
Current Diabetes Reviews Treatment of the Cheyne-Stokes Breathing Pattern in Patients with Congestive Heart Failure: State of the Art
Current Respiratory Medicine Reviews Trypanocidal Activity of Nitroaromatic Prodrugs: Current Treatments and Future Perspectives
Current Topics in Medicinal Chemistry Heart Failure in North America
Current Cardiology Reviews Modulation of Cellular Response to Anticancer Treatment by Caffeine: Inhibition of Cell Cycle Checkpoints, DNA Repair and More
Current Pharmaceutical Biotechnology Diltiazem Analogues: The Last Ten Years on Structure Activity Relationships
Current Medicinal Chemistry