Abstract
Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.
Keywords: Drug targets, glycolysis, metabolism, protozoa, therapeutics.
Current Medicinal Chemistry
Title:Targeting Protozoan Parasite Metabolism: Glycolytic Enzymes in the Therapeutic Crosshairs
Volume: 21 Issue: 15
Author(s): M.T. Harris, W.G. Mitchell and J.C. Morris
Affiliation:
Keywords: Drug targets, glycolysis, metabolism, protozoa, therapeutics.
Abstract: Glycolysis is an important metabolic pathway for most organisms, including protozoan parasites. Many of these primitive eukaryotes have streamlined their metabolism, favoring glycolysis for generating ATP in the glucose-rich environments in which they reside. Therefore, the enzymes involved in hexose metabolism could prove to be attractive targets for therapeutic development. This hypothesis is supported by a number of chemical and genetic validation studies. Additionally, the peculiar biochemistry of many of the components, along with limited protein sequence identity emphasizes the likelihood of developing compounds that selectively inhibit the parasite enzymes. In this review, we examine the status of target validation at the genetic and/or chemical levels from the protozoan parasites. While the proteins from some species have been interrogated to the point that well-defined lead compounds have been identified with activities against both enzyme and parasite growth, progress in other systems has to date been limited.
Export Options
About this article
Cite this article as:
Harris M.T., Mitchell W.G. and Morris J.C., Targeting Protozoan Parasite Metabolism: Glycolytic Enzymes in the Therapeutic Crosshairs, Current Medicinal Chemistry 2014; 21 (15) . https://dx.doi.org/10.2174/09298673113206660286
DOI https://dx.doi.org/10.2174/09298673113206660286 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
The Many Roles of Chemokine Receptors in Neurodegenerative Disorders: Emerging New Therapeutical Strategies
Current Medicinal Chemistry Isatin Derivatives and Their Antiviral Properties Against Arboviruses: A Review
Mini-Reviews in Medicinal Chemistry Protein Kinase CK2 in Human Diseases
Current Medicinal Chemistry Extracellular Vesicles as Novel Delivery Tools for Cancer Treatment
Current Cancer Drug Targets Medicinal and Therapeutic Potential of Herbs and Plant Metabolites / Extracts Countering Viral Pathogens - Current Knowledge and Future Prospects
Current Drug Metabolism BACE1 Levels Correlate with Phospho-Tau Levels in Human Cerebrospinal Fluid
Current Alzheimer Research Abeta DNA Vaccination for Alzheimers Disease: Focus on Disease Prevention
CNS & Neurological Disorders - Drug Targets Opiate Addiction Therapies and HIV-1 Tat: Interactive Effects on Glial [Ca<sup>2+</sup>]<sub>i</sub>, Oxyradical and Neuroinflammatory Chemokine Production and Correlative Neurotoxicity
Current HIV Research Conventional (Continuous) EEG Monitoring in the NICU
Current Pediatric Reviews Strain Typing of Mycoplasma pneumoniae and its Value in Epidemiology
Current Pediatric Reviews Heparan Sulphate Proteoglycans and Viral Vectors : Ally or Foe?
Current Gene Therapy Small-molecule Antiviral Agents in Ongoing Clinical Trials for COVID-19
Current Drug Targets Aptamers: Selection, Modification and Application to Nervous System Diseases
Current Medicinal Chemistry Oncolytic HSV-1 Virotherapy: Clinical Experience and Opportunities for Progress
Current Pharmaceutical Biotechnology Tofacitinib-induced Ramsay- Hunt Syndrome in a Patient with Rheumatoid Arthritis
Current Drug Safety Rationale for Peptide and DNA Based Epitope Vaccines for Alzheimers Disease Immunotherapy
CNS & Neurological Disorders - Drug Targets Inflammation and Age-Related Iron Accumulation in F344 Rats
Current Aging Science The New Immunosuppression: Intervention at the Dendritic Cell-T-Cell Interface
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Heat Shock Proteins And Neuroprotection
Recent Patents on DNA & Gene Sequences Natural Products as a Paradigm for the Treatment of Coxsackievirus - induced Myocarditis
Current Topics in Medicinal Chemistry