Abstract
Plasmodium falciparum is responsible for the most severe form of human malaria. P. vivax, in contrast, is the most widespread malaria parasite with an enormous impact on health and economy, since the infection is characterized by high rates of relapses. Due to the mild course of malaria tertiana and complicated in vitro culturing conditions of P. vivax, most of the research on malaria parasites has focused on P. falciparum so far. The redox metabolism of P. falciparum is a promising target for novel antimalarial drugs, since maintaining a redox equilibrium is of fundamental importance for the parasite. P. falciparum contains a cytosolic glutathione and thioredoxin system, as well as redox systems in the apicoplast and the mitochondrion. In contrast to P. falciparum, little is known about the redox processes in P. vivax so far. This review summarizes the current knowledge of the redox metabolism in malaria parasites and provides a detailed in silico comparison of the known and mostly well characterized redox enzymes from P. falciparum and the largely unknown redox proteins from P. vivax. Known antimalarials at least partially mediating their antiparasitic activity by influencing the redox balance of Plasmodium, including dehydroepiandrosterone, Mannich bases, methylene blue, and naphthoquinones, are discussed. Furthermore, we present novel inhibitors identified via screening of a compound library from the Leibniz Institute for Natural Product Research and Infection Biology, Jena that are active against the redox-related enzymes thioredoxin reductase, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase 6- phosphoglucono- lactonase from P. falciparum.
Keywords: Antimalarials, disulfide reductase inhibitors, glutathione, malaria, oxidative stress, Plasmodium vivax, redox metabolism, thioredoxin.
Current Medicinal Chemistry
Title:The Redox Systems of Plasmodium falciparum and Plasmodium vivax: Comparison, In silico Analyses and Inhibitor Studies
Volume: 21 Issue: 15
Author(s): F. Mohring, J. Pretzel, E. Jortzik and K. Becker
Affiliation:
Keywords: Antimalarials, disulfide reductase inhibitors, glutathione, malaria, oxidative stress, Plasmodium vivax, redox metabolism, thioredoxin.
Abstract: Plasmodium falciparum is responsible for the most severe form of human malaria. P. vivax, in contrast, is the most widespread malaria parasite with an enormous impact on health and economy, since the infection is characterized by high rates of relapses. Due to the mild course of malaria tertiana and complicated in vitro culturing conditions of P. vivax, most of the research on malaria parasites has focused on P. falciparum so far. The redox metabolism of P. falciparum is a promising target for novel antimalarial drugs, since maintaining a redox equilibrium is of fundamental importance for the parasite. P. falciparum contains a cytosolic glutathione and thioredoxin system, as well as redox systems in the apicoplast and the mitochondrion. In contrast to P. falciparum, little is known about the redox processes in P. vivax so far. This review summarizes the current knowledge of the redox metabolism in malaria parasites and provides a detailed in silico comparison of the known and mostly well characterized redox enzymes from P. falciparum and the largely unknown redox proteins from P. vivax. Known antimalarials at least partially mediating their antiparasitic activity by influencing the redox balance of Plasmodium, including dehydroepiandrosterone, Mannich bases, methylene blue, and naphthoquinones, are discussed. Furthermore, we present novel inhibitors identified via screening of a compound library from the Leibniz Institute for Natural Product Research and Infection Biology, Jena that are active against the redox-related enzymes thioredoxin reductase, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase 6- phosphoglucono- lactonase from P. falciparum.
Export Options
About this article
Cite this article as:
Mohring F., Pretzel J., Jortzik E. and Becker K., The Redox Systems of Plasmodium falciparum and Plasmodium vivax: Comparison, In silico Analyses and Inhibitor Studies, Current Medicinal Chemistry 2014; 21 (15) . https://dx.doi.org/10.2174/0929867321666131201144612
DOI https://dx.doi.org/10.2174/0929867321666131201144612 |
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
-
PET Designated Flouride-18 Production and Chemistry
Current Topics in Medicinal Chemistry Preclinical Development of Novel Anti-Glioma Drugs Targeting the Endoplasmic Reticulum Stress Response
Current Pharmaceutical Design Development of <sup>18</sup>F-Labeled PET Probes for Imaging Cell Proliferation
Current Topics in Medicinal Chemistry Gene Therapy Approaches to Ataxias
Current Gene Therapy Dietary Phytonutrients in the Prevention of Diabetes-related Complications
Current Diabetes Reviews Inhaled Formulation Design for the Treatment of Lung Infections
Current Pharmaceutical Design Editorial [ Obesity and the Lung Guest Editors: Neil S. Cherniack and E. Paul Cherniack ]
Current Respiratory Medicine Reviews Obsessive-Compulsive Disorder in the Perinatal Period: A Review of the Literature
Current Psychiatry Reviews The Cardiovascular Effects of Metformin: Further Reasons to Consider An Old Drug as a Cornerstone in the Therapy of Type 2 Diabetes Mellitus
Current Vascular Pharmacology Endothelial Nitric Oxide Synthase Gene Therapy for Erectile Dysfunction
Current Pharmaceutical Design Cereal Exposures in the Infant Diet and Risk of Diabetes Autoimmunity in Children
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Reciprocal Interactions Between Wakefulness and Sleep Influence Global and Regional Brain Activity
Current Topics in Medicinal Chemistry Ginkgo biloba Extract 761: A Review of Basic Studies and Potential Clinical Use in Psychiatric Disorders
CNS & Neurological Disorders - Drug Targets Therapeutic Approach on AGE-RAGE Interaction and Its Function in Diabetic Inflammation Process
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Exploring the Potential of NO-Independent Stimulators and Activators of Soluble Guanylate Cyclase for the Medical Treatment of Erectile Dysfunction
Current Pharmaceutical Design Roles of Cardiovascular Risk Factors in Endothelial Nitric Oxide Synthase Regulation: An Update
Current Pharmaceutical Design Natural Products Targeting EGFR Signaling Pathways as Potential Anticancer Drugs
Current Protein & Peptide Science Microdialysis as an Excellent Sampling Approach for Biomedical Analysis
Current Pharmaceutical Analysis Individual Case Safety Reports Analysis for Patients with Diabetes Mellitus on Insulin in Africa and the Middle East
Current Drug Safety Alcoholisms Evolutionary and Cultural Origins
Current Drug Abuse Reviews