Abstract
There is a high demand for new drugs against malaria, which takes millions of lives annually. The abuse of classical antimalarials from the late 1940's to the early 1980's has bred resistant parasites, which led to the use of more potent drugs that ended up by refueling the resistance cycle. An example is chloroquine, once highly effective but now virtually useless against malaria.
Structure-based rational drug design relies on high-resolution target structures to allow for screening of selective ligands/inhibitors. For the past two decades, and especially after the unveiling of the Plasmodium falciparum genome in 2002, enzymes of this lethal malaria parasite species have been increasingly attracting the attention of Medicinal Chemists worldwide as promising drug targets. There is particular emphasis on proteases having key roles on the degradation of host's hemoglobin within the food vacuole of blood-stage parasites, as these depend on such process for their survival. Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets. The present review will focus on the computational approaches made so far towards the unraveling of the structure, function and inhibition of Falcipains that, by virtue of their quite specific features, are excellent targets for highly selective inhibitors.
Keywords: Cysteine proteases, drug design, falcipain inhibitors, falcipains, malaria, Plasmodium Falciparum, classical antimalarials, resistant parasites, chloroquine
Current Medicinal Chemistry
Title: Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria
Volume: 18 Issue: 10
Author(s): C. Teixeira, J. R.B. Gomes and P. Gomes
Affiliation:
Keywords: Cysteine proteases, drug design, falcipain inhibitors, falcipains, malaria, Plasmodium Falciparum, classical antimalarials, resistant parasites, chloroquine
Abstract: There is a high demand for new drugs against malaria, which takes millions of lives annually. The abuse of classical antimalarials from the late 1940's to the early 1980's has bred resistant parasites, which led to the use of more potent drugs that ended up by refueling the resistance cycle. An example is chloroquine, once highly effective but now virtually useless against malaria.
Structure-based rational drug design relies on high-resolution target structures to allow for screening of selective ligands/inhibitors. For the past two decades, and especially after the unveiling of the Plasmodium falciparum genome in 2002, enzymes of this lethal malaria parasite species have been increasingly attracting the attention of Medicinal Chemists worldwide as promising drug targets. There is particular emphasis on proteases having key roles on the degradation of host's hemoglobin within the food vacuole of blood-stage parasites, as these depend on such process for their survival. Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets. The present review will focus on the computational approaches made so far towards the unraveling of the structure, function and inhibition of Falcipains that, by virtue of their quite specific features, are excellent targets for highly selective inhibitors.
Export Options
About this article
Cite this article as:
Teixeira C., R.B. Gomes J. and Gomes P., Falcipains, Plasmodium falciparum Cysteine Proteases as Key Drug Targets Against Malaria, Current Medicinal Chemistry 2011; 18 (10) . https://dx.doi.org/10.2174/092986711795328328
DOI https://dx.doi.org/10.2174/092986711795328328 |
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
-
Kynurenines in the Central Nervous System: Recent Developments
Central Nervous System Agents in Medicinal Chemistry Ameliorative Effect of Trans-Sinapic Acid and its Protective Role in Cerebral Hypoxia in Aluminium Chloride Induced Dementia of Alzheimer's Type
CNS & Neurological Disorders - Drug Targets Patent Selections
Recent Patents on DNA & Gene Sequences Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology
Current Neuropharmacology Patent Selections:
Recent Patents and Topics on Imaging (Discontinued) Wnt Signaling and Cell-Matrix Adhesion
Current Molecular Medicine Hypertension Impairs Cerebral Blood Flow in a Mouse Model for Alzheimer’s Disease
Current Alzheimer Research Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry An Osteoblastic Inflammatory Redox Model, using TNF-a, Glucose and Glucose- Oxidized Low- Density Lipoprotein: Targets for Minocycline
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Identification of Differentially Expressed Hematopoiesis-associated Genes in Term Low Birth Weight Newborns by Systems Genomics Approach
Current Genomics Polyphenols: Well Beyond The Antioxidant Capacity: Gallic Acid and Related Compounds as Neuroprotective Agents: You are What You Eat!
Current Pharmaceutical Biotechnology Screening for Amyloid Aggregation: In-Silico, In-Vitro and In-Vivo Detection
Current Protein & Peptide Science Overlooked Issues of Snakebite Management: Time for Strategic Approach
Current Topics in Medicinal Chemistry Leptin and the Ob-Receptor as Anti-Obesity Target: Recent In Silico Advances in the Comprehension of the Protein-Protein Interaction and Rational Drug Design of Anti- Obesity Lead Compounds
Current Pharmaceutical Design Analysis of Adverse Events Related to 720 Cases of Neural Progenitor Cell Transplantation
CNS & Neurological Disorders - Drug Targets Targeting Ion Channels for New Strategies in Cancer Diagnosis and Therapy
Current Clinical Pharmacology Herb-drug Interactions Involving Drug Metabolizing Enzymes and Transporters
Current Drug Metabolism Structural Basis of Agonist Selectivity for Different nAChR Subtypes: Insights from Crystal Structures, Mutation Experiments and Molecular Simulations
Current Pharmaceutical Design Inflammation, Hyperinflammation & Cystic Fibrosis Lung Disease – A Paradigm Shift?
Current Respiratory Medicine Reviews Multitasking of Neuropeptide Y through the Lens of Motifs
Recent Patents on CNS Drug Discovery (Discontinued)