Abstract
Malaria is a leading cause of morbidity and mortality in the tropics. Chemotherapeutic and vector control strategies have been applied for more than a century but have not been efficient in disease eradication. Increased resistance of malaria parasites to drug treatment and of mosquito vectors to insecticides requires the development of novel chemotherapeutic agents. Malaria parasites exhibit rapid nucleic acid synthesis during their intraerythrocytic growth phase. Plasmodium purine and pyrimidine metabolic pathways are distinct from those of their human hosts. Thus, targeting purine and pyrimidine metabolic pathways provides a promising route for novel drug development. Recent developments in enzymatic transition state analysis have provided an improved route to inhibitor design targeted to specific enzymes, including those of purine and pyrimidine metabolism. Modern transition state analogue drug discovery has resulted in transition state analogues capable of binding to target enzymes with unprecedented affinity and specificity. These agents can provide specific blocks in essential pathways. The combination of tight binding with the high specificity of these logically designed inhibitors, results in low toxicity and minor side effects. These features reduce two of the major problems with the current antimalarials. Transition state analogue design is being applied to generate new lead compounds to treat malaria by targeting purine and pyrimidine pathways.
Keywords: Antimalarials, malaria, purines, pyrimidines, transition state analogues, immucillins, Chemotherapeutic and vector control, mosquito vectors, intraerythrocytic growth phase, purine and pyrimidine metabolic pathways, enzymatic transition state analysis, purine and pyrimidine metabolism, drug discovery has, unprecedented affinity specificity, Transition state analogue design
Current Topics in Medicinal Chemistry
Title: Purine and Pyrimidine Pathways as Targets in Plasmodium falciparum
Volume: 11 Issue: 16
Author(s): Maria Belen Cassera, Yong Zhang, Keith Z. Hazleton and Vern L. Schramm
Affiliation:
Keywords: Antimalarials, malaria, purines, pyrimidines, transition state analogues, immucillins, Chemotherapeutic and vector control, mosquito vectors, intraerythrocytic growth phase, purine and pyrimidine metabolic pathways, enzymatic transition state analysis, purine and pyrimidine metabolism, drug discovery has, unprecedented affinity specificity, Transition state analogue design
Abstract: Malaria is a leading cause of morbidity and mortality in the tropics. Chemotherapeutic and vector control strategies have been applied for more than a century but have not been efficient in disease eradication. Increased resistance of malaria parasites to drug treatment and of mosquito vectors to insecticides requires the development of novel chemotherapeutic agents. Malaria parasites exhibit rapid nucleic acid synthesis during their intraerythrocytic growth phase. Plasmodium purine and pyrimidine metabolic pathways are distinct from those of their human hosts. Thus, targeting purine and pyrimidine metabolic pathways provides a promising route for novel drug development. Recent developments in enzymatic transition state analysis have provided an improved route to inhibitor design targeted to specific enzymes, including those of purine and pyrimidine metabolism. Modern transition state analogue drug discovery has resulted in transition state analogues capable of binding to target enzymes with unprecedented affinity and specificity. These agents can provide specific blocks in essential pathways. The combination of tight binding with the high specificity of these logically designed inhibitors, results in low toxicity and minor side effects. These features reduce two of the major problems with the current antimalarials. Transition state analogue design is being applied to generate new lead compounds to treat malaria by targeting purine and pyrimidine pathways.
Export Options
About this article
Cite this article as:
Belen Cassera Maria, Zhang Yong, Z. Hazleton Keith and L. Schramm Vern, Purine and Pyrimidine Pathways as Targets in Plasmodium falciparum, Current Topics in Medicinal Chemistry 2011; 11 (16) . https://dx.doi.org/10.2174/156802611796575948
DOI https://dx.doi.org/10.2174/156802611796575948 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Targeting BMP9-Promoted Human Osteosarcoma Growth by Inactivation of Notch Signaling
Current Cancer Drug Targets Anti-cancer Therapies in High Grade Gliomas
Current Proteomics Cucurbitacins as Inducers of Cell Death and a Rich Source of Potential Anticancer Compounds
Current Pharmaceutical Design Epigenetic Regulation of Epithelial-Mesenchymal Transition by Hypoxia in Cancer: Targets and Therapy
Current Pharmaceutical Design New Strategies in the Discovery of Novel Non-Camptothecin Topoisomerase I Inhibitors
Current Medicinal Chemistry Micro-Nanomaterials for Tumor Microwave Hyperthermia: Design, Preparation, and Application
Current Drug Delivery Developments in the Application of 1,2,3-Triazoles in Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Impact of Nutrients on the Functioning of Intestinal Goblet Cells: Health and Therapeutic Perspectives
Current Nutrition & Food Science Is Effective and Safe a Radiochemotherapy Approach in Elderly Cancer Patients? A Review
Anti-Cancer Agents in Medicinal Chemistry FAK and WNT Signaling: The Meeting of Two Pathways in Cancer and Development
Anti-Cancer Agents in Medicinal Chemistry The Roles of miR-25 and its Targeted Genes in Development of Human Cancer
MicroRNA Prodrugs in Genetic Chemoradiotherapy
Current Pharmaceutical Design Recent Developments in Protein and Cell-Targeted Aptamer Selection and Applications
Current Medicinal Chemistry Prediction of Chemical Multi-target Profiles and Adverse Outcomes with Systems Toxicology
Current Medicinal Chemistry Prospects of Molecularly-Targeted Therapies for Cervical Cancer Treatment
Current Drug Targets MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Ovarian Cancer
Recent Patents on Biomarkers Dual Role of microRNAs in Autophagy of Colorectal Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets The Role of Epidermal Growth Factor Receptor in the Management of Gastrointestinal Carcinomas: Present Status and Future Perspectives
Current Pharmaceutical Design Reversing Aberrant Methylation Patterns in Cancer
Current Medicinal Chemistry Antineoplastic Activity, Structural Modification, Synthesis and Structure-activity Relationship of Dammarane-type Ginsenosides: An Overview
Current Organic Chemistry