Abstract
Cytotoxic nucleoside analogues are clinically important anticancer drugs. These agents behave as antimetabolites, compete with physiologic nucleosides, and, consequently, interact with a large number of intracellular targets to induce cytotoxicity. Nucleoside analogues share some general common characteristics, namely in terms of requiring transport by specific membrane transporters and intracellular metabolism. However these compounds differ in regard to the preferential interaction with certain targets which may explain why some compounds are more effective against rapidly proliferating tumours and others on neoplasia with a more protracted evolution. Purine and pyrimidine analogues are widely used not only as antileukaemic agents, but also as cytotoxic agents to treat solid tumours. However, the clinical use of these compounds is limited by important side-effects and primary or acquired drug resistance. Thus, there is an unmet medical need for the development of new antimetabolites and for technologies allowing a more suitable and effective administration of nucleoside analogues for the treatment of cancer patients. Here, we will review literature data concerning the recent development of novel purine nucleoside analogues (clofarabine, nelarabine and forodesine) and pyrimidine nucleoside analogues (troxacitabine, sapacitabine, CP-4055, 3-C-ethynylcytidine and 5-azapyrimidines) that are in evaluation at the clinical level.
Keywords: Antimetabolites, purine nucleosides, pyrimidine nucleosides, clofarabine, nelarabine, forodesine, troxacitabine, sapacitabine, 3'-C-ethynylcytidine, 5-azacytidine
Current Medicinal Chemistry
Title: Cytotoxic Nucleoside Analogues: Different Strategies to Improve their Clinical Efficacy
Volume: 15 Issue: 11
Author(s): C. M. Galmarini, F. Popowycz and B. Joseph
Affiliation:
Keywords: Antimetabolites, purine nucleosides, pyrimidine nucleosides, clofarabine, nelarabine, forodesine, troxacitabine, sapacitabine, 3'-C-ethynylcytidine, 5-azacytidine
Abstract: Cytotoxic nucleoside analogues are clinically important anticancer drugs. These agents behave as antimetabolites, compete with physiologic nucleosides, and, consequently, interact with a large number of intracellular targets to induce cytotoxicity. Nucleoside analogues share some general common characteristics, namely in terms of requiring transport by specific membrane transporters and intracellular metabolism. However these compounds differ in regard to the preferential interaction with certain targets which may explain why some compounds are more effective against rapidly proliferating tumours and others on neoplasia with a more protracted evolution. Purine and pyrimidine analogues are widely used not only as antileukaemic agents, but also as cytotoxic agents to treat solid tumours. However, the clinical use of these compounds is limited by important side-effects and primary or acquired drug resistance. Thus, there is an unmet medical need for the development of new antimetabolites and for technologies allowing a more suitable and effective administration of nucleoside analogues for the treatment of cancer patients. Here, we will review literature data concerning the recent development of novel purine nucleoside analogues (clofarabine, nelarabine and forodesine) and pyrimidine nucleoside analogues (troxacitabine, sapacitabine, CP-4055, 3-C-ethynylcytidine and 5-azapyrimidines) that are in evaluation at the clinical level.
Export Options
About this article
Cite this article as:
Galmarini M. C., Popowycz F. and Joseph B., Cytotoxic Nucleoside Analogues: Different Strategies to Improve their Clinical Efficacy, Current Medicinal Chemistry 2008; 15 (11) . https://dx.doi.org/10.2174/092986708784221449
DOI https://dx.doi.org/10.2174/092986708784221449 |
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
-
Effective Downregulation of BCR-ABL Tumorigenicity by RNA Targeted CRISPR-<i>Cas13a</i>
Current Gene Therapy Doxycycline in Mitochondrial Mediated Pathway of Apoptosis: A Systematic Review
Anti-Cancer Agents in Medicinal Chemistry Therapy of Elderly/Comorbid Patients with Chronic Lymphocytic Leukemia
Current Pharmaceutical Design Targeting Cancer Stem Cells with Natural Products
Current Drug Targets Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Serum Proteomics in the Diagnosis and Treatment of Haematological Malignancies
Current Proteomics Gene Delivery for Cancer Therapy
Current Drug Delivery Melatonin as a Pleiotropic Molecule with Therapeutic Potential for Type 2 Diabetes and Cancer
Current Medicinal Chemistry Anticancer Vitamin K3 Analogs: A Review
Anti-Cancer Agents in Medicinal Chemistry Structure and Ligand-based Design of P-glycoprotein Inhibitors: A Historical Perspective
Current Pharmaceutical Design Taking Risk Prediction to the Next Level. Advances in Biomarker Research for Atherosclerosis
Current Pharmaceutical Design Phosphoproteomics as a Promising Tool for Broadening the Analysis of Clinical Samples and for the Fight Against Cancer Disease
Current Pharmaceutical Analysis Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Genes Associated with Epithelial-Mesenchymal Transition: Possible Therapeutic Targets in Ductal Pancreatic Adenocarcinoma?
Anti-Cancer Agents in Medicinal Chemistry Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies
Current Cancer Drug Targets Targeting the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Network in Cancer Stem Cells
Current Medicinal Chemistry Hypocholesterolemia
Current Vascular Pharmacology Aminopeptidases of Malaria Parasites: New Targets for Chemotherapy
Infectious Disorders - Drug Targets Multifunctional Radiolabeled Nanoparticles for Targeted Therapy
Current Medicinal Chemistry Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?
Combinatorial Chemistry & High Throughput Screening