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
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
-
Targeted Elimination of Leukemia Stem Cells; a New Therapeutic Approach in Hemato-Oncology
Current Drug Targets Current Perspective of Natural Alkaloid Carbazole and its Derivatives as Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases - Part II
Current Medicinal Chemistry Liver Stem Cells and Possible Clinical Applications
Current Stem Cell Research & Therapy CD20-based Immunotherapy of B-cell Derived Hematologic Malignancies
Current Cancer Drug Targets Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment
Current Cardiology Reviews Antibody Engineering, Virus Retargeting and Cellular Immunotherapy: One Ring to Rule Them All?
Current Gene Therapy Gene Delivery for Cancer Therapy
Current Drug Delivery Comparison of Uptake Mechanisms for Anthracyclines in Human Leukemic Cells
Current Drug Delivery Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment
Current Drug Targets Gene Therapy Strategies Towards Immune Tolerance to Treat the Autoimmune Diseases
Current Gene Therapy Alternatives to Conventional Vaccines - Mediators of Innate Immunity
Current Drug Targets Quassinoids from Brucea Javanica Seeds Inhibiting the Replication of Tobacco Mosaic Virus
Current Bioactive Compounds Improving Cancer Therapeutics by Molecular Profiling
Current Drug Metabolism Natural Products Chemistry in Marine Ascidians of the Genus Aplidium
Mini-Reviews in Organic Chemistry Tyrosine Kinase Blockers: New Hope for Successful Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Immunotherapy Resistance Mechanisms in Renal Cell Cancer
Current Signal Transduction Therapy Recent Advances in the Therapeutic Perspectives of Nutlin-3
Current Pharmaceutical Design α-Methylene-γ-lactones as a Novel Class of Anti-leukemic Agents
Anti-Cancer Agents in Medicinal Chemistry MicroRNAs as Cancer Biomarkers
MicroRNA