Abstract
Nucleoside and nucleobase antimetabolites have substantially impacted treatment of cancer and infections. Their close resemblance to natural analogs gives them the power to interfere with a variety of intracellular targets, which on one hand gives them high potency, but on the other hand incurs severe side effects, especially of the chemotherapeutics used against malignancies. Therefore, the development of novel nucleoside analogs with widened therapeutic windows represents an attractive target to synthetic organic and medicinal chemists. This review discusses the current antimetabolite drugs: 5- fluorouracil, 6-mercaptopurine, 6-thioguanine, Cladribine, Vidaza, Decitabine, Emtricitabine, Abacavir, Sorivudine, Clofarabine, Fludarabine, and Nelarabine; gives insight into the nucleoside drug candidates that are being developed; and outlines the approaches to nucleobase modifications that may help discover novel bioactive nucleoside analogs with the mechanism of action focused on termination of DNA synthesis, which is expected to diminish the off-target toxicity in non-proliferating human cells.
Keywords: Antimetabolites, Anticancer and anti-microbial chemotherapeutics, Modified nucleobases, Nucleosides
Current Topics in Medicinal Chemistry
Title:Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future
Volume: 16 Issue: 11
Author(s): Matthew P. Burke, Kayla M. Borland and Vladislav A. Litosh
Affiliation:
Keywords: Antimetabolites, Anticancer and anti-microbial chemotherapeutics, Modified nucleobases, Nucleosides
Abstract: Nucleoside and nucleobase antimetabolites have substantially impacted treatment of cancer and infections. Their close resemblance to natural analogs gives them the power to interfere with a variety of intracellular targets, which on one hand gives them high potency, but on the other hand incurs severe side effects, especially of the chemotherapeutics used against malignancies. Therefore, the development of novel nucleoside analogs with widened therapeutic windows represents an attractive target to synthetic organic and medicinal chemists. This review discusses the current antimetabolite drugs: 5- fluorouracil, 6-mercaptopurine, 6-thioguanine, Cladribine, Vidaza, Decitabine, Emtricitabine, Abacavir, Sorivudine, Clofarabine, Fludarabine, and Nelarabine; gives insight into the nucleoside drug candidates that are being developed; and outlines the approaches to nucleobase modifications that may help discover novel bioactive nucleoside analogs with the mechanism of action focused on termination of DNA synthesis, which is expected to diminish the off-target toxicity in non-proliferating human cells.
Export Options
About this article
Cite this article as:
Burke P. Matthew, Borland M. Kayla and Litosh A. Vladislav, Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future, Current Topics in Medicinal Chemistry 2016; 16 (11) . https://dx.doi.org/10.2174/1568026615666150915111933
DOI https://dx.doi.org/10.2174/1568026615666150915111933 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Objective Biomarkers or Symptom Scores for the Classification of Fibromyalgia Syndrome?
Current Rheumatology Reviews The Neurobiological Bases for Development of Pharmacological Treatments of Aggressive Disorders
Current Neuropharmacology Role of Glucocorticoids in Breast Cancer
Current Pharmaceutical Design Synthesis of Medicinally Privileged Heterocycles through Dielectric Heating
Current Medicinal Chemistry Neoplastic Conditions in the Context of HIV-1 Infection
Current HIV Research Recognition of Nucleic Acids by Toll-Like Receptors and Development of Immunomodulatory Drugs
Current Medicinal Chemistry Advances in Hydrogels Applied to Degenerative Diseases
Current Pharmaceutical Design Abscopal Effect of Radiation Therapy and Signal Transduction
Current Signal Transduction Therapy Translational Peptide-associated Nanosystems: Promising Role as Cancer Vaccines
Current Topics in Medicinal Chemistry Theoretical Modeling of HPV: QSAR and Novodesign with Fragment Approach
Current Computer-Aided Drug Design Spermine Metabolism and Anticancer Therapy
Current Cancer Drug Targets Catechins as Model Bioactive Compounds for Biomedical Applications
Current Pharmaceutical Design Combination of Valproic Acid and ATRA Restores RARβ2 Expression and Induces Differentiation in Cervical Cancer through the PI3K/Akt Pathway
Current Molecular Medicine Tryptamine Induces Axonopathy and Mitochondriopathy Mimicking Neurodegenerative Diseases via Tryptophanyl-tRNA Deficiency
Current Alzheimer Research Development of Global Consensus of Dengue Virus Envelope Glycoprotein for Epitopes Based Vaccine Design
Current Computer-Aided Drug Design Synthesis and Biological Evaluation of 3-Substituted-4-(4-methylthio phenyl)-1HPyrrole Derivatives as Potential Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in T Cell Adoptive Immunotherapy of Cancer
Current Cancer Therapy Reviews Terpenes with Antitumor Activity: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery HIF-1 Inhibitors for Cancer Therapy: From Gene Expression to Drug Discovery
Current Pharmaceutical Design Botanical Therapeutics (Part II): Antimicrobial and In Vitro Anticancer Activity against MCF7 Human Breast Cancer Cells of Chamomile, Parsley and Celery Alcoholic Extracts
Anti-Cancer Agents in Medicinal Chemistry