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
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
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...read more
![](/images/wayfinder.jpg)
- 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
-
Cdc20: A Potential Novel Therapeutic Target for Cancer Treatment
Current Pharmaceutical Design Toll-Like Receptors: Cost or Benefit for Cancer?
Current Pharmaceutical Design Comparative Proteomics of Liver of the Diabetic Obese db/db and Non-Obese or Diabetic Mice
Current Proteomics Microarray Analysis of Human Epithelial Cell Responses to Bacterial Interaction
Infectious Disorders - Drug Targets The Forward Path for Biopharmaceuticals and Biosimilars: Emerging Options in the Selection of Host Cell Systems
Current Biotechnology Pharmacophore Modeling and 3D QSAR Studies of Novel Human Carbonic Anhydrase IX Inhibitors
Letters in Drug Design & Discovery Methionine Aminopeptidases as Potential Targets for Treatment of Gastrointestinal Cancers and other Tumors
Current Drug Targets Electromagnetic Energy as a Bridge Between Atomic and Cellular Levels in the Genetics Approach to Cancer Treatment
Current Topics in Medicinal Chemistry Immune Response Manipulation: Recombinant Immunoreceptors Endow T-Cells with Predefined Specificity
Current Pharmaceutical Design Circulating Tumor Cells: A Reliable Biomarker for Prostate Cancer Treatment Assessment?
Current Drug Metabolism Chemoradiotherapy of Human Tumors: Novel Approaches from Nanomedicine
Current Pharmaceutical Design Design and Endpoints of Clinical and Translational Trials in Advanced Colorectal Cancer. A Proposal from GROUP Español Multidisciplinar en Cancer Digestivo (GEMCAD)
Reviews on Recent Clinical Trials Evaluation of the Effects of 1,25 Vitamin D3 on Regulatory T Cells and T Helper 17 Cells in Vitamin D-deficient Women with Unexplained Recurrent Pregnancy Loss
Current Molecular Pharmacology Evaluation of Anticancer, Antibacterial and Antioxidant Properties of a Medicinally Treasured Fern Tectaria coadunata with its Phytoconstituents Analysis by HR-LCMS
Anti-Cancer Agents in Medicinal Chemistry Immune Responses to Adenovirus and Adeno-Associated Vectors Used for Gene Therapy of Brain Diseases: The Role of Immunological Synapses in Understanding the Cell Biology of Neuroimmune Interactions
Current Gene Therapy Induction of Autophagic Cell Death in Apoptosis-resistant Pancreatic Cancer Cells using Benzo[α]phenoxazines Derivatives, 10-methyl-benzo[α]phenoxazine-5-one and benzo[α]phenoxazine-5-one
Anti-Cancer Agents in Medicinal Chemistry Safe and Effective Kinase Inhibitors for the Treatment of Gynecological Cancers: In Silico Approach
Current Drug Metabolism Intracellular Fate of Peptide-Mediated Delivered Cargoes
Current Pharmaceutical Design ABC Transporters: Unvalidated Therapeutic Targets in Cancer and the CNS
Anti-Cancer Agents in Medicinal Chemistry Non-Genotoxic p53-Activators and their Significance as Antitumor Therapy of Future
Current Medicinal Chemistry