Abstract
Glycosylation as one of most important post-translational modification of gene products is often critical to specific cellular biological functions. Since elevated glycoprocessing enzyme activities have been implicated in the development of various diseases including cancer metastasis, glycosidases and glycosyltransferases are considered as therapeutic targets. Azasugars, the first generation of enzyme inhibitors, have been extensively investigated and two azasugar-based drugs (Miglitol and Miglustat) have been approved. Aza-C-glycosides, molecules with an azasugar core and various C-aglycons attached at the pseudo anomeric center, have the potential to become the second-generation inhibitors with improved specificity and membrane permeability. In this review, C-glycosides, aza-C-glycosides, and aza- C-disaccharides are introduced as glycoprocessing enzyme inhibitors. The synthetic approaches toward those molecules are described based on the key reactions, which include reductive amination, nucleophilic ring opening of epoxides, nucleophilic addition to imines (C=N), and hetero-Michael additions. Aza-C-glycoside-based libraries are also described for the discovery of promising second-generation inhibitors.
Keywords: C-glycoside, aza-C-glycoside, glycosidase, glycosyltransferase, inhibitor
Current Topics in Medicinal Chemistry
Title: C-Glycosides and Aza-C-Glycosides as Potential Glycosidase and Glycosyltransferase Inhibitors
Volume: 5 Issue: 14
Author(s): Wei Zou
Affiliation:
Keywords: C-glycoside, aza-C-glycoside, glycosidase, glycosyltransferase, inhibitor
Abstract: Glycosylation as one of most important post-translational modification of gene products is often critical to specific cellular biological functions. Since elevated glycoprocessing enzyme activities have been implicated in the development of various diseases including cancer metastasis, glycosidases and glycosyltransferases are considered as therapeutic targets. Azasugars, the first generation of enzyme inhibitors, have been extensively investigated and two azasugar-based drugs (Miglitol and Miglustat) have been approved. Aza-C-glycosides, molecules with an azasugar core and various C-aglycons attached at the pseudo anomeric center, have the potential to become the second-generation inhibitors with improved specificity and membrane permeability. In this review, C-glycosides, aza-C-glycosides, and aza- C-disaccharides are introduced as glycoprocessing enzyme inhibitors. The synthetic approaches toward those molecules are described based on the key reactions, which include reductive amination, nucleophilic ring opening of epoxides, nucleophilic addition to imines (C=N), and hetero-Michael additions. Aza-C-glycoside-based libraries are also described for the discovery of promising second-generation inhibitors.
Export Options
About this article
Cite this article as:
Zou Wei, C-Glycosides and Aza-C-Glycosides as Potential Glycosidase and Glycosyltransferase Inhibitors, Current Topics in Medicinal Chemistry 2005; 5 (14) . https://dx.doi.org/10.2174/156802605774642999
DOI https://dx.doi.org/10.2174/156802605774642999 |
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
-
Proteasome Inhibitors in Cancer Therapy
Current Drug Targets The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery
Current Cancer Drug Targets Sunlight Vitamin D and Skin Cancer
Anti-Cancer Agents in Medicinal Chemistry NEDD4: A Promising Target for Cancer Therapy
Current Cancer Drug Targets Patent Selections
Recent Patents on Biotechnology Production of β -cyclodextrin from pH and Thermo Stable Cyclodextrin Glycosyl Transferase, Obtained from Arthrobacter mysorens and Its Evaluation as a Drug Carrier for Irbesartan
Current Drug Delivery In Vivo Optical Imaging in Gene & Cell Therapy
Current Gene Therapy Trichostatin A - like Hydroxamate Histone Deacetylase Inhibitors as Therapeutic Agents: Toxicological Point of View
Current Medicinal Chemistry miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma
Current Genomics Targeting Blood Vessels for the Treatment of Non-Small Cell Lung Cancer
Current Cancer Drug Targets Drug-Resistance in Central Nervous System Tumors: From the Traditional Cell-Resistance Model to the Genetically Driven Approaches on Therapy
Current Pharmaceutical Biotechnology Recovery of Locomotor Function with Combinatory Drug Treatments Designed to Synergistically Activate Specific Neuronal Networks
Current Medicinal Chemistry PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development
Current Drug Targets Topoisomerases and Tubulin Inhibitors: A Promising Combination for Cancer Treatment
Current Medicinal Chemistry - Anti-Cancer Agents Pharmacogenomics of Non-Small Cell Lung Cancer
Current Pharmacogenomics Hypoxia Inducible Factor-1 as a Target for Neurodegenerative Diseases
Current Medicinal Chemistry The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance
Current Drug Targets Role of Cannabinoids and Endocannabinoids in Cerebral Ischemia
Current Pharmaceutical Design Targeting Angiogenesis in Head and Neck Cancer
Current Cancer Drug Targets