Abstract
α-Glucosidase inhibitors are marketed as therapeutic drugs for diabetes that act through the inhibition of carbohydrate metabolism. Inhibitors of the α-glucosidases that are involved in the biosynthesis of N-linked oligosaccharide chains have been reported to have antitumor, antiviral, and apoptosis-inducing activities, and some have been used clinically. α-Glucosidase inhibitors have interesting biological activities, and their design, synthesis, and screening are being actively performed. In quite a few reports, however, α-glucosidases with different origins than the target α-glucosidases, have been used to evaluate inhibitory activities. There might be confusion regarding the naming of α-glucosidases. For example, the term α-glucosidase is sometimes used as a generic name for α-glucoside hydrolases. Moreover, IUBMB recommends the use of “α-glucosidase” (EC 3.2.1.20) for exo-α-1,4-glucosidases, which are further classified into four families based on amino acid sequence similarities. Accordingly, substrate specificity and susceptibility to inhibitors varies markedly among enzymes in the IUBMB α-glucosidases. The design and screening of inhibitors without consideration of these differences is not efficient. For the development of a practical inhibitor that is operational in cells, HTS using the target α-glucosidase and the computer-aided design of inhibitors based on enzymatic information concerning the same α-glucosidase are essential.
Keywords: α-glucosidase, substrate specificity, inhibitor, HTS, virtual screening, in silico, structure based drug design
Current Topics in Medicinal Chemistry
Title: Design and Screening Strategies for α-Glucosidase Inhibitors Based on Enzymological Information
Volume: 9 Issue: 1
Author(s): Wataru Hakamata, Masaaki Kurihara, Haruhiro Okuda, Toshiyuki Nishio and Tadatake Oku
Affiliation:
Keywords: α-glucosidase, substrate specificity, inhibitor, HTS, virtual screening, in silico, structure based drug design
Abstract: α-Glucosidase inhibitors are marketed as therapeutic drugs for diabetes that act through the inhibition of carbohydrate metabolism. Inhibitors of the α-glucosidases that are involved in the biosynthesis of N-linked oligosaccharide chains have been reported to have antitumor, antiviral, and apoptosis-inducing activities, and some have been used clinically. α-Glucosidase inhibitors have interesting biological activities, and their design, synthesis, and screening are being actively performed. In quite a few reports, however, α-glucosidases with different origins than the target α-glucosidases, have been used to evaluate inhibitory activities. There might be confusion regarding the naming of α-glucosidases. For example, the term α-glucosidase is sometimes used as a generic name for α-glucoside hydrolases. Moreover, IUBMB recommends the use of “α-glucosidase” (EC 3.2.1.20) for exo-α-1,4-glucosidases, which are further classified into four families based on amino acid sequence similarities. Accordingly, substrate specificity and susceptibility to inhibitors varies markedly among enzymes in the IUBMB α-glucosidases. The design and screening of inhibitors without consideration of these differences is not efficient. For the development of a practical inhibitor that is operational in cells, HTS using the target α-glucosidase and the computer-aided design of inhibitors based on enzymatic information concerning the same α-glucosidase are essential.
Export Options
About this article
Cite this article as:
Hakamata Wataru, Kurihara Masaaki, Okuda Haruhiro, Nishio Toshiyuki and Oku Tadatake, Design and Screening Strategies for α-Glucosidase Inhibitors Based on Enzymological Information, Current Topics in Medicinal Chemistry 2009; 9 (1) . https://dx.doi.org/10.2174/156802609787354306
DOI https://dx.doi.org/10.2174/156802609787354306 |
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
-
Vascular Disrupting Agents (VDAs) in Anticancer Therapy
Current Clinical Pharmacology Analysis of the Potential for HIV-1 Vpr as an Anti-Cancer Agent
Current HIV Research Targeting Metabolic Enzymes in Cancer – Clinical Trials Update
Current Enzyme Inhibition The Relevance of Microdialysis for Clinical Oncology
Current Clinical Pharmacology Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer
Current Medicinal Chemistry Phospholipase D Inhibition: Beneficial and Harmful Consequences for a Double-Dealer Enzyme
Current Enzyme Inhibition Effects of Iron Chelation in Osteosarcoma
Current Cancer Drug Targets Beclin 1 Biology and its Role in Heart Disease
Current Cardiology Reviews Prospective Plant Based Anticancer Lead Molecules
Current Topics in Medicinal Chemistry Inhibitory Effects of Substituted Cinnamic Acid Esters on Mushroom Tyrosinase
Letters in Drug Design & Discovery Computational Evaluation and In Vitro Validation of New Epidermal Growth Factor Receptor Inhibitors
Current Topics in Medicinal Chemistry Chalcones in Cancer: Understanding their Role in Terms of QSAR. II Part
Mini-Reviews in Medicinal Chemistry Putative Mechanisms of Viral Transmission and Molecular Dysregulation of Mammary Epithelial Cells by Human Papillomavirus: Implications for Breast Cancer
Current Molecular Medicine Matrix Metalloproteinases
Current Medicinal Chemistry Anti-VEGF Mediated Immunomodulatory Role of Phytochemicals: Scientific Exposition for Plausible HCC Treatment
Current Drug Targets Exploring AT2R and its Polymorphism in Different Diseases: An Approach to Develop AT2R as a Drug Target beyond Hypertension
Current Drug Targets Radiotracers in Oncology
Current Radiopharmaceuticals Recent Developments in Patents Targeting Toll-Like Receptor Genes
Recent Patents on DNA & Gene Sequences Targeting Angiogenesis for Treatment of NSCLC Brain Metastases
Current Cancer Drug Targets DNA Repair Pathways and Human Metastatic Malignant Melanoma
Current Molecular Medicine