![conference banner](/images/conference-banner.jpeg)
Abstract
α-Glucosidase (EC 3.2.1.20) enzyme belongs to the glycosidase family enzymes, cleave the glycosidic bond of the oligosaccharides that liberate glucose and its inhibition retards the carbohydrate digestion. In the present review, we have discussed the structural features of different α-glucosidase inhibitors (small molecules) responsible for the inhibitory activities. The reported computational studies including, QSAR, pharmacophore modelling, homology models, docking (with analogs enzymes), etc revealed that the topological, electronic and hydrophobicity properties determine the interactions of those molecules. The aromatic substituents connected with flexible bonds in the molecules have significant effect on the interactions, which may due to the presence of aromatic amino acid residues in the active site. The reported homology modelled and other analogs enzymes (enzymes of other species) also confirmed the existence of aromatic residue (amino acids) especially, histidine, phenylalanine and tyrosine in their active site along with the polar (glutamic and aspartic acids) residues. Multiple sequence alignments of the α-glucosidase enzymes (from different species) described that the abovementioned amino acid residues are present in the active site of all the studied enzymes. Recently, Celgosivir (MIGENIX Inc) is an oral prodrug of the natural product castanospermine used for the treatment of HCV infection by inhibiting α-glucosidase I. BMN-701 is an α-glucosidase inhibitors in the phase I pipeline (BioMarine) for the treatment of Pompe diseases. CKD-711 and CKD-711a are aminooligosaccharide α-glucosidase inhibitors and the in vitro study of CKD-711 showed similar effects to acarbose on porcine intestinal maltase and sucrase (IC50s of 2.5 and 0.5 μg/ml). This review also concluded that many α-glucosidases inhibitors obtained from natural products are used for the treatment of various carbohydrate mediated diseases. The structural analysis of these synthetic and natural derivatives guide for the development of novel semisynthetic/synthetic α-glucosidase inhibitors with free of toxicities.
Keywords: α-Glucosidases, HIV, QSAR, hydrophobicity, vdW surface area.
Mini-Reviews in Medicinal Chemistry
Title:Studies on α-Glucosidase Inhibitors Development: Magic Molecules for the Treatment of Carbohydrate Mediated Diseases
Volume: 12 Issue: 8
Author(s): N. S.H.N. Moorthy, M. J. Ramos and P. A. Fernandes
Affiliation:
Keywords: α-Glucosidases, HIV, QSAR, hydrophobicity, vdW surface area.
Abstract: α-Glucosidase (EC 3.2.1.20) enzyme belongs to the glycosidase family enzymes, cleave the glycosidic bond of the oligosaccharides that liberate glucose and its inhibition retards the carbohydrate digestion. In the present review, we have discussed the structural features of different α-glucosidase inhibitors (small molecules) responsible for the inhibitory activities. The reported computational studies including, QSAR, pharmacophore modelling, homology models, docking (with analogs enzymes), etc revealed that the topological, electronic and hydrophobicity properties determine the interactions of those molecules. The aromatic substituents connected with flexible bonds in the molecules have significant effect on the interactions, which may due to the presence of aromatic amino acid residues in the active site. The reported homology modelled and other analogs enzymes (enzymes of other species) also confirmed the existence of aromatic residue (amino acids) especially, histidine, phenylalanine and tyrosine in their active site along with the polar (glutamic and aspartic acids) residues. Multiple sequence alignments of the α-glucosidase enzymes (from different species) described that the abovementioned amino acid residues are present in the active site of all the studied enzymes. Recently, Celgosivir (MIGENIX Inc) is an oral prodrug of the natural product castanospermine used for the treatment of HCV infection by inhibiting α-glucosidase I. BMN-701 is an α-glucosidase inhibitors in the phase I pipeline (BioMarine) for the treatment of Pompe diseases. CKD-711 and CKD-711a are aminooligosaccharide α-glucosidase inhibitors and the in vitro study of CKD-711 showed similar effects to acarbose on porcine intestinal maltase and sucrase (IC50s of 2.5 and 0.5 μg/ml). This review also concluded that many α-glucosidases inhibitors obtained from natural products are used for the treatment of various carbohydrate mediated diseases. The structural analysis of these synthetic and natural derivatives guide for the development of novel semisynthetic/synthetic α-glucosidase inhibitors with free of toxicities.
Export Options
About this article
Cite this article as:
S.H.N. Moorthy N., J. Ramos M. and A. Fernandes P., Studies on α-Glucosidase Inhibitors Development: Magic Molecules for the Treatment of Carbohydrate Mediated Diseases, Mini-Reviews in Medicinal Chemistry 2012; 12 (8) . https://dx.doi.org/10.2174/138955712801264837
DOI https://dx.doi.org/10.2174/138955712801264837 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Drugs and mitochondria
Mitochondria play a central role in the life and death of cells. They are not merely the center for energy metabolism but are also the headquarters for different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Mitochondria maintain homeostasis in the cell by interacting with reactive oxygen-nitrogen species ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer’s, Parkinson’s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
![Wayfinder Image](/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
Related Articles
-
Safety and Efficacy of Aliskiren in the Treatment of Hypertension and Associated Clinical Conditions
Current Drug Safety LncRNA as a Therapeutic Target for Angiogenesis
Current Topics in Medicinal Chemistry The Impact of Inflammatory Profile on Selenium Levels in Hemodialysis Patients
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Pleiotropic Effects of HDL: Towards New Therapeutic Areas for HDL-Targeted Interventions
Current Molecular Medicine Research Trend of Persian Medicine Based on the PubMed Database, 2015 -2019
Current Traditional Medicine Platelet Turnover in Atherothrombotic Disease
Current Pharmaceutical Design The Heme Oxygenase/Biliverdin Reductase Pathway in Drug Research and Development
Current Drug Metabolism The Utility of Oral Diabetes Medications in Type 2 Diabetes of the Young
Current Diabetes Reviews Periostin Acts as a Bridge between Gestational Diabetes Mellitus (GDM) and Chronic Inflammation to Modulate Insulin Resistance by Modulating PPARα/NF-κB/TNF-α Signaling Pathway
Endocrine, Metabolic & Immune Disorders - Drug Targets Acute Coronary Syndrome and its Antithrombotic Treatment: Focus on Aspirin and Clopidogrel Resistance
Current Vascular Pharmacology Toll-Like Receptors and Human Disease: Lessons from Single Nucleotide Polymorphisms
Current Genomics Gestational Diabetes and the Metabolic Syndrome: Can Obesity and Small, Dense Low Density Lipoproteins be Key Mediators of this Association?
Current Pharmaceutical Biotechnology Peroxisome Proliferator-Activated Receptor (PPAR)β /δ: A New Potential Therapeutic Target for the Treatment of Metabolic Syndrome
Current Molecular Pharmacology HMGB-1 as a Target for Inflammation Controlling
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Pharmacotherapy of Schizophrenia: The Past, Present and Future
Current Drug Therapy Managing Sleep Disturbance in Bipolar Disorder
Current Psychiatry Reviews The Etiology of Hypertension in the Metabolic Syndrome Part Two: The Gene-Environment Interaction
Current Vascular Pharmacology The Role of Renin Angiotensin System Blockade in the Treatment of Atrial Fibrillation
Current Drug Targets - Cardiovascular & Hematological Disorders Challenges in Vascular Repair by Endothelial Progenitor Cells in Diabetic Patients
Cardiovascular & Hematological Disorders-Drug Targets Biomarkers Associated with Stroke Risk in Atrial Fibrillation
Current Medicinal Chemistry