Abstract
Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor’s metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.
Keywords: α-Amylase inhibitor; GRIP docking; Antidiabetic agents; Acarbose; Pseudotetrasaccharide.
Current Topics in Medicinal Chemistry
Title:Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose
Volume: 16 Issue: 23
Author(s): Rajeev Kumar Singla, Radha Singh and Ashok Kumar Dubey
Affiliation:
Keywords: α-Amylase inhibitor; GRIP docking; Antidiabetic agents; Acarbose; Pseudotetrasaccharide.
Abstract: Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor’s metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.
Export Options
About this article
Cite this article as:
Singla Kumar Rajeev, Singh Radha and Dubey Kumar Ashok, Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose, Current Topics in Medicinal Chemistry 2016; 16 (23) . https://dx.doi.org/10.2174/1568026616666160414123500
DOI https://dx.doi.org/10.2174/1568026616666160414123500 |
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
-
Human Use of Leucoselect® Phytosome® with Special Reference to Inflammatory- Allergic Pathologies in Frail Elderly Patients
Current Pharmaceutical Design Overview of Green Tea Interaction with Cardiovascular Drugs
Current Pharmaceutical Design The Vitamin D Neuroendocrine System as a Target for Novel Neurotropic Drugs
CNS & Neurological Disorders - Drug Targets The Neuropathology of Vascular Disease in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS)
Current Alzheimer Research The Updated Role of the Blood Brain Barrier in Subarachnoid Hemorrhage: From Basic and Clinical Studies
Current Neuropharmacology The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases
Current Molecular Pharmacology Meet Our Editorial Board Member:
Current Drug Safety Autonomic Dysfunction and Depression: A Biomarker of MDD Across the Life Span
Current Psychiatry Reviews Management of Osteoporosis: Seeing the Future
Medicinal Chemistry Reviews - Online (Discontinued) The Potential Role of Thiamine (Vitamin B1) in Diabetic Complications
Current Diabetes Reviews Seasonal and Perennial Allergic Conjunctivitis
Recent Patents on Inflammation & Allergy Drug Discovery Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions
Current Vascular Pharmacology Gender Differences in Response to Therapy for Cardiovascular Diseases
Current Pharmacogenomics and Personalized Medicine Acute Renal Failure in Different Malignant Tumors
Current Medicinal Chemistry Mechanisms of Neuronal Damage and Neuroprotection Underlying Ischemia/Reperfusion Injury after Physical Exercise
Current Drug Targets Bleomycin and its Role in Inducing Apoptosis and Senescence in Lung Cells - Modulating Effects of Caveolin-1
Current Cancer Drug Targets Acute Severe Colitis: Infliximab and/or Cyclosporine?
Current Drug Targets The Role of Dietary Fats in Hypertension, Obesity and Insulin Resistance: A Comparative Study of Animals and Humans in Fetal and Adult Life
Current Nutrition & Food Science Neonatal Ultrasound in Transport
Current Pediatric Reviews Management of Blood Pressure and Heart Rate in Patients with Acute Stroke
Current Pharmaceutical Design