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
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
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
- 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
-
Transarterial Chemoembolization Followed by Hepatic Arterial Infusion
Chemotherapy Combined a Tyrosine Kinase Inhibitor for Treatment of
Large Hepatocellular Carcinoma
Current Cancer Drug Targets Atheromatosis Extent in Coronary Artery Disease is not Correlated with Apolipoprotein-E Polymorphism and its Plasma Levels, but Associated with Cognitive Decline
Current Alzheimer Research Role of Calcitonin Gene-Related Peptide in Gastric Mucosal Defence and Healing
Current Pharmaceutical Design Cardio-vascular Activity of Catestatin: Interlocking the Puzzle Pieces
Current Medicinal Chemistry Alkaloids as Vasodilator Agents: A Review
Current Pharmaceutical Design Human Placental Vascular Reactivity in Health and Disease: Implications for the Treatment of Pre-eclampsia
Current Pharmaceutical Design Heterozygosity in LDLR rs2228671 and rs72658855 Gene is Associated with Increased Risk of Developing Coronary Artery Disease in India –A Case-Control Study
Endocrine, Metabolic & Immune Disorders - Drug Targets Patents in Diagnosis of Preeclampsia
Recent Patents on Biomarkers Antihypertensive and ACE-2 Inhibitory Effects of <i>Daphne gnidium</i> in Rats
Cardiovascular & Hematological Agents in Medicinal Chemistry Update of Targeted Therapy-Induced Hypertension: Basics for Non-Oncology Providers
Current Hypertension Reviews The Unaddressed Issue of Optimal Antithrombotic Treatment after Coronary Artery Stenting in Patients with an Indication for Anticoagulation: Current Evidence and Suggested Practice
Vascular Disease Prevention (Discontinued) Prospective Medicines against the Widespread, Emergent, and Multidrugresistant Opportunistic Fungal Pathogen Candida auris: A Breath of Hope
Current Topics in Medicinal Chemistry Novel Molecular Targets in the Treatment of Cardiac Hypertrophy
Recent Patents on Cardiovascular Drug Discovery The APOE Genotype: Modification of Therapeutic Responses in Alzheimer's Disease
Current Pharmaceutical Design Relaxin, Insulin and Diabetes: An Intriguing Connection
Current Diabetes Reviews Human Platelets Express Authentic CB1 and CB2 Receptors
Current Neurovascular Research Evaluation and Management of Atrial Fibrillation
Cardiovascular & Hematological Disorders-Drug Targets Aldosteronism in Heart Failure: A Proinflammatory / Fibrogenic Cardiac Phenotype. Search for Biomarkers and Potential Drug Targets
Current Drug Targets Decrypting the Pathological Pathways in IgA Nephropathy
Recent Advances in Inflammation & Allergy Drug Discovery miRNA as an Ultimate and Emerging Diagnostic Approach for the Detection of Alzheimer’s Disease
MicroRNA