Abstract
β2 agonists and anticholinergics are two major classes of bronchodilators which form first line of drugs recommended in symptomatic treatment of asthma and COPD. Combinational therapy involving β agonists and anticholinergics prove more effective in treating airway disease than use of either agent alone. In present investigation, binding modes of Muscarinic Antagonism and β 2 Agonism (MABA) conjugates designed by Lyn et al. were revealed on structural grounds adopting molecular docking techniques. The conjugates tether β 2 motif onto M3 motif which makes it a single molecule that acts as both β 2 agonist and antimuscarinic agent. Series of conjugates were docked against β 2 adrenergic receptor and modeled M3 muscarinic acetylcholine receptor and pharmacophoric features were identified. Upon screening the conjugates on the basis of receptor ligand free energy, hydrogen bonding and internal electrostatic interaction, conjugate 11 demonstrated superior interactions with the receptors compared to remaining conjugates in the series. While, in vitro results and in silico outcomes are in agreement to reveal that conjugate 11 to possess best pharmacological profile, binding modes obtained in docking can be utilized to design new conjugates with improved biological activity. A close study of receptor residues in binding site and atoms, groups and substructures of conjugates may be used to develop favourable secondary valence forces towards receptor-ligand interactions.
Keywords: Chronic obstructive pulmonary disease (COPD), asthma, bronchodilators, muscarinic antagonism and β 2 agonism (MABA) conjugates, comparative modeling, molecular docking, pharmacophore identification.
Current Topics in Medicinal Chemistry
Title:Binding Modes and Pharmacophoric Features of Muscarinic Antagonism and β2 Agonism (MABA) Conjugates
Volume: 13 Issue: 14
Author(s): Srinivas Bandaru, M. Hema Prasad, A. Jyothy, Anuraj Nayarisseri and Mukesh Yadav
Affiliation:
Keywords: Chronic obstructive pulmonary disease (COPD), asthma, bronchodilators, muscarinic antagonism and β 2 agonism (MABA) conjugates, comparative modeling, molecular docking, pharmacophore identification.
Abstract: β2 agonists and anticholinergics are two major classes of bronchodilators which form first line of drugs recommended in symptomatic treatment of asthma and COPD. Combinational therapy involving β agonists and anticholinergics prove more effective in treating airway disease than use of either agent alone. In present investigation, binding modes of Muscarinic Antagonism and β 2 Agonism (MABA) conjugates designed by Lyn et al. were revealed on structural grounds adopting molecular docking techniques. The conjugates tether β 2 motif onto M3 motif which makes it a single molecule that acts as both β 2 agonist and antimuscarinic agent. Series of conjugates were docked against β 2 adrenergic receptor and modeled M3 muscarinic acetylcholine receptor and pharmacophoric features were identified. Upon screening the conjugates on the basis of receptor ligand free energy, hydrogen bonding and internal electrostatic interaction, conjugate 11 demonstrated superior interactions with the receptors compared to remaining conjugates in the series. While, in vitro results and in silico outcomes are in agreement to reveal that conjugate 11 to possess best pharmacological profile, binding modes obtained in docking can be utilized to design new conjugates with improved biological activity. A close study of receptor residues in binding site and atoms, groups and substructures of conjugates may be used to develop favourable secondary valence forces towards receptor-ligand interactions.
Export Options
About this article
Cite this article as:
Bandaru Srinivas, Prasad Hema M., Jyothy A., Nayarisseri Anuraj and Yadav Mukesh, Binding Modes and Pharmacophoric Features of Muscarinic Antagonism and β2 Agonism (MABA) Conjugates, Current Topics in Medicinal Chemistry 2013; 13 (14) . https://dx.doi.org/10.2174/15680266113139990115
DOI https://dx.doi.org/10.2174/15680266113139990115 |
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
-
Oral Corticosteroid Use in Exacerbations of Asthma
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Beta-2 Agonists in Asthma: Medicine or Murderer?
Current Respiratory Medicine Reviews Liverworts-Potential Source of Medicinal Compounds
Current Pharmaceutical Design The Immunomodulatory Role of Vitamin D in Respiratory Diseases
Current Respiratory Medicine Reviews Prevention and Management of Hypertension Without Drugs
Current Hypertension Reviews Chirality - A New Era of Therapeutics
Mini-Reviews in Medicinal Chemistry The IL-12 Family of Cytokines in Infection, Inflammation and Autoimmune Disorders
Inflammation & Allergy - Drug Targets (Discontinued) Nuclear Targeting of Gold Nanoparticles for Improved Therapeutics
Current Topics in Medicinal Chemistry The Formulation of Lipid-Based Nanotechnologies for the Delivery of Fixed Dose Anticancer Drug Combinations
Current Drug Delivery Development of IL-5 Receptor Antagonists
Current Pharmaceutical Design Basophil Activation Test with Indomethacin to Assess Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs: A Preliminary Study
Inflammation & Allergy - Drug Targets (Discontinued) Potential Therapeutic Targeting of Platelet-Mediated Cellular Interactions in Atherosclerosis and Inflammation
Current Medicinal Chemistry IL-17A and Multiple Sclerosis: Signaling Pathways, Producing Cells and Target Cells in the Central Nervous System
Current Drug Targets New Oxazolidines Inhibit the Secretion of IFN-γ and IL-17 by PBMCS from Moderate to Severe Asthmatic Patients
Medicinal Chemistry Tachykinins and the Cardiovascular System
Current Drug Targets ANTI-ADHESION Evolves To a Promising Therapeutic Concept in Oncology
Current Medicinal Chemistry Colon Cancer and Specific Ways to Deliver Drugs to the Large Intestine
Anti-Cancer Agents in Medicinal Chemistry Electroconvulsive Therapy in Child and Adolescent Psychiatry
Current Psychiatry Reviews Biomarker-Detection Technologies for Comprehensive Medical Diagnosis During Deep-Space Missions
Recent Patents on Space Technology Relevance of the Deletion Polymorphisms of the Glutathione S-Transferases GSTT1 and GSTM1 in Pharmacology and Toxicology
Current Drug Metabolism