Abstract
In the present paper 25 known thermolysin inhibitors were docked into thermolysin using the Internal Coordinate Mechanics (ICM™) software. Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout™ program. The docking studies indicated that all 25 inhibitors coordinated the catalytic zinc in bidentate or monodentate geometry. A ‘three-point’ pharmacophore model was proposed which consisted of a hydrophobic group, a negative ionizable group and a hydrogen bond acceptor group. Finally the pharmacophore model has been tested against a small compound library containing 18 highly, moderately, less active as well as inactive compounds. The screening indicated that the pharmacophore model could, identify highly active compounds in front of inactive or less active ones.
Keywords: Thermolysin inhibitors, molecular docking, pharmacophore models, antibacterial drugs, antihypertensive drugs, thermolysin, Listeeria, Clostridium, Staphyloccus, Pseudomonas, Vibrio
Mini-Reviews in Medicinal Chemistry
Title:Binding Modes and Pharmacophore Modelling of Thermolysin Inhibitors
Volume: 12 Issue: 6
Author(s): M. T.H. Khan, Y. Wuxiuer and I. Sylte
Affiliation:
Keywords: Thermolysin inhibitors, molecular docking, pharmacophore models, antibacterial drugs, antihypertensive drugs, thermolysin, Listeeria, Clostridium, Staphyloccus, Pseudomonas, Vibrio
Abstract: In the present paper 25 known thermolysin inhibitors were docked into thermolysin using the Internal Coordinate Mechanics (ICM™) software. Pharmacophore models based on thermolysin binding modes and activity profiles were generated using the LigandScout™ program. The docking studies indicated that all 25 inhibitors coordinated the catalytic zinc in bidentate or monodentate geometry. A ‘three-point’ pharmacophore model was proposed which consisted of a hydrophobic group, a negative ionizable group and a hydrogen bond acceptor group. Finally the pharmacophore model has been tested against a small compound library containing 18 highly, moderately, less active as well as inactive compounds. The screening indicated that the pharmacophore model could, identify highly active compounds in front of inactive or less active ones.
Export Options
About this article
Cite this article as:
T.H. Khan M., Wuxiuer Y. and Sylte I., Binding Modes and Pharmacophore Modelling of Thermolysin Inhibitors, Mini-Reviews in Medicinal Chemistry 2012; 12 (6) . https://dx.doi.org/10.2174/138955712800493799
DOI https://dx.doi.org/10.2174/138955712800493799 |
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
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...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
- 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
-
Hypertension in the Elderly
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial: Can Glucagon Like Peptide 1 (GLP1) Agonists or Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors Ameliorate Non-Alcoholic Steatohepatitis in People with or without Diabetes?
Current Vascular Pharmacology The Obligatory Role of the Acetylcholine-Induced Endothelium-Dependent Contraction in Hypertension: Can Arachidonic Acid Resolve this Inflammation?
Current Pharmaceutical Design Tissue Distribution and Pharmacodynamics: A Complicated Relationship
Current Drug Metabolism Vascular Dementia: Atherosclerosis, Cognition and Alzheimers Disease
Current Alzheimer Research Editorial (Hot Topic: Introduction to the Special Issue: Relevance of Endocrine and Metabolic Disorders in Heart Failure: From Pathophysiology to Therapeutic Approach)
Endocrine, Metabolic & Immune Disorders - Drug Targets Delayed Neuroleptic Malignant Syndrome Associated with the Use of Low Dose Risperidone in Conjunction with Cholinergic Drugs-the Dangers of Polypharmacy in the Elderly
Current Drug Therapy Lifestyle Factors and Endothelial Function
Current Vascular Pharmacology Can Statins Prevent Progression of Degenerated Aortic Valve Stenosis?
Vascular Disease Prevention (Discontinued) A Link Between Hypertension and Atrial Fibrillation: Methods of Treatment and Prevention
Current Vascular Pharmacology Aldosterone Receptor Antagonists and Cardiovascular Disease: Do We Need a Change of the Guard?
Cardiovascular & Hematological Agents in Medicinal Chemistry Bevacizumab for Malignant Brain Gliomas. Which is the Current Evidence?
Recent Patents on Inflammation & Allergy Drug Discovery The Pleiotropic Effects of PPARs on Vascular Cells and Angiogenesis: Implications for Tissue Engineering
Current Stem Cell Research & Therapy Physiological Effect and Therapeutic Application of Alpha Lipoic Acid
Current Medicinal Chemistry Potential of Selected Indian Herbs for COVID-19
Current Traditional Medicine Nanocarriers Assisted siRNA Gene Therapy for the Management of Cardiovascular Disorders
Current Pharmaceutical Design Trace and Minor Element Concentrations in Aqueous Extract of the Herbal Medicinal Plants Tamarindus indica and Hibiscus sabdiffora
Current Nutrition & Food Science Resveratrol: A Therapeutic Approach to Neurodegenerative Diseases and Aging
Mini-Reviews in Organic Chemistry The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis
Current Medicinal Chemistry Non-Alcoholic Steatohepatitis: New Insights from OMICS Studies
Current Pharmaceutical Biotechnology