Abstract
Glutamine synthetase (E.C. 6.3.1.2) – an enzyme catalyzing formation of glutamine from glutamate and ammonium ion, is one of the most important enzymes in nitrogen metabolism. Due to glutamine synthetase activity, inorganic nitrogen is incorporated in the cell metabolism and is further used in biosynthesis of several highly important metabolites. The first part of the review presents the long-dating research on inhibitors of glutamine synthetase which started with the discovery of methionine sulfoximine in 1949. Since that time several inhibitors of this enzyme, classified in the following groups: derivatives of methionine sulfoximine, phosphorus containing analogues of glutamic acid, bisphosphonates and miscellaneous inhibitors, have been developed and described. Analysis of their structure-activity relationships is presented in some detail. The second part of the paper is dedicated to potential medical application of glutamine synthetase inhibitors, which proved to act as effective anti-tuberculosis agents with high selectivity towards the pathogenic bacteria. Moreover, it was also shown that glutamine synthetase inhibitors could be successfully applied in cancer therapy.
Keywords: Glutamine Synthetase, Inhibitors, enzyme catalyzing formation, cell metabolism, structure-activity relationships, medicinal application
Mini-Reviews in Medicinal Chemistry
Title: Inhibitors of Glutamine Synthetase and their Potential Application in Medicine
Volume: 8 Issue: 9
Author(s): Lukasz Berlicki
Affiliation:
Keywords: Glutamine Synthetase, Inhibitors, enzyme catalyzing formation, cell metabolism, structure-activity relationships, medicinal application
Abstract: Glutamine synthetase (E.C. 6.3.1.2) – an enzyme catalyzing formation of glutamine from glutamate and ammonium ion, is one of the most important enzymes in nitrogen metabolism. Due to glutamine synthetase activity, inorganic nitrogen is incorporated in the cell metabolism and is further used in biosynthesis of several highly important metabolites. The first part of the review presents the long-dating research on inhibitors of glutamine synthetase which started with the discovery of methionine sulfoximine in 1949. Since that time several inhibitors of this enzyme, classified in the following groups: derivatives of methionine sulfoximine, phosphorus containing analogues of glutamic acid, bisphosphonates and miscellaneous inhibitors, have been developed and described. Analysis of their structure-activity relationships is presented in some detail. The second part of the paper is dedicated to potential medical application of glutamine synthetase inhibitors, which proved to act as effective anti-tuberculosis agents with high selectivity towards the pathogenic bacteria. Moreover, it was also shown that glutamine synthetase inhibitors could be successfully applied in cancer therapy.
Export Options
About this article
Cite this article as:
Berlicki Lukasz, Inhibitors of Glutamine Synthetase and their Potential Application in Medicine, Mini-Reviews in Medicinal Chemistry 2008; 8 (9) . https://dx.doi.org/10.2174/138955708785132800
DOI https://dx.doi.org/10.2174/138955708785132800 |
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
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
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
Posaconazole: A New Antifungal Weapon
Reviews on Recent Clinical Trials The Mast Cell Pathway to Inflammation and Homeostasis: Pharmacolo- gical Insights
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Oncogene-Directed Therapies as Modulators of Cancer Coagulopathy, Angiogenesis and Tumor-Vascular Interface
Current Signal Transduction Therapy Design, Synthesis and In Vitro Evaluation of 18β-Glycyrrhetinic Acid Derivatives for Anticancer Activity Against Human Breast Cancer Cell Line MCF-7
Current Medicinal Chemistry Radioprotective Effects of Amifostine, L-Carnitine and Vitamin E in Preventing Early Salivary Gland Injury due to Radioactive Iodine Treatment
Current Medical Imaging Potential Future of New Glutamate Agonists and Antagonists Development
Anti-Cancer Agents in Medicinal Chemistry Aldose Reductase Inhibitors and Nanodelivery of Diabetic Therapeutics
Mini-Reviews in Medicinal Chemistry Single Emulsion-Solvent Evaporation Technique and Modifications for the Preparation of Pharmaceutical Polymeric Nanoparticles
Recent Patents on Drug Delivery & Formulation The Ubiquitin-Proteasome System as a Prospective Molecular Target for Cancer Treatment and Prevention
Current Protein & Peptide Science Antimicrobial Potential of Benzamides and Derived Nanosystems for Controlling in vitro Biofilm Development on Medical Devices
Current Organic Chemistry Benzothiazoles: How Relevant in Cancer Drug Design Strategy?
Anti-Cancer Agents in Medicinal Chemistry Brain Cancer: Implication to Disease, Therapeutic Strategies and Tumor Targeted Drug Delivery Approaches
Recent Patents on Anti-Cancer Drug Discovery Role of Protein Tyrosine Phosphatases in Plants
Current Genomics Daclatasvir: The First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A
Current Medicinal Chemistry Recent Patents on Heat Shock Proteins Targeting Antibodies
Recent Patents on Anti-Cancer Drug Discovery Cell Cycle as a Target of Antineoplastic Drugs
Current Pharmaceutical Design CETUXIMAB: From Bench to Bedside
Current Cancer Drug Targets Bruton Kinase Inhibitors in Chronic Lymphocytic Leukemia
Anti-Cancer Agents in Medicinal Chemistry Tribulus arabicus and Tribulus macropterus are Comparable to Tribulus terrestris: An Antioxidant Assessment
Current Bioactive Compounds Photodynamic Therapy For Non-Melanoma Skin Cancers
Current Cancer Therapy Reviews