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
-
Green Synthesis of Silver Nanoparticle using Sechium edule Aqueous Extract and Study of Antimicrobial and Catalytic Activity
Current Nanomaterials The Role of Stromal Components in Pancreatic Cancer Progression
Anti-Cancer Agents in Medicinal Chemistry Nutrients Mediate Bioavailability and Turnover of Proteins in Mammals
Current Protein & Peptide Science Immunomodulation in Inflammatory Neuropathies: Rationale and Safety
Current Drug Safety Multifunctional Radiolabeled Nanoparticles for Targeted Therapy
Current Medicinal Chemistry Evidence of 68Ga-DOTA-NT-20.3 Uptake in Pancreatic Adenocarcinoma AsPC-1 Cell Line – in vitro Study
Current Pharmaceutical Biotechnology Role of Alterations in the Apoptotic Machinery in Sensitivity of Cancer Cells to Treatment
Current Pharmaceutical Design Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening
Current Cancer Drug Targets Prostate Cancer Gene Expression Marker 1 (PCGEM1): A Patented Prostate- Specific Non-Coding Gene and Regulator of Prostate Cancer Progression
Recent Patents on DNA & Gene Sequences Antiandrogens in Prostate Cancer Endocrine Therapy
Current Cancer Drug Targets Editorial (Thematic Issue: In vivo MRS: Techniques and Applications)
Current Molecular Imaging (Discontinued) Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Towards an Experimental and Systems Biology Framework for Cancer Cell Therapeutics
Current Bioinformatics Understanding and Targeting Osteoclastic Activity in Prostate Cancer Bone Metastases
Current Molecular Medicine Antecedents of Voluntary Surgical Sterilization Among Poor Women in Tamil Nadu: Urban vs. Rural Areas
Current Women`s Health Reviews Potential Therapeutic Agents from the Red Sea Organisms
Medicinal Chemistry Novel Agents in the Management of Lung Cancer
Current Medicinal Chemistry Screening for Silent Coronary Artery Disease in Diabetics- or Not?
Current Diabetes Reviews Antisense and/or Immunostimulatory Oligonucleotide Therapeutics
Current Cancer Drug Targets Imaging of HER-2 Overexpression in Tumors for Guiding Therapy
Current Pharmaceutical Design