Abstract
The possibility to develop new antibacterial agents raised much interest recently. The main classes of antibiotics clinically used nowadays act towards the inhibition of four classical targets: a) cell wall biosynthesis; b) protein biosynthesis; c) DNA and RNA biosynthesis; d) folate biosynthesis. Recently, carbonic anhydrases (CAs, EC 4.2.1.1) started to be investigated in detail in pathogenic bacteria, in the search for antibiotics with a novel mechanism of action, since it has been demonstrated that in many bacteria, CAs are essential for the life cycle of the organism and that their inhibition leads to growth impairment or growth defects of the pathogen. CAs catalyze a simple but physiologically relevant reaction in all life kingdoms, carbon dioxide hydration to bicarbonate and protons. Several classes of CA inhibitors (CAIs) are known to date: the metal complexing anions and the unsubstituted sulfonamides, which bind to the Zn(II) ion of the enzyme either by substituting the non-protein zinc ligand or add to the metal coordination sphere, generating trigonal– bipyramidal species are the classical, most frequently investigated ones. In many cases effective inhibitors were detected, some of which also inhibited the bacterial growth in vivo. However, very few of the detected inhibitors were also selective for the bacterial over the human, off target isoforms such as hCA II. Using structure-based drug design processes, we estimate that it will be possible to achieve the desired selectivity for inhibiting preferentially the bacterial but not the host CA isoforms.
Keywords: Anions, antibacterial, antiinfective, carbonic anhydrase, CA inhibitors, hydratase activity, pathogens, selective inhibition, sulfonamide, X-ray.
Current Medicinal Chemistry
Title:An Overview of the Selectivity and Efficiency of the Bacterial Carbonic Anhydrase Inhibitors
Volume: 22 Issue: 18
Author(s): C. Capasso and C.T. Supuran
Affiliation:
Keywords: Anions, antibacterial, antiinfective, carbonic anhydrase, CA inhibitors, hydratase activity, pathogens, selective inhibition, sulfonamide, X-ray.
Abstract: The possibility to develop new antibacterial agents raised much interest recently. The main classes of antibiotics clinically used nowadays act towards the inhibition of four classical targets: a) cell wall biosynthesis; b) protein biosynthesis; c) DNA and RNA biosynthesis; d) folate biosynthesis. Recently, carbonic anhydrases (CAs, EC 4.2.1.1) started to be investigated in detail in pathogenic bacteria, in the search for antibiotics with a novel mechanism of action, since it has been demonstrated that in many bacteria, CAs are essential for the life cycle of the organism and that their inhibition leads to growth impairment or growth defects of the pathogen. CAs catalyze a simple but physiologically relevant reaction in all life kingdoms, carbon dioxide hydration to bicarbonate and protons. Several classes of CA inhibitors (CAIs) are known to date: the metal complexing anions and the unsubstituted sulfonamides, which bind to the Zn(II) ion of the enzyme either by substituting the non-protein zinc ligand or add to the metal coordination sphere, generating trigonal– bipyramidal species are the classical, most frequently investigated ones. In many cases effective inhibitors were detected, some of which also inhibited the bacterial growth in vivo. However, very few of the detected inhibitors were also selective for the bacterial over the human, off target isoforms such as hCA II. Using structure-based drug design processes, we estimate that it will be possible to achieve the desired selectivity for inhibiting preferentially the bacterial but not the host CA isoforms.
Export Options
About this article
Cite this article as:
Capasso C. and Supuran C.T., An Overview of the Selectivity and Efficiency of the Bacterial Carbonic Anhydrase Inhibitors, Current Medicinal Chemistry 2015; 22 (18) . https://dx.doi.org/10.2174/0929867321666141012174921
DOI https://dx.doi.org/10.2174/0929867321666141012174921 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) Recent Advances in Antiepileptic Herbal Medicine
Current Neuropharmacology Expression and Function of Cytochrome P450 in Brain Drug Metabolism
Current Drug Metabolism Pharmacological Characterization of Ligands at Recombinant NMDA Receptor Subtypes by Electrophysiological Recordings and Intracellular Calcium Measurements
Combinatorial Chemistry & High Throughput Screening Meet the Editorial Board Member
CNS & Neurological Disorders - Drug Targets Dysfunction of Mitochondrial ATP Production As a Target for Personalized Cancer Therapy
Current Pharmacogenomics and Personalized Medicine Pharmacological Inhibition of Voltage-gated Ca<sup>2+</sup> Channels for Chronic Pain Relief
Current Neuropharmacology Autism: Pathophysiology and Promising Herbal Remedies
Current Pharmaceutical Design Regulation of miRNA Processing and miRNA Mediated Gene Repression in Cancer
MicroRNA Recent Updates of Chemically Modified Electrodes in Pharmaceutical Analysis
Combinatorial Chemistry & High Throughput Screening Damaged Proteins Bearing L-Isoaspartyl Residues and Aging: A Dynamic Equilibrium Between Generation of Isomerized Forms and Repair by PIMT
Current Aging Science The Role of Structure Activity Relationship Studies in the Search for New GABA Uptake Inhibitors
Mini-Reviews in Medicinal Chemistry [General Articles] Cannabinoids: Mechanisms and Therapeutic Applications in the CNS
Current Medicinal Chemistry The Therapeutic Potential of Neural Stem Cells in Traumatic Brain Injuries
Current Signal Transduction Therapy Amyloid β Oligomers Decrease Hippocampal Spontaneous Network Activity in an Age-Dependent Manner
Current Alzheimer Research Synthesis and Anticonvulsant Activity of Some Novel 2-Methyl Imidazole Derivatives
Letters in Drug Design & Discovery A Comprehensive Review on Preclinical Evidence-based Neuroprotective Potential of <i>Bacopa monnieri</i> against Parkinson's Disease
Current Drug Targets High Temperature Unfolding Simulations of a Single-stranded DNA i-Motif
Current Physical Chemistry MicroRNAs as Biomarkers for Birth Defects
MicroRNA Effect of Hemodialysis on Pharmacokinetics of Ezogabine/Retigabine and its N-Acetyl Metabolite in Patients with End Stage Renal Disease
Current Clinical Pharmacology