Abstract
The widely clinically used benzothiadiazines and high ceiling diuretics, such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide, contain SO2NH2 moieties acting as an effective zincbinding function in carbonic anhydrases (CAs, EC 4.2.1.1) inhibitors. These drugs were launched in a period when only isoform CA II was known and considered physiologically/pharmacologically relevant. Although acting as moderate-weak inhibitors of CA II, all these drugs considerably inhibit other CA isozymes known nowadays to be involved in critical physiologic processes, among the 16 CAs present in vertebrates. Some low nanomolar (or even subnanomolar) inhibitors against such isoforms were recently detected, such as metholazone against CA VII, XII and XIII, chlorthalidone against CA VB, VII, IX, XII and XIII, indapamide against CA VII, IX, XII and XIII, furosemide against CA I, II and XIV, and bumethanide against CA IX and XII. The X-ray crystal structure of the CA II – indapamide adduct was also reported recently, revealing interesting aspects useful for the drug design of CA inhibitors. It has also been proposed that the recently observed beneficial effect of indapamide for the treatment of patients with hypertension and type 2 diabetes might be due to its potent inhibition of CA isoforms present in kidneys and blood vessels, which would thus explain both the blood pressure lowering effects as well as organ-protective activity of the drug. Thus, these old drugs may be useful as leads for new applications.
Current Pharmaceutical Design
Title: Diuretics: From Classical Carbonic Anhydrase Inhibitors to Novel Applications of the Sulfonamides
Volume: 14 Issue: 7
Author(s): Claudiu T. Supuran
Affiliation:
Abstract: The widely clinically used benzothiadiazines and high ceiling diuretics, such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide, contain SO2NH2 moieties acting as an effective zincbinding function in carbonic anhydrases (CAs, EC 4.2.1.1) inhibitors. These drugs were launched in a period when only isoform CA II was known and considered physiologically/pharmacologically relevant. Although acting as moderate-weak inhibitors of CA II, all these drugs considerably inhibit other CA isozymes known nowadays to be involved in critical physiologic processes, among the 16 CAs present in vertebrates. Some low nanomolar (or even subnanomolar) inhibitors against such isoforms were recently detected, such as metholazone against CA VII, XII and XIII, chlorthalidone against CA VB, VII, IX, XII and XIII, indapamide against CA VII, IX, XII and XIII, furosemide against CA I, II and XIV, and bumethanide against CA IX and XII. The X-ray crystal structure of the CA II – indapamide adduct was also reported recently, revealing interesting aspects useful for the drug design of CA inhibitors. It has also been proposed that the recently observed beneficial effect of indapamide for the treatment of patients with hypertension and type 2 diabetes might be due to its potent inhibition of CA isoforms present in kidneys and blood vessels, which would thus explain both the blood pressure lowering effects as well as organ-protective activity of the drug. Thus, these old drugs may be useful as leads for new applications.
Export Options
About this article
Cite this article as:
Supuran T. Claudiu, Diuretics: From Classical Carbonic Anhydrase Inhibitors to Novel Applications of the Sulfonamides, Current Pharmaceutical Design 2008; 14 (7) . https://dx.doi.org/10.2174/138161208783877947
DOI https://dx.doi.org/10.2174/138161208783877947 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
The Impact of Diabetes on Mortality Among Elderly Patients Admitted for Treatment at a Hospital for Cardiovascular Disease in Southern Brazil
Current Diabetes Reviews A Multidisciplinary Atrial Fibrillation Clinic
Current Cardiology Reviews Some Peculiar Effects of NO-Synthase Inhibition on the Structure and Function of Cardiovascular System
Current Pharmaceutical Biotechnology Cocaine Dependence and Stroke: Pathogenesis and Management
Current Neurovascular Research Platelets in Rheumatic Diseases: Friend or Foe?
Current Pharmaceutical Design Regulation of Blood Flow by Prostaglandins
Current Vascular Pharmacology An Impact of Lifestyle Modification on Insulin Resistance in Hypertensive Patients with Metabolic Syndrome
Current Hypertension Reviews Recent Advances on Nitric Oxide in the Upper Airways
Current Medicinal Chemistry Depression in Coronary Heart Disease Patients: Etiological and Screening Issues
Current Psychiatry Reviews Facing Up the ROS Labyrinth - Where To Go?
Current Vascular Pharmacology Metal Oxide Nanoparticles: Potential Uses in Biomedical Applications
Current Proteomics Nitric Oxide and Dietary Factors: Part IV Traditional Japanese Food (Soy Products, Fish and Tea)
Vascular Disease Prevention (Discontinued) Glutathione Modulation and Oxidative Stress in Human Liver Slices
Current Drug Discovery Technologies The Effects of Interleukin-10 on the Expression of Fas and FasL in Rat Hepatic Stellate Cells
Medicinal Chemistry Interest of α2-Adrenergic Agonists and Antagonists in Clinical Practice: Background, Facts and Perspectives
Current Topics in Medicinal Chemistry The Profile of Angiogenic Factors in Vitreous Humor of the Patients with Proliferative Diabetic Retinopathy
Current Molecular Medicine Longitudinal Association between White Matter Hyperintensities and White Matter Beta-Amyloid Deposition in Cognitively Unimpaired Elderly
Current Alzheimer Research Neuroimmune Aspects of Sjogren`s Syndrome: Role of VIP/VPAC System in Immune and Salivary Gland Epithelial Cell Function
Current Pharmaceutical Design TRP Channels: Emerging Links Between Ca2+, Kidney and Hypertension
Current Hypertension Reviews Before and After Preeclampsia: What Biomarkers are there?
Current Women`s Health Reviews