![conference banner](/images/conference-banner.jpeg)
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
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Adynamic Ileus Induced by Varenicline
Current Drug Safety Sildenafil and Cardioprotection
Current Pharmaceutical Design The Development of Topically Acting Carbonic Anhydrase Inhibitors as Antiglaucoma Agents
Current Topics in Medicinal Chemistry Advanced Glycation End Products (AGEs) and Cardiovascular Disease (CVD) in Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry Repetitive Transcranial Magnetic Stimulation to Treat Substance Use Disorders and Compulsive Behavior
CNS & Neurological Disorders - Drug Targets “Legal Highs” – New Players in the Old Drama
Current Drug Abuse Reviews Nano-constructed Carriers Loaded With Antioxidant: Boon For Cardiovascular System
Current Pharmaceutical Design Enzyme Inhibition in Managing Cardiovascular Diseases
Current Enzyme Inhibition Editorial
Recent Patents on CNS Drug Discovery (Discontinued) Advancement in Beneficial Effects of AVE 0991: A Brief Review
Mini-Reviews in Medicinal Chemistry Metabolic Effects of a Diet with Inulin-Enriched Pasta in Healthy Young Volunteers
Current Pharmaceutical Design Ocular Toxocariasis: New Diagnostic and Therapeutic Perspectives
Recent Patents on Anti-Infective Drug Discovery Subject Index to Volume 1
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Synthesis and Biological Evaluation of Curcumin-Nitroxide-Based Molecular Hybrids as Antioxidant and Anti-Proliferative Agents
Medicinal Chemistry Proteasome Modulator 9 and Depression in Type 2 Diabetes
Current Medicinal Chemistry Clinical Pharmacology of Novel Anti-Alzheimer Disease Modifying Medications
Current Topics in Medicinal Chemistry Calcium Modification Therapies in Contemporary Percutaneous Coronary Intervention
Current Cardiology Reviews Targeting Fibrosis in Systemic Sclerosis
Endocrine, Metabolic & Immune Disorders - Drug Targets New Trends in Thromboxane and Prostacyclin Modulators
Current Medicinal Chemistry Gonadal Hormones in Adolescent Females with β-Thalassemia in Relation to Iron Load
Endocrine, Metabolic & Immune Disorders - Drug Targets