Abstract
Cyclooxygenase is a key enzyme responsible for metabolisation of arachidonic acid into prostaglandins and thromboxane. This enzyme is the target of non steroidal anti-inflammatory drugs (NSAIDs), used against inflammation and pain. The inducible COX-2 was associated with inflammatory conditions, whereas the constitutive form (COX-1) was responsible for the beneficial effects of the PGs. This observation led to the development of COX-2 inhibitors or “coxibs” of which rofecoxib (Vioxx®) characterized by a methylsulfone moiety and the sulfonamides celecoxib (Celebrex®) and valdecoxib (Bextra®). Initially described as COX-2 “selective” inhibitors, recent reports revealed a nanomolar inhibition activity of the sulfonamide COX-2 inhibitors for several carbonic anhydrase (CA) isoforms, confirmed by X-ray crystal structures for the adducts of celecoxib and valdecoxib with isozyme CA II. This dual activity may help to explain differences in clinical observation between sulfonamide and methylsulfone COX-2 inhibitors. Moreover, the inhibition of CA isozymes, critical for the development and invasion of cancer cells, such as CA II, IX and XII, may constitute an important mechanism of antitumor action of such sulfonamide compounds.
Keywords: COX-2 expression, COX isoforms, thromboxane, CA9 promoter, prostaglandins
Current Topics in Medicinal Chemistry
Title: Dual Carbonic Anhydrase - Cyclooxygenase-2 Inhibitors
Volume: 7 Issue: 9
Author(s): Jean-Michel Dogne, Anne Thiry, Domenico Pratico, Bernard Masereel and Claudiu T. Supuran
Affiliation:
Keywords: COX-2 expression, COX isoforms, thromboxane, CA9 promoter, prostaglandins
Abstract: Cyclooxygenase is a key enzyme responsible for metabolisation of arachidonic acid into prostaglandins and thromboxane. This enzyme is the target of non steroidal anti-inflammatory drugs (NSAIDs), used against inflammation and pain. The inducible COX-2 was associated with inflammatory conditions, whereas the constitutive form (COX-1) was responsible for the beneficial effects of the PGs. This observation led to the development of COX-2 inhibitors or “coxibs” of which rofecoxib (Vioxx®) characterized by a methylsulfone moiety and the sulfonamides celecoxib (Celebrex®) and valdecoxib (Bextra®). Initially described as COX-2 “selective” inhibitors, recent reports revealed a nanomolar inhibition activity of the sulfonamide COX-2 inhibitors for several carbonic anhydrase (CA) isoforms, confirmed by X-ray crystal structures for the adducts of celecoxib and valdecoxib with isozyme CA II. This dual activity may help to explain differences in clinical observation between sulfonamide and methylsulfone COX-2 inhibitors. Moreover, the inhibition of CA isozymes, critical for the development and invasion of cancer cells, such as CA II, IX and XII, may constitute an important mechanism of antitumor action of such sulfonamide compounds.
Export Options
About this article
Cite this article as:
Dogne Jean-Michel, Thiry Anne, Pratico Domenico, Masereel Bernard and Supuran T. Claudiu, Dual Carbonic Anhydrase - Cyclooxygenase-2 Inhibitors, Current Topics in Medicinal Chemistry 2007; 7 (9) . https://dx.doi.org/10.2174/156802607780636717
DOI https://dx.doi.org/10.2174/156802607780636717 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Multiscale Modelling of Relationships between Protein Classes and Drug Behavior Across all Diseases Using the CANDO Platform
Mini-Reviews in Medicinal Chemistry Carbohydrate-Metal Complexes and their Potential as Anticancer Agents
Current Medicinal Chemistry Role of Hsp70 in Cancer Growth and Survival
Protein & Peptide Letters Cancer Chemoprevention Drug Targets
Current Drug Targets Targeted Therapies in Combination with Radiotherapy in Oesophageal and Gastroesophageal Carcinoma
Current Medicinal Chemistry Cardiovascular and Metabolic Effects of Ghrelin
Current Diabetes Reviews Mini-Review: Nucleus-Targeted Ribonucleases As Antitumor Drugs
Current Medicinal Chemistry Role of Epithelial Mesenchymal Transition in Prostate Tumorigenesis
Current Pharmaceutical Design Progress in Immunotherapy of Head and Neck Squamous Cell Carcinoma
Current Molecular Pharmacology Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review
Anti-Cancer Agents in Medicinal Chemistry Non Polymeric Nanoparticles for Photodynamic Therapy Applications: Recent Developments
Current Medicinal Chemistry Recent Advances in Medicinal Applications of Coinage-Metal (Cu and Ag) N-Heterocyclic Carbene Complexes
Current Topics in Medicinal Chemistry Anticancer Potential of Thiazole Derivatives: A Retrospective Review
Mini-Reviews in Medicinal Chemistry Therapeutical Relevance of MAP-Kinase Inhibitors in Renal Diseases: Current Knowledge and Future Clinical Perspectives
Current Medicinal Chemistry Association of ATG7 Polymorphisms and Clear Cell Renal Cell Carcinoma Risk
Current Molecular Medicine Sugar Based Biopolymers in Nanomedicine; New Emerging Era for Cancer Imaging and Therapy
Current Topics in Medicinal Chemistry MicroRNA Pathways: An Emerging Role in Identification of Therapeutic Strategies
Current Gene Therapy Heat Shock Protein 90 Inhibitors as Broad Spectrum Anti-Infectives
Current Pharmaceutical Design From Proteins to Nucleic Acid-Based Drugs: The Role of Biotech in Anti-VEGF Therapy
Anti-Cancer Agents in Medicinal Chemistry