![conference banner](/images/conference-banner.jpeg)
Abstract
Serine proteases are attractive targets for the design of enzyme inhibitors since they are involved in the etiology of several diseases. Within the class of serine proteases, HLE is one of the most destructive enzymes in the body. It is implicated in the promotion or exacerbation of a number of diseases including pancreatitis, acute respiratory syndrome, rheumatoid arthritis, atherosclerosis, pulmonary emphysema, and cystic fibrosis. Thrombin, a trypsin-like serine protease, plays a dual role in thrombogenesis, including fibrin formation and platelet activation. As a result, thrombin constitutes one of the most widely studied targets for antithrombotic strategy. Numerous inhibitors of serine proteases have been reported during the past three decades. Among them, coumarin-type molecules displayed a high inhibitory potency towards various serine proteases. At that time, halomethyl dihydrocoumarins have been shown to behave as the first general suicide inhibitors of serine protease. These molecules inhibit several proteases such as human leucocyte elastase, porcine pancreatic elastase, thrombin, urokinase and human plasmin. Isocoumarins are very effective as mechanism-based inhibitors of serine proteases. Pharmacomodulation on the 3-alkoxy- 4-chloroisocoumarins and the 3-alkoxy-7-amino-4-chloroisocoumarins led to strong inhibitors of numerous serine proteases such as HLE, human factor XIa and XIIa, thrombin, urokinase and kallikrein. Recently, a series of coumarins characterised by an alkyl, aryl ester, amide, thioester or ketone in the position 3 and an electrophilic chloromethyl moiety in the position 6 have been developed. These compounds were found to be high inhibitors of α-chymotrypin, HLE and human thrombin.
Keywords: coumarins, enzyme inhibitors, serine protease inhibitors, isocoumarins
Current Pharmaceutical Design
Title: Coumarin and Isocoumarin as Serine Protease Inhibitors
Volume: 10 Issue: 30
Author(s): Lionel Pochet, Raphael Frederick and Bernard Masereel
Affiliation:
Keywords: coumarins, enzyme inhibitors, serine protease inhibitors, isocoumarins
Abstract: Serine proteases are attractive targets for the design of enzyme inhibitors since they are involved in the etiology of several diseases. Within the class of serine proteases, HLE is one of the most destructive enzymes in the body. It is implicated in the promotion or exacerbation of a number of diseases including pancreatitis, acute respiratory syndrome, rheumatoid arthritis, atherosclerosis, pulmonary emphysema, and cystic fibrosis. Thrombin, a trypsin-like serine protease, plays a dual role in thrombogenesis, including fibrin formation and platelet activation. As a result, thrombin constitutes one of the most widely studied targets for antithrombotic strategy. Numerous inhibitors of serine proteases have been reported during the past three decades. Among them, coumarin-type molecules displayed a high inhibitory potency towards various serine proteases. At that time, halomethyl dihydrocoumarins have been shown to behave as the first general suicide inhibitors of serine protease. These molecules inhibit several proteases such as human leucocyte elastase, porcine pancreatic elastase, thrombin, urokinase and human plasmin. Isocoumarins are very effective as mechanism-based inhibitors of serine proteases. Pharmacomodulation on the 3-alkoxy- 4-chloroisocoumarins and the 3-alkoxy-7-amino-4-chloroisocoumarins led to strong inhibitors of numerous serine proteases such as HLE, human factor XIa and XIIa, thrombin, urokinase and kallikrein. Recently, a series of coumarins characterised by an alkyl, aryl ester, amide, thioester or ketone in the position 3 and an electrophilic chloromethyl moiety in the position 6 have been developed. These compounds were found to be high inhibitors of α-chymotrypin, HLE and human thrombin.
Export Options
About this article
Cite this article as:
Pochet Lionel, Frederick Raphael and Masereel Bernard, Coumarin and Isocoumarin as Serine Protease Inhibitors, Current Pharmaceutical Design 2004; 10 (30) . https://dx.doi.org/10.2174/1381612043382684
DOI https://dx.doi.org/10.2174/1381612043382684 |
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
-
Carrier Mediated Systemic Delivery of Protein and Peptide Therapeutics
Current Pharmaceutical Design The Angiotensin Type 1 Receptor: A Drug Target to Reduce the Risk of Organ Transplant Rejection
Letters in Drug Design & Discovery Atorvastatin Sensitises Vascular Smooth Muscle Cells, but not Endothelial Cells, to TNF-α-induced Cell Death
Current Pharmaceutical Design Natural Flora and Anticancer Regime: Milestones and Roadmap
Anti-Cancer Agents in Medicinal Chemistry JAK2-mediated Intracellular Signaling
Current Molecular Medicine PET Tracers for Mapping Adenosine Receptors as Probes for Diagnosis of CNS Disorders
Central Nervous System Agents in Medicinal Chemistry Generation, Subsets and Functions of Inducible Regulatory T Cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Mixed Connective Tissue Disease: The Two Cases Representing the Range of this Illness
Current Rheumatology Reviews Computational Studies Applied to Anti-inflammatory Drug Discovery: A Review
Current Organic Chemistry Clinical Potential of Minocycline for Schizophrenia
CNS & Neurological Disorders - Drug Targets Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases
Current Organic Chemistry Naturally Occurring Methyl Salicylate Glycosides
Mini-Reviews in Medicinal Chemistry The ERK and p38MAPK Pathways as Targets for Anti-Inflammatory Therapy
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Modulation of Inducible Nitric Oxide Synthase Activation by Immuno-suppressive Drugs
Current Drug Metabolism A Glance Over the Cannabinoid Machinery to Design New Anti- Angiogenic Compounds
Mini-Reviews in Medicinal Chemistry The Potential Impact of Ayurvedic Traditional <i>Bhasma</i> on SARS-CoV- 2- Induced Pathogenesis
Current Traditional Medicine Nitrogen, Oxygen or Sulfur Containing Heterocyclic Compounds as Analgesic Drugs Used as Modulators of the Nitroxidative Stress
Mini-Reviews in Medicinal Chemistry Src Inhibitors and Angiogenesis
Current Pharmaceutical Design Targets to Tackle – The Pathophysiology of the Disease
Current Drug Targets Structure-Based Discovery of PDEs Inhibitors
Current Topics in Medicinal Chemistry