Abstract
Cysteine proteases selectively catalyze the hydrolysis of peptide bonds. Uncontrolled, unregulated, or undesired proteolysis can lead to many disease states including emphysema, stroke, viral infections, cancer, Alzheimers disease, inflammation, and arthritis. Cysteine proteases inhibitors thus have considerable potential utility for therapeutic intervention in a variety of disease states. This review emphasizes on the new developments from literature reports on Michael acceptors as potential cysteine protease inhibitors, namely vinyl sulfones, α,β-unsaturated carbonyl derivatives and aza-peptides. These compounds irreversibly alkylate the active site cysteine residue via conjugate addition. Examples of Michael acceptors inhibitors that have already progressed to clinical testing are also presented.
Keywords: Cysteine protease inhibitors, vinyl sulfone, α,β-unsaturated carbonyl derivative, aza-peptide Michael acceptor, K-777, Ruprintivir
Mini-Reviews in Medicinal Chemistry
Title: Michael Acceptors as Cysteine Protease Inhibitors
Volume: 7 Issue: 10
Author(s): Maria M.M. Santos and Rui Moreira
Affiliation:
Keywords: Cysteine protease inhibitors, vinyl sulfone, α,β-unsaturated carbonyl derivative, aza-peptide Michael acceptor, K-777, Ruprintivir
Abstract: Cysteine proteases selectively catalyze the hydrolysis of peptide bonds. Uncontrolled, unregulated, or undesired proteolysis can lead to many disease states including emphysema, stroke, viral infections, cancer, Alzheimers disease, inflammation, and arthritis. Cysteine proteases inhibitors thus have considerable potential utility for therapeutic intervention in a variety of disease states. This review emphasizes on the new developments from literature reports on Michael acceptors as potential cysteine protease inhibitors, namely vinyl sulfones, α,β-unsaturated carbonyl derivatives and aza-peptides. These compounds irreversibly alkylate the active site cysteine residue via conjugate addition. Examples of Michael acceptors inhibitors that have already progressed to clinical testing are also presented.
Export Options
About this article
Cite this article as:
Santos M.M. Maria and Moreira Rui, Michael Acceptors as Cysteine Protease Inhibitors, Mini-Reviews in Medicinal Chemistry 2007; 7 (10) . https://dx.doi.org/10.2174/138955707782110105
DOI https://dx.doi.org/10.2174/138955707782110105 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
Related Articles
-
Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias
Current Cardiology Reviews Electrochemical Cell-based Biosensors for Biomedical Applications
Current Topics in Medicinal Chemistry Why Does Obesity Increase the Risk for Cardiovascular Disease?
Current Pharmaceutical Design Re-Balancing of Inflammation and Aβ Immunity as a Therapeutic for Alzheimers Disease-View from the Bedside
CNS & Neurological Disorders - Drug Targets Tachykinins and the Cardiovascular System
Current Drug Targets 2015 Update of Erectile Dysfunction Management Following Radical Prostatectomy: From Basic Research to Clinical Management
Current Pharmaceutical Design Effects of High-Fat Diets from Different Sources on Serum and Thymus Lipid Profile: Study in an Experimental Model
Endocrine, Metabolic & Immune Disorders - Drug Targets Transporters at CNS Barrier Sites: Obstacles or Opportunities for Drug Delivery?
Current Pharmaceutical Design Potential Role of Natural Compounds Against Skin Aging
Current Medicinal Chemistry Locus (Coeruleus) Minoris Resistentiae in Pathogenesis of Alzheimer’s Disease
Current Alzheimer Research Prevention of Upper Gastrointestinal Ulcer and Complications in Low-Dose Aspirin Users
Current Pharmaceutical Design Gastrophysics of the Oral Cavity
Current Pharmaceutical Design Using Extracellular Matrix-Derived Peptides to Alter the Microenvironment for Myocardial Repair
Current Vascular Pharmacology Biomarkers Insights in Psoriasis - Regulatory Cytokines
Current Biomarkers (Discontinued) Two Cases of Glucose-6-phosphate Dehydrogenase Deficiency Presenting as Symptomatic Methemoglobinemia with Persistently Low Saturations After Fava Bean Ingestion in United Arab Emirates
Applied Clinical Research, Clinical Trials and Regulatory Affairs Biological Consequences of Dysfunctional HDL
Current Medicinal Chemistry Design, Characterization and Clinical Evaluation of Curcumin Dental Film for the Treatment of Periodontitis
Drug Delivery Letters Rewiring the Heart: Stem Cell Therapy to Restore Normal Cardiac Excitability and Conduction
Current Stem Cell Research & Therapy Patent Selections:
Recent Patents on Cardiovascular Drug Discovery Biological Characterization and Preliminary Crystallization: A Step Towards the Use of Novel Allium sativum Protease Inhibitor as a Potential Therapeutic Drug
Current Enzyme Inhibition