Abstract
Endothelin-1 (ET-1), a potent vasoconstrictor peptide, exerts its physiological effects by binding and activating specific G protein-coupled receptors, named ETA and ETB. An unique property of ET-1 is its ability to bind almost irreversibly to its receptors. Aspirin and salicylic acid (SA) are allosteric inhibitors of ET-1 binding to ETA receptors. Dihalogenated derivatives of SA have been identified as more potent allosteric inhibitors than aspirin. In this study, disubstituted benzohydroxamic acid, benzaldoximes and dihalosalicylic acid dimers were synthesized and tested as inhibitors of [125 I]ET-1 binding to ETA receptors in rat embryonic cardiomyocyte (H9c2 cell) membranes. Some dihalosalicylic acid dimers 2h showed good inhibitory activity, the most active compounds are the hydroxamic acids derived from anthranilic acid. Among these compounds, the 3, 5-diiodo-2-aminobenzohydroxamic acid e compound 2a is three-folds more potent as inhibitor of [125I] ET-1 binding to ETA receptors than the 3; 5-diiodosalicylic acid reported in literature. Most aryl aldoximes in this study were biologically inactive as inhibitors of [125I] ET-1 binding to ETA receptors.
Keywords: Allosteric, endothelin-1, hydroxamic acid, benzaldoxime, 3, 5-diiodo-2-aminobenzohydroxamic acid, 3, 5-diiodosalicylic acid, salicylic acid dimers, ETA receptors
Medicinal Chemistry
Title: Allosteric Inhibition of [125I] ET-1 Binding to ETA Receptors by Aldoxime and Hydroxamic Acid Derivatives
Volume: 4 Issue: 4
Author(s): Musa Ahmed, Susanna Nencetti, Maria R. Mazzoni, Francesca Porchia, Federica Antonelli and Annalina Lapucci
Affiliation:
Keywords: Allosteric, endothelin-1, hydroxamic acid, benzaldoxime, 3, 5-diiodo-2-aminobenzohydroxamic acid, 3, 5-diiodosalicylic acid, salicylic acid dimers, ETA receptors
Abstract: Endothelin-1 (ET-1), a potent vasoconstrictor peptide, exerts its physiological effects by binding and activating specific G protein-coupled receptors, named ETA and ETB. An unique property of ET-1 is its ability to bind almost irreversibly to its receptors. Aspirin and salicylic acid (SA) are allosteric inhibitors of ET-1 binding to ETA receptors. Dihalogenated derivatives of SA have been identified as more potent allosteric inhibitors than aspirin. In this study, disubstituted benzohydroxamic acid, benzaldoximes and dihalosalicylic acid dimers were synthesized and tested as inhibitors of [125 I]ET-1 binding to ETA receptors in rat embryonic cardiomyocyte (H9c2 cell) membranes. Some dihalosalicylic acid dimers 2h showed good inhibitory activity, the most active compounds are the hydroxamic acids derived from anthranilic acid. Among these compounds, the 3, 5-diiodo-2-aminobenzohydroxamic acid e compound 2a is three-folds more potent as inhibitor of [125I] ET-1 binding to ETA receptors than the 3; 5-diiodosalicylic acid reported in literature. Most aryl aldoximes in this study were biologically inactive as inhibitors of [125I] ET-1 binding to ETA receptors.
Export Options
About this article
Cite this article as:
Ahmed Musa, Nencetti Susanna, Mazzoni R. Maria, Porchia Francesca, Antonelli Federica and Lapucci Annalina, Allosteric Inhibition of [125I] ET-1 Binding to ETA Receptors by Aldoxime and Hydroxamic Acid Derivatives, Medicinal Chemistry 2008; 4 (4) . https://dx.doi.org/10.2174/157340608784872208
DOI https://dx.doi.org/10.2174/157340608784872208 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
- 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
-
Macrophage Colony-Stimulating Factor (M-CSF) in Plasma and CSF of Patients with Mild Cognitive Impairment and Alzheimers Disease
Current Alzheimer Research From Biomarkers to Cytokine-like Hormones: Uncovering New Directives for Cognitive Loss and Alzheimer’s Disease
Current Neurovascular Research Snake Venom Disintegrins: An Overview of their Interaction with Integrins
Current Drug Targets Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange
Current Neurovascular Research Recent Patents on Physical, Mineral & Organic Acid Composition of Golden Delicious and Red Delicious Apples (Malus×Domestica Borkh) Grown in the West of Iran
Recent Patents on Food, Nutrition & Agriculture PPARγ: Potential Therapeutic Target for Ailments Beyond Diabetes and its Natural Agonism
Current Drug Targets Beta-Blocker Therapy for Septic Cardiac Shock: Fiction Or Realism?
Current Drug Therapy Incidence and Management of Carfilzomib-induced Cardiovascular Toxicity; A Systematic Review and Meta-analysis
Cardiovascular & Hematological Disorders-Drug Targets A Critical Review of Bioactive Food Components, and of their Functional Mechanisms, Biological Effects and Health Outcomes
Current Pharmaceutical Design Rotational Atherectomy in Acute STEMI with Heavily Calcified Culprit Lesion is a Rule Breaking Solution
Current Cardiology Reviews Editorial (Thematic Issue: Multidisciplinary Imaging of the Coronary Circulation: A Fast Moving Field)
Recent Patents on Medical Imaging The Use of the Dahl Rat to Understand the Genetics of Human Hypertension: 35 Years of Data
Current Hypertension Reviews Pleiotropic Actions of PPARg Activators Thiazolidinediones in Cardiovascular Diseases
Current Pharmaceutical Design Application of Nanomedicine in Cardiovascular Diseases and Stroke
Current Pharmaceutical Design The Role of High-density Lipoprotein in Oral and Dental Diseases
Current Medicinal Chemistry Fragile X Mental Retardation Protein: Past, Present and Future
Current Protein & Peptide Science Optimized High-Yield Purification of Obesity-Associated Melanocortin 4 Receptor
Protein & Peptide Letters QbD-Oriented Development of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) of Valsartan with Improved Biopharmaceutical Performance
Current Drug Delivery Genetic Polymorphisms of Type-1 and Type-2 Inflammatory Cytokines in Ischaemic Stroke
Vascular Disease Prevention (Discontinued) New Thrombin and Factor Xa Inhibitors for Primary and Secondary Prevention of Ischaemic Stroke
CNS & Neurological Disorders - Drug Targets