Abstract
Organic nitrates, such as nitroglycerin, have been used in clinical practice for more than one century for the treatment of angina, even before the identification of Nitric Oxide (NO) as the so-called Endothelium Derived Relaxing Factor (EDRF). Recently, multiple functions of this molecule in biology and pathophysiology have been discovered and alterations in the NO signalling pathway have often been associated with disease progression in mammals, providing a strong rationale for the use of NO as a potential drug. To have a therapeutic benefit from NO properties, an elegant approach has been designed coupling well-known existing drugs with moieties able to slowly release NO following enzymatic metabolism. "Hybrid nitrates", in which activities of both the native drug and NO are present, have been obtained with the aim of originating safer and more active drugs. The technology consists in the choice of the appropriate chemical spacer arm carrying the nitric ester in order to obtain the best pharmacodynamic and pharmacokinetic profile. The connecting linkers already explored are of different chemical structure, ranging from aliphatic chains to heteroaromatic rings. The molecules so far obtained have already demonstrated their potential therapeutic interest in both pharmacological tests and clinical trials. In this review, we describe the approach and the possibility of generating new chemical entities, combining well-known drugs with an NO-donating moiety in order to increase activity and safety, along with examples of their activity and potential therapeutic application in different pathologies. A few significant examples of molecules in the early preclinical stage, as well as in advanced clinical development will be described.
Keywords: nitric oxide, no-donors, hybrid nitrates, non steroidal anti-inflammatory drugs (nsaids), cox-inhibiting nitric oxide donators (cinods), steroids, antihypertensive drugs, naproxen, aspirin, gabapentin
Current Topics in Medicinal Chemistry
Title: Therapeutic Potential of Nitrate Esters of Commonly Used Drugs
Volume: 5 Issue: 7
Author(s): Manlio Bolla, Nicoletta Almirante and Francesca Benedini
Affiliation:
Keywords: nitric oxide, no-donors, hybrid nitrates, non steroidal anti-inflammatory drugs (nsaids), cox-inhibiting nitric oxide donators (cinods), steroids, antihypertensive drugs, naproxen, aspirin, gabapentin
Abstract: Organic nitrates, such as nitroglycerin, have been used in clinical practice for more than one century for the treatment of angina, even before the identification of Nitric Oxide (NO) as the so-called Endothelium Derived Relaxing Factor (EDRF). Recently, multiple functions of this molecule in biology and pathophysiology have been discovered and alterations in the NO signalling pathway have often been associated with disease progression in mammals, providing a strong rationale for the use of NO as a potential drug. To have a therapeutic benefit from NO properties, an elegant approach has been designed coupling well-known existing drugs with moieties able to slowly release NO following enzymatic metabolism. "Hybrid nitrates", in which activities of both the native drug and NO are present, have been obtained with the aim of originating safer and more active drugs. The technology consists in the choice of the appropriate chemical spacer arm carrying the nitric ester in order to obtain the best pharmacodynamic and pharmacokinetic profile. The connecting linkers already explored are of different chemical structure, ranging from aliphatic chains to heteroaromatic rings. The molecules so far obtained have already demonstrated their potential therapeutic interest in both pharmacological tests and clinical trials. In this review, we describe the approach and the possibility of generating new chemical entities, combining well-known drugs with an NO-donating moiety in order to increase activity and safety, along with examples of their activity and potential therapeutic application in different pathologies. A few significant examples of molecules in the early preclinical stage, as well as in advanced clinical development will be described.
Export Options
About this article
Cite this article as:
Bolla Manlio, Almirante Nicoletta and Benedini Francesca, Therapeutic Potential of Nitrate Esters of Commonly Used Drugs, Current Topics in Medicinal Chemistry 2005; 5 (7) . https://dx.doi.org/10.2174/1568026054679335
DOI https://dx.doi.org/10.2174/1568026054679335 |
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
-
Magnetic Field-Assisted Gene Delivery: Achievements and Therapeutic Potential
Current Gene Therapy Homocysteine and Non-Cardiac Vascular Disease
Current Pharmaceutical Design Hydrogen Sulfide: From Physiology to Pharmacology
Inflammation & Allergy - Drug Targets (Discontinued) Short-term High-Dose Effect of Lovastatin on Thrombolysis by rt-PA in a Human Whole-Blood in vitro Clot Model
Current Neurovascular Research Angelica Injection Reduces Cognitive Impairment during Chronic Cerebral Hypoperfusion through Brain-Derived Neurotrophic Factor and Nerve Growth Factor
Current Neurovascular Research Fatty Liver and Ischemia/Reperfusion: Are there Drugs Able to Mitigate Injury?
Current Medicinal Chemistry Peripheral Blood Derived Cell Trafficking for Cardiac Regeneration
Current Stem Cell Research & Therapy Integrin Signaling Networks in the Pathobiology of Vascular Smooth Muscle Cells
Vascular Disease Prevention (Discontinued) The Role of Colchicine in the Prevention of Cerebrovascular Ischemia
Current Pharmaceutical Design Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury
Current Stem Cell Research & Therapy Provoking Neuroprotection by Peroxynitrite
Current Pharmaceutical Design Strict Adherence to Guidelines in Decision Making for Coronary Angiography in Patients Who have Survived a Q Wave Myocardial Infarction; 2-Year Outcome in a Greek Population
Vascular Disease Prevention (Discontinued) Novel Anti-arrhythmic Medications in the Treatment of Atrial Fibrillation
Current Cardiology Reviews Mechanisms And Prevention Of TAVI-Related Cerebrovascular Events
Current Pharmaceutical Design Effects of Obesity on Vascular Potassium Channels
Current Vascular Pharmacology Repeated Restraint and Nerve Growth Factor Administration in Male and Female Mice: Effect on Sympathetic and Cardiovascular Mediators of the Stress Response
Current Neurovascular Research Fructose 1,6-Bisphosphate: A Summary of Its Cytoprotective Mechanism
Current Medicinal Chemistry Cerebral Aneurysm as an Exacerbating Factor in Stroke Pathology and a Therapeutic Target for Neuroprotection
Current Pharmaceutical Design Drugs of Abuse: Epigenetic Mechanisms in Toxicity and Addiction
Current Medicinal Chemistry Molecular Imaging to Monitor Repair of Myocardial Infarction Using Genetically Engineered Bone Marrow-Derived Mesenchymal Stem Cells
Current Gene Therapy