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
-
Molecular Recognition Mechanisms for Detecting Cell Death In Vivo
Current Pharmaceutical Biotechnology Bioactivities of Iridoids
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Left Ventricular 2-[<sup>18</sup>F]-Fluoro-2-Deoxy-D-Glucose Uptake Using Modified Oral Glucose Loading Protocol With Pre-Medicated Niacin On Positron Emission Tomography/Computed Tomography - A Preliminary Study
Current Molecular Imaging (Discontinued) Sodium Ion Transporters as New Therapeutic Targets in Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry Trigger, Signaling Mechanism and End Effector of Cardioprotective Effect of Remote Postconditioning of Heart
Current Cardiology Reviews Dynamics of Toll-like Receptors Signaling in Skeletal Muscle Atrophy
Current Medicinal Chemistry Essential Roles of Toll-Like Receptors in Atherosclerosis
Current Medicinal Chemistry Susceptibility of Periodontopathogenic and Cariogenic Bacteria to Defensins and Potential Therapeutic Use of Defensins in Oral Diseases
Current Pharmaceutical Design Chest Pain in Children
Current Pediatric Reviews Human Adipose-Derived Stem Cells Delay Retinal Degeneration in Royal College of Surgeons Rats Through Anti-Apoptotic and VEGF-Mediated Neuroprotective Effects
Current Molecular Medicine Efficient Expression and Purification of Recombinant Therapeutic Protein Candidates, Human Midkine and Pleiotrophin
Current Pharmaceutical Biotechnology Animal Models of Diabetes Mellitus: Relevance to Vascular Complications
Current Pharmaceutical Design Application of Stem Cells in Cardiology: Where we are and where we are Going
Current Stem Cell Research & Therapy Tanshinone IIA: Pharmacology, Total Synthesis, and Progress in Structure-modifications
Current Medicinal Chemistry NLRP3 Is Involved in Ischemia/Reperfusion Injury
CNS & Neurological Disorders - Drug Targets Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment
Current Pharmaceutical Design Multimodality Imaging of RNA Interference
Current Medicinal Chemistry Echocardiogram versus Cardiac Magnetic Resonance Imaging for the Diagnosis of Non-compaction Cardiomyopathy – A Case Report
New Emirates Medical Journal Editorial (Thematic Issue: Novel Insights into the Role of Anesthetics and Opioids in Organ or Tissue Protection)
Current Pharmaceutical Design Normal Ventricular Functional Reference Parameters on Magnetic Resonance Imaging in Healthy Children
Current Medical Imaging