Abstract
We describe the details of the magnetic resonance spectroscopy and chemical shift imaging techniques for the human brain which have been developed over the last two decades. With these non-invasive tools, it is now readily possible to repeatedly assay up to 20 common brain metabolites. From the perspective of drug discovery, each of these metabolites could fulfill a number of useful functions: disease biomarker, surrogate marker of drug delivery, surrogate marker of drug efficacy and so on. To facilitate the possible utility of clinical magnetic resonance spectroscopy in future drug discovery, the major portion of the review is devoted to a detailed description of the well-validated neurochemical profiles of many common human brain disorders, for which MRS data now exists. Beyond proton, MRS, the commonest tool provided by the manufacturers of clinical MRI equipment, lays the world of heteronuclear NMR more familiar to chemists. Here too, with relatively little effort it has been possible to define neurochemical profiles of human brain disorders using 13C MRS. The future for drug discovery scientists is discussed. Finally, recognizing that a known feature of MR is the lack of sensitivity, we describe new efforts to harness hyperpolarization, with its 50,000 signal amplification, to conventional MRS.
Keywords: Spectroscopy, metabolites, biomarkers, drug discovery, MR spectroscopy, MRS, molecular imaging, Positron Emission Tomography, PET, neurospectroscopy, ISIS, PRESS, STEAM, CSI, nuclear Overhauser effect, NOE, N-Acetylaspartate, NAA, Creatine, Phosphocreatine, Myo-Inositol, Scyllo-Inositol, astrocytes, pseudodementia, Hepatic encephalopathy, transient ischemic attack (TIA), MELAS, mitochondrial encephalopathy with lactic acidosis, Neonatal hypoxia, Closed Head Trauma, Closed head injury, traumatic brain injury, Toxoplasmosis, CNS lymphoma, progressive multifocal leukoencephalopathy, Cryptococcoma, cytochrome P4502D6, CYP2D6, P-glycoprotein efflux transport, receptor imaging indicators
Current Topics in Medicinal Chemistry
Title: Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery
Volume: 11 Issue: 1
Author(s): Brian Ross, Thao Tran, Pratip Bhattacharya, D. Martin Watterson and Napapon Sailasuta
Affiliation:
Keywords: Spectroscopy, metabolites, biomarkers, drug discovery, MR spectroscopy, MRS, molecular imaging, Positron Emission Tomography, PET, neurospectroscopy, ISIS, PRESS, STEAM, CSI, nuclear Overhauser effect, NOE, N-Acetylaspartate, NAA, Creatine, Phosphocreatine, Myo-Inositol, Scyllo-Inositol, astrocytes, pseudodementia, Hepatic encephalopathy, transient ischemic attack (TIA), MELAS, mitochondrial encephalopathy with lactic acidosis, Neonatal hypoxia, Closed Head Trauma, Closed head injury, traumatic brain injury, Toxoplasmosis, CNS lymphoma, progressive multifocal leukoencephalopathy, Cryptococcoma, cytochrome P4502D6, CYP2D6, P-glycoprotein efflux transport, receptor imaging indicators
Abstract: We describe the details of the magnetic resonance spectroscopy and chemical shift imaging techniques for the human brain which have been developed over the last two decades. With these non-invasive tools, it is now readily possible to repeatedly assay up to 20 common brain metabolites. From the perspective of drug discovery, each of these metabolites could fulfill a number of useful functions: disease biomarker, surrogate marker of drug delivery, surrogate marker of drug efficacy and so on. To facilitate the possible utility of clinical magnetic resonance spectroscopy in future drug discovery, the major portion of the review is devoted to a detailed description of the well-validated neurochemical profiles of many common human brain disorders, for which MRS data now exists. Beyond proton, MRS, the commonest tool provided by the manufacturers of clinical MRI equipment, lays the world of heteronuclear NMR more familiar to chemists. Here too, with relatively little effort it has been possible to define neurochemical profiles of human brain disorders using 13C MRS. The future for drug discovery scientists is discussed. Finally, recognizing that a known feature of MR is the lack of sensitivity, we describe new efforts to harness hyperpolarization, with its 50,000 signal amplification, to conventional MRS.
Export Options
About this article
Cite this article as:
Ross Brian, Tran Thao, Bhattacharya Pratip, Martin Watterson D. and Sailasuta Napapon, Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery, Current Topics in Medicinal Chemistry 2011; 11 (1) . https://dx.doi.org/10.2174/156802611793611850
DOI https://dx.doi.org/10.2174/156802611793611850 |
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
-
Antioxidant Therapy Against Trypanosome Infections: A Review Update
Current Topics in Medicinal Chemistry Pathophysiology of Idiopathic Atrial Fibrillation - Prognostic and Treatment Implications
Current Pharmaceutical Design Metabolomic and Imaging: A Literature Review
Current Medical Imaging Cardiac Stem Cell Regeneration in Metabolic Syndrome
Current Pharmaceutical Design Diabetes and Chronic Heart Failure: From Diabetic Cardiomyopathy to Therapeutic Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets Intestinal Dysbiosis, Gut Hyperpermeability and Bacterial Translocation: Missing Links Between Depression, Obesity and Type 2 Diabetes
Current Pharmaceutical Design Churg-Strauss Syndrome Presenting as Acute Necrotizing Eosinophilic Myocarditis: Concise Review of the Literature
Current Hypertension Reviews Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases
Current Neurovascular Research Anemia and Chronic Kidney Disease: Making Sense of the Recent Trials
Reviews on Recent Clinical Trials CD147 Interacts with NDUFS6 in Regulating Mitochondrial Complex I Activity and the Mitochondrial Apoptotic Pathway in Human Malignant Melanoma Cells
Current Molecular Medicine A Novel Long-circulating DOX Liposome: Formulation and Pharmacokinetics Studies
Pharmaceutical Nanotechnology RAAS Inhibition and Cardiorenal Syndrome
Current Hypertension Reviews Glucose Intolerance and Diabetes Mellitus in Endocrine Disorders – Two Case Reports and a Review
Current Diabetes Reviews Pharmacology of TRP Channels in the Vasculature
Current Vascular Pharmacology NAD+, Sirtuins, and Cardiovascular Disease
Current Pharmaceutical Design The Quest for Novel Biomarkers in Early Diagnosis of Diabetic Neuropathy
Current Proteomics Peroxisome Proliferator-Activated Receptors and the Control of Fatty Acid Oxidation in Cardiac Hypertrophy
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic:Applications of Angiotensin Converting Enzyme Inhibitors and of Angiotensin II Receptor Blockers in Pharmacology and Therapy: An Update (Executive Editor: Agostino Molteni)]
Current Pharmaceutical Design Meet Our Editorial Board Member:
Applied Clinical Research, Clinical Trials and Regulatory Affairs PET Imaging of Beta-Adrenoceptors in Human Brain: A Realistic Goal or a Mirage?
Current Pharmaceutical Design