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Alzheimer’s disease (AD) is characterized by two main protein aggregate hallmarks in the brain: extracellular deposition of the amyloid-? (A?) in senile plaques and intracellular neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau protein. The past decade has seen great progress in the development of imaging probes for the non-invasive detection of A? and tau aggregates. Here positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), are highly promising technologies for clinical diagnostics. However, as a research tool, optical imaging is superior because it is real-time, sensitive, inexpensive, not radioactive and that it in particular affords high-resolution studies both in vitro and in vivo. Fluorescent probes are especially useful for designing novel binding scaffolds for structure investigations of protein aggregates. This thesis describes design, synthesis and evaluation of a series of fluorescent probes for detection of amyloid fibrils, especially A? or tau aggregates in vitro. Firstly, trans-stilbenoid vinylbenzene-1,2-diol with benzene, naphthalene, anthracene, and pyrene are investigated with respect to their photophysical properties free in solution and when bound to amyloid fibrils, including time-resolved fluorescence measurements. It is noted that the extended conjugated systems retained the amyloid targeting properties of the probes and both the anthracene and pyrene moieties extensively enhanced the fluorescence intensity and prolonged lifetimes. Secondly, the synthesis of two molecules, Py1SA and Py2SA, based on pyrene linked to salicylic acid via a trans-stilbene C = C bond is presented. The compounds show strikingly different emission spectra when bound to preformed A?1-42 fibrils as well as to fibrils from four other distinct proteins. Additionally, excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) is observed for the anionic form of the probes in polar solvents. This is likely the reason for the spectral differences of the probes when bound to amyloid fibrils. Moreover, the synthesis of a further development of the Congo red analogue X-34 [2,5-bis(4’-hydroxy-3’-carboxy-styryl) benzene] by rational design and synthesis is described. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of A?1-42 and tau as well as selectivity towards the corresponding disease-associated protein aggregates in human post mortem AD tissue. Lastly, the synthesis of a set of 2,1,3-benzothiadiazole (BTD)-based ligands with different conjugated spacers and variable patterns of OH substitutions of bis-styryl-BTD prototypes were developed. A? binding affinities (A?1-42 and A?1-40 fibrils) and the specificity towards A? plaques of all ligands were determined. These findings extend the structure to activity relationships of BTD-based ligands for A? fibril binding. Throughout the studies in this dissertation, new interesting properties of small molecule fluorescence probes have been discovered and analyzed. This knowledge should facilitate the development of noninvasive probes for early detection of Alzheimer's disease and to distinguish different A? fibril polymorphs.
Coumarins are widely distributed in nature and can be found in a large number of naturally occurring and synthetic bioactive molecules. The unique and versatile oxygen-containing heterocyclic structure makes them a privileged scaffold in Medicinal Chemistry. Many coumarin derivatives have been extracted from natural sources, designed, synthetized, and evaluated on different pharmacological targets. In addition, coumarin-based ion receptors, fluorescent probes, and biological stains are growing quickly and have extensive applications to monitor timely enzyme activity, complex biological events, as well as accurate pharmacological and pharmacokinetic properties in living cells. The extraction, synthesis, and biological evaluation of coumarins have become extremely attractive and rapidly developing topics. A large number of research and review papers have compiled information on this important family of compounds in 2020. Research articles, reviews, communications, and concept papers focused on the multidisciplinary profile of coumarins, highlighting natural sources, most recent synthetic pathways, along with the main biological applications and theoretical studies, were the main focus of this book. The huge and growing range of applications of coumarins described in this book is a demonstration of the potential of this family of compounds in Organic Chemistry, Medicinal Chemistry, and different sciences related to the study of natural products. This book includes 23 articles: 17 original papers and six review papers.
The third edition of this established classic text reference builds upon the strengths of its very popular predecessors. Organized as a broadly useful textbook Principles of Fluorescence Spectroscopy, 3rd edition maintains its emphasis on basics, while updating the examples to include recent results from the scientific literature. The third edition includes new chapters on single molecule detection, fluorescence correlation spectroscopy, novel probes and radiative decay engineering. Includes a link to Springer Extras to download files reproducing all book artwork, for easy use in lecture slides. This is an essential volume for students, researchers, and industry professionals in biophysics, biochemistry, biotechnology, bioengineering, biology and medicine.
Comparative Diagnostic Pharmacology: Clinical and Research Applications in Living-System Models is the first evidence-based reference text devoted exclusively to the subject of applying pharmaceutical and biopharmaceutical agents as diagnostic probes in clinical medicine and investigative research.This unique and groundbreaking book is a versatile guide for clinicians and researchers interested in using pharmacologic agents to: Diagnose disease Assess physiological processes Identify the appropriateness of a therapeutic agent Determine appropriate dosing for therapeutic use. Extensively referenced and organized by major body systems, individual topics are listed in an evidence-based format according to specific disease processes or physiological processes of interest. Each entry also includes information on the mechanism of action, administration, and diagnostic interpretation. Descriptions have been provided for the application of diagnostic pharmaceuticals to assess a wide spectrum of diseases and physiological processes relevant to the fields of veterinary and human medicine. Comparative Diagnostic Pharmacology is useful not merely for pharmaceutical-oriented research investigations, but it will also prove invaluable for the monitoring and evaluation of physiological responses and disease processes in animal models.
With contributions by numerous experts
An increasingly aging population will add to the number of individuals suffering from amyloid. Protein Misfolding Diseases provides a systematic overview of the current and emerging therapies for these types of protein misfolding diseases, including Alzheimer's, Parkinson's, and Mad Cow. The book emphasizes therapeutics in an amyloid disease context to help students, faculty, scientific researchers, and doctors working with protein misfolding diseases bridge the gap between basic science and pharmaceutical applications to protein misfolding disease.
While there is a nearly universal agreement that drinking tea can benefit health, information on the benefits or adverse effects of drinking tea is scattered, leaving definitive answers difficult to ascertain. Tea in Health and Disease Prevention, Second Edition, once again addresses this problem, bringing together all the latest and most relevant information on tea and its health effects into one comprehensive resource. This book covers compounds in black, green, and white teas and explores their health implications, first more generally, then in terms of specific organ systems and diseases. With over 75% brand new content, this fully reorganized, updated edition covers a wider range of tea varieties and beneficial compounds found in tea, such as epigallocatechin gallate and antioxidants.Tea in Health and Disease Prevention, Second Edition, is an organized, efficient resource that will help readers find quick answers to questions and will help inspire further studies for those interested in tea research. This is a must-have reference for researchers in food science and nutrition, as well as nutritionists and dieticians. - Covers and compares features, benefits, and potential negative effects of the most important types of tea, including green, black, and white - Identifies therapeutic benefits of teas for new product development - Offers a "one stop shop" for research in this area, compiling both foundational and cutting-edge topics into one resource - Includes a dictionary of key terms, other health effects of tea or extracts, and a summary point section within each chapter for a quick reference
Plants produce a huge array of natural products (secondary metabolites). These compounds have important ecological functions, providing protection against attack by herbivores and microbes and serving as attractants for pollinators and seed-dispersing agents. They may also contribute to competition and invasiveness by suppressing the growth of neighboring plant species (a phenomenon known as allelopathy). Humans exploit natural products as sources of drugs, flavoring agents, fragrances and for a wide range of other applications. Rapid progress has been made in recent years in understanding natural product synthesis, regulation and function and the evolution of metabolic diversity. It is timely to bring this information together with contemporary advances in chemistry, plant biology, ecology, agronomy and human health to provide a comprehensive guide to plant-derived natural products. Plant-derived natural products: synthesis, function and application provides an informative and accessible overview of the different facets of the field, ranging from an introduction to the different classes of natural products through developments in natural product chemistry and biology to ecological interactions and the significance of plant-derived natural products for humans. In the final section of the book a series of chapters on new trends covers metabolic engineering, genome-wide approaches, the metabolic consequences of genetic modification, developments in traditional medicines and nutraceuticals, natural products as leads for drug discovery and novel non-food crops.
This comprehensive volume focuses on anti-inflammatory nutraceuticals and their role in various chronic diseases. Food and Drug Administration (FDA) approved drugs such as steroids, non-steroidal anti-inflammatory drugs (NSAIDS), statins and metformin have been shown to modulate inflammatory pathways, but their long-term intake has been associated with numerous side effects. This means that there is enormous potential for dietary agents that can modulate inflammatory pathways in humans. Leading experts describe the latest research on the role of anti-inflammatory nutraceuticals in preventing and treating chronic diseases.
Recent Advances in Natural Products Analysis is a thorough guide to the latest analytical methods used for identifying and studying bioactive phytochemicals and other natural products. Chemical compounds, such as flavonoids, alkaloids, carotenoids and saponins are examined, highlighting the many techniques for studying their properties. Each chapter is devoted to a compound category, beginning with the underlying chemical properties of the main components followed by techniques of extraction, purification and fractionation, and then techniques of identification and quantification. Biological activities, possible interactions, levels found in plants, the effects of processing, and current and potential industrial applications are also included. - Focuses on the latest analytical techniques used for studying phytochemical and other biological compounds - Authored and edited by the top worldwide experts in their field - Discusses the current and potential applications and predicts future trends of each compound group