Download or read book Synthesis of Novel Nitric Oxide Donors and Prodrugs of 5 fluorouracil written by Tingwei Cai and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: This dissertation describes my Ph. D. work that focused on the synthesis and evaluation of novel nitric oxide donors, and the synthesis of derivatives of 5-fluorouracil. In chapter 1, a series of alkyl and aryl N-hydroxyguanidines were synthesized and demonstrated to act as substrates of nitric oxide synthases (NOS). The discovery of these non-amino acid hydroxyguanidines as novel substrates also led to the discovery of a novel-binding mode of NOS. In chapter 2, in order to achieve site specific delivery of nitric oxide (NO), a new class of glycosidase activated NO donors has been developed. Glucose and galactose were covalently coupled to 3-morphorlinosydnonimine (SIN-1), a mesoionic heterocyclic NO donor, via a carbamate linkage at the anomeric position. The beta-glycosides were successfully prepared for these conjugates, while the alfa glycosidic compounds were very unstable. The new stable sugar-NO conjugates could release NO in the presence of glycosidases. Such NO prodrugs may be used as enzyme activated NO donors in biomedical research. In chapter 3, a new sialated diazeniumdiolate has been synthesized and the glycosylation product was exclusively an alfa anomer. This new nitric oxide donor exhibited significantly improved stability as compared to its parent diazeniumdiolate salts and it could be efficiently hydrolyzed by neuraminidase to release nitric oxide with a Km of 0.14 mM. The sialic acid-NO conjugate would be a valuable prodrug that targets NO to influenza viruses. In chapter 4, two classes of prodrugs of 5-fluorouracil (FU) were synthesized. The first type is FU-NO conjugate. The synthesized compounds showed greater cytotoxicities than 5-fluorouracil for DU 145 human prostate and HeLa cancer cells. The second type is carbohydrate-FU conjugate. A new reverse glycosadition was also developed to prepare sugar conjugates. In chapter 5, 7-carboxylindazole, as well as 5- and 6-carboxylindazoles was synthesized. These compounds were designed as isosteres of 7-nitroindazole, a well-known inhibitor of NOS. However, they did not show potent inhibition to NOS.
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2005 with total page 768 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Nitric Oxide NO and Cancer written by Benjamin Bonavida and published by Springer Science & Business Media. This book was released on 2010-06-16 with total page 510 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nitric Oxide (NO) is a pleitropic, ubiquitous modulator of cellular functions. Aryl nitrite and glyceryl trinitrate, representative intravasadilators, were introduced as therapeutic agents more than a century ago for relief from acute attacks of angina. The vasodilator action is mediated by the release of NO following treatment. NO has important therapeutic applications in several diseases such as inflammatory diseases, erectile dysfunction, inflammation, pain and neural protective activity. However, the role of NO in cancer and its application in therapy has received little attention. This monograph will be the first to focus on studies that investigate the role of NO in tumor cell pathogenesis, growth, angiogenesis, response to cytotoxic therapies and NO translational applications in cancer therapy, alone or in conjunction with other therapies.
Download or read book Nitric Oxide Donors written by Amedea Seabra and published by Academic Press. This book was released on 2017-03-17 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nitric Oxide Donors: Biomedical Applications and Perspectives presents the current state of art, challenges and innovations in the design of therapeutics nitric oxide donors with great impact in several aspects of human physiology and pathophysiology. Although considerable innovative progress has been achieved using Nitric Oxide donors in biomedical applications, certain drawbacks still need to be overcome to successfully translate these research innovations into clinical applications. This book encompasses several topics on nitric oxide such as its sources and biological properties; its performance in the cardiovascular and neurologic systems, in the human skin and its application in the treatment of neglected diseases, neurodegenerative disorders, and cancer. Additionally, it covers its role in inflammation and immunity, penile erection function, photodynamic therapy, antimicrobial activities. It also discusses the future of nitric oxide donors in combination with other therapeutic drugs, in implantable sensors, and nitric oxide releasing hydrogels and medical devices for topical applications. The book is a valuable source for researchers on different areas of biomedical field who are interested in the improvements that these molecules can make in the treatment of several conditions. - Provides background information about biology and chemistry of nitric oxide - Discusses the state-of-the-art in the design of nitric oxide releasing nanomaterials for biomedical applications - Covers the usage of nitric oxide donors in the treatment of several conditions, such as cancer, human skin, cardiovascular system, and immunity - Discusses the future of nitric oxide donors and their FDA approval
Download or read book Vicinal Diaryl Substituted Heterocycles written by M. R. Yadav and published by Elsevier. This book was released on 2018-03-14 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vicinal Diaryl-Substituted Heterocycles: A Gold Mine for the Discovery of Novel Therapeutic Agents draws together all of the key information about these compounds in one place for the first time. Following an informative overview of the importance of these structures to the discovery of potential therapeutic agents, the text goes on to outline the main compound types, with each chapter focusing on the activities of a different structure. Designed to support researchers by consolidating this important information in a single, practical guide, the authors hope to encourage further advancement and development in the discovery of novel therapeutic agents. As flexible building blocks for the production of novel compounds, vicinal diaryl-substituted heterocycles are a rich source of leads for the development of new drugs. Their adaptability means that they can be used to produce structures with a broad range of attractive characteristics, and a large number of vicinal diaryl-substituted heterocyclic compounds have already been synthesized and investigated by medicinal chemists as promising lead molecules. - Collects together details of the key vicinal diaryl-substituted heterocyclic compounds in one place for the first time - Highlights biological activities and SAR of derivatives - Structured practically for ease of navigation between different derivatives
Download or read book Cumulated Index Medicus written by and published by . This book was released on 1996 with total page 1344 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Download or read book Chemical Abstracts written by and published by . This book was released on 2002 with total page 2002 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Targeted Delivery of Small and Macromolecular Drugs written by Ajit S. Narang and published by CRC Press. This book was released on 2010-05-12 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: Site-specific drug delivery and targeting attracts much research interest from both academia and industry, but because of the many challenges faced in the development of these systems, only a handful of targeted therapies have successfully made it into clinical practice. Focusing on the delivery technologies that utilize both systemic and local rou
Download or read book Recent Advancement in Prodrugs written by Kamal Shah and published by CRC Press. This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent Advancement in Prodrugs Drugs used as medicines have many limitations like low chemical stability, aqueous solubility, or oral absorption/bioavailability, rapid presystemic metabolism, toxicity, inadequate site specificity, or poor patient acceptance/compliance (unwanted adverse effects, unacceptable taste or odor, irritation or pain). Prodrugs design is an approach to overcome these limitations. Key features Covers recent advancements in development of prodrugs Presents balanced synthesis and applications of prodrug chemistry Discusses broad spectrum of prodrug categories and outlines industrial applications Reviews prodrugs in cancer nanomedicine, its therapy and treatment Elucidates mathematical models to study the kinetics of prodrugs This book covers recent advances in the design of prodrugs. It contains all the significant recent examples of prodrug chemistry developments and will aid academics and researchers seeking to generate new projects in the field.
Download or read book Index Medicus written by and published by . This book was released on 2004 with total page 2164 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
Download or read book New Frontiers in Organoselenium Compounds written by Eder João Lenardão and published by Springer. This book was released on 2018-06-29 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents recent advances in and perspectives on the use of organoselenium compounds, primarily highlighting the new frontiers in the field of Green Chemistry, their therapeutic and biological relevance and new materials. Throughout its 200 pages, readers will find an updated and comprehensive review of new aspects of organoselenium chemistry and biochemistry. Fully referenced and written in an easy to read style, it offers readers a primary resource for including organoselenium derivatives in their projects. This book will be of interest to specialists, students and researchers involved in a broad range of fields, from synthetic green chemistry to medicinal chemistry and the chemistry of natural products. The connection between organoselenium compounds and green chemistry, despite having only recently emerged, is one of the subjects of this book. The first chapter highlights the use of Se-containing molecules as reagents and catalysts in new green protocols to access important organic transformations. The book provides a wealth of examples of bioactive Se-containing molecules, especially focusing on those with potential therapeutic uses. The second chapter focuses on the state of the art concerning the role of organoselenium compounds as antioxidants, GPx mimics, and derivatives endowed with different bioactive properties. “Organoselenium in nature” is the title of the third chapter, which equips readers with essential information on the main natural organoselenium compounds and where they are found. Selected aspects of the metabolism of selenium in plants and microorganisms are also discussed. In closing, the book includes a chapter dedicated to recent advances concerning the nonbonding interactions between organochalcogen compounds. This is currently a hot topic in selenium chemistry and biochemistry, and here readers will find key insights into the chalcogen bond and its role in the biological activity of organoselenium compounds.
Download or read book Resistance to Photodynamic Therapy in Cancer written by Valentina Rapozzi and published by Springer. This book was released on 2014-12-11 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides a comprehensive review of resistance induced by photodynamic therapy (PDT) in tumor cells. Understanding the underlying mechanisms in this process leads to the improvement of therapeutic modality, in combination with chemotherapy, immunotherapy, and radiotherapy. Photodynamic therapy is a minimally invasive therapeutic procedure that can exert a selective or preferential cytotoxic activity toward malignant cells. The procedure involves administration of an intrinsically non-toxic photosensitizing agent (PS) followed by irradiation at a wavelength corresponding to a visible absorption band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Studies reveal that PDT can be curative, particularly in early stage tumors and this volume explores the potential of PDT, but also reveals strategic approaches to overcome resistance in tumor cells.
Download or read book Prodrugs Design written by Rafik Karaman and published by Nova Science Publishers. This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The prodrug approach is a promising and well established strategy for the development of new entities that possess superior efficacy, selectivity and reduced toxicity. Hence an optimised therapeutic outcome can be accomplished using this approach. Prodrug design is becoming more elaborate in the development of efficient and selective drug delivery systems. The targeted prodrug approach, in combination with gene delivery and controlled expression of enzymes and carrier proteins, is a promising strategy for precise and efficient drug delivery and enhancement of the therapeutic effect. This book describes in details all prodrug approaches and examples of prodrugs that succeeded to enter the market. There are two major prodrug design approaches that are considered as widely used among all other approaches: the targeted drug design approach by which prodrugs can be designed to target specific enzymes or carriers by considering enzyme-substrate specificity or carrier-substrate specificity in order to overcome various undesirable drug properties. Examples for such approach is the antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), virus-directed enzyme prodrug therapy (VDEPT) and GDEPT. In addition, this book describes in details a novel prodrug chemical approach which is based on intramolecular reactions that were utilised to understand how enzymes exert their high catalysis. The information gained from the experimental and theoretical calculations on these enzyme models was used to design efficient chemical moieties to be utilised as prodrug linkers with the potential to release the corresponding parent drugs in a slow or fast release manner. Several prodrugs for commonly used drugs suffer from low bioavailability or/and bitter sensation were designed using quantum mechanics methods (DFT and ab initio) and recently a large number among these prodrugs were synthesised. Examples of such prodrugs are presented in the different chapters of the book.
Download or read book Multimodal Concepts for Integration of Cytotoxic Drugs written by Martin J. Brown and published by Springer Science & Business Media. This book was released on 2006-08-06 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first part of this book summarizes the rationale and the preclinical data for combined treatment with ionizing radiation and pharmaceutical agents. Individual chapters focus on forms of combined treatment, with due consideration being given to a range of drugs and to emerging combinations with small molecules and antibodies. The second part comprises a series of disease-specific chapters in which the clinical results of combined modality treatment are presented.
Download or read book Integration of Pharmaceutical Discovery and Development written by Ronald T. Borchardt and published by Springer Science & Business Media. This book was released on 2006-01-19 with total page 627 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and metabolic/pharmacokinetic (e. g. , metabolic stability, clearance, and protein binding) properties. Successful implementation of this strategy requires a multidisciplinary team effort, incl- ing scientists from drug design (e. g. , medicinal chemists, cell biologists, en- mologists, pharmacologists) and drug development (e. g. , analytical chemists, pharmaceutical scientists, physiologists, and molecular biologists representing the disciplines of pharmaceutics, biopharmaceutics, and pharmacokinetics/drug metabolism). With this new, highly integrated approach to drug design now widely utilized by the pharmaceutical industry, the editors of this book have provided the sci- tific community with case histories to illustrate the nature of the interdisciplinary interactions necessary to successfully implement this new approach to drug d- covery. In the first chapter, Ralph Hirschmann provides a historical perspective of why this paradigm shift in drug discovery has occurred.
Download or read book Modern Applications of Cycloaddition Chemistry written by Paolo Quadrelli and published by Elsevier. This book was released on 2019-03-20 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Modern Applications of Cycloaddition Chemistry examines this area of organic chemistry, with special attention paid to cycloadditions in synthetic and mechanistic applications in modern organic chemistry. While many books dedicated to cycloaddition reactions deal with the synthesis of heterocycles, general applications, specific applications in natural product synthesis, and the use of a class of organic compounds, this work sheds new light on pericyclic reactions by demonstrating how these valuable tools elegantly solve synthetic and mechanistic problems. The work examines how pericyclic reactions have been extensively applied to different chemistry areas, such as chemical biology, biological processes, catalyzed cycloaddition reactions, and more. This work will be useful for organic chemists who deal with organic chemistry, medicinal chemistry, agrochemistry and material chemistry. - Provides details on the synthesis of antiviral and anticancer compounds, marking the key role of unconventional catalyzed cycloaddition reactions for preparing new derivatives in a unique reaction pathway that is scalable in industrial processes - Contains the most up-to-date review of the use of pericyclic reactions in drug delivery - Includes the enzyme-catalyzed processes involving cycloaddition reactions for different targets, demonstrating that cycloaddition is more common in nature than expected - Features new applications for cycloadditions in material chemistry and provides a general view of the most recent results in the area
