Design, Synthesis and Biological Evaluation of New Polyamine Derivatives as Antikinetoplastid Agents

Design, Synthesis and Biological Evaluation of New Polyamine Derivatives as Antikinetoplastid Agents
Author: Elodie Jagu
Publisher:
Total Pages: 0
Release: 2016
Genre:
ISBN:

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This project is at the interface of chemistry and biology and relies on the expertise of two different teams. This thesis involves the design and development of inhibitors directed against Kinetoplastids. It is urgent to develop new therapeutic strategies to respond to drug resistance and toxicity of currently used drugs against these parasites. Polyamine metabolism and transporter have been demonstrated as essential for parasite growth. Therefore, these systems are potential drug targets for development of antikinetoplastid compounds. We chose to synthesize polyamine derivatives and evaluate their biological activity against Kinetoplatids. Fifty-four compounds, divided into three chemical series, have been synthesized and evaluated. Many have shown a micromolar biological activity in vitro against parasite. In vivo evaluation is foreseen for the most promising derivative.

Challenges in Delivery of Therapeutic Genomics and Proteomics

Challenges in Delivery of Therapeutic Genomics and Proteomics
Author: Ambikanandan Misra
Publisher: Elsevier
Total Pages: 686
Release: 2010-09-09
Genre: Science
ISBN: 0123849659

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Delivery of therapeutic proteomics and genomics represent an important area of drug delivery research. Genomics and proteomics approaches could be used to direct drug development processes by unearthing pathways involved in disease pathogenesis where intervention may be most successful. This book describes the basics of genomics and proteomics and highlights the various chemical, physical and biological approaches to protein and gene delivery. Covers a diverse array of topics from basic sciences to therapeutic applications of proteomics and genomics delivery Of interest to researchers in both academia and industry Highlights what’s currently known and where further research is needed

Investing to Overcome the Global Impact of Neglected Tropical Diseases

Investing to Overcome the Global Impact of Neglected Tropical Diseases
Author: World Health Organization
Publisher: World Health Organization
Total Pages: 211
Release: 2015-08-05
Genre: Medical
ISBN: 9241564865

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"The presence, or absence, of neglected tropical diseases (NTDs) can be seen as a proxy for poverty and for the success of interventions aimed at reducing poverty. Today, coverage of the public-health interventions recommended by the World Health Organization (WHO) against NTDs may be interpreted as a proxy for universal health coverage and shared prosperity - in short, a proxy for coverage against neglect. As the world's focus shifts from development to sustainable development, from poverty eradication to shared prosperity, and from disease-specific goals to universal health coverage, control of NTDs will assume an important role towards the target of achieving universal health coverage, including individual financial risk protection. Success in overcoming NTDs is a "litmus test" for universal health coverage against NTDs in endemic countries. The first WHO report on NTDs (2010) set the scene by presenting the evidence for how these interventions had produced results. The second report (2013) assessed the progress made in deploying them and detailed the obstacles to their implementation. This third report analyses for the first time the investments needed to achieve the scale up of implementation required to achieve the targets of the WHO Roadmap on NTDs and universal coverage against NTDs. INVESTING TO OVERCOME THE GLOBAL IMPACT OF NEGLECTED TROPICAL DISEASES presents an investment strategy for NTDs and analyses the specific investment case for prevention, control, elimination and eradication of 12 of the 17 NTDs. Such an analysis is justified following the adoption by the Sixty-sixth World Health Assembly in 2013 of resolution WHA6612 on neglected tropical diseases, which called for sufficient and predictable funding to achieve the Roadmap's targets and sustain control efforts. The report cautions, however, that it is wise investment and not investment alone that will yield success. The report registers progress and challenges and signals those that lie ahead. Climate change is expected to increase the spread of several vector-borne NTDs, notably dengue, transmission of which is directly influenced by temperature, rainfall, relative humidity and climate variability primarily through their effects on the vector. Investments in vector-borne diseases will avoid the potentially catastrophic expenditures associated with their control. The presence of NTDs will thereby signal an early warning system for climate-sensitive diseases. The ultimate goal is to deliver enhanced and equitable interventions to the most marginalized populations in the context of a changing public-health and investment landscape to ensure that all peoples affected by NTDs have an opportunity to lead healthier and wealthier lives."--Publisher's description.

Polyamines

Polyamines
Author: Anthony E. Pegg
Publisher: Humana Press
Total Pages: 524
Release: 2011-04-06
Genre: Science
ISBN: 9781617790355

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Recently, important new findings in the polyamine field and a variety of new experimental systems have revolutionized the study of these ubiquitous cellular components, essential for normal growth and development. In Polyamines: Methods and Protocols, leading researchers contribute an extensive collection of up-to-date laboratory techniques for the further pursuit of polyamine study. The volume delves into vital subjects such as neoplasia studies with animal models and human patients, therapeutic roles for polyamine inhibitors and analogs, polyamine metabolism and oxidative damage, polyamines as regulators of critical ion channels, as well as polyamine transport systems and polyamine-responsive genes. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and expert notes on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Polyamines: Methods and Protocols provides a key resource for all scientists pursuing the study of this dynamic and significant aspect of cellular biology.

Molecules to Medicine with mTOR

Molecules to Medicine with mTOR
Author: Kenneth Maiese
Publisher: Academic Press
Total Pages: 474
Release: 2016-02-21
Genre: Science
ISBN: 012802755X

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Molecules to Medicine with mTOR: Translating Critical Pathways into Novel Therapeutic Strategies is a one-stop reference that thoroughly covers the mechanistic target of rapamycin (mTOR). mTOR, also known as the mammalian target of rapamycin, is a 289-kDa serine/threonine protein kinase that is ubiquitous throughout the body and has a critical role in gene transcription and protein formation, stem cell development, cell survival and senescence, aging, immunity, tissue regeneration and repair, metabolism, tumorigenesis, oxidative stress, and pathways of programmed cell death that include apoptosis and autophagy. Incorporating a translational medicine approach, this important reference highlights the basic cellular biology of mTOR pathways, presents the role of mTOR during normal physiologic function and disease, and illustrates how the mechanisms of mTOR can be targeted for current and future therapeutic treatment strategies. Coverage of mTOR signaling includes the entire life cycle of cells that impacts multiple systems of the body including those of nervous, cardiovascular, immune, musculoskeletal, endocrine, reproductive, renal, and respiratory origin. Covers the role of mTOR by internationally recognized expert contributors in the field. Provides a clear picture of the complexity of mTOR signaling as well as of the different approaches that could target this pathway at various levels. Includes analysis of the role of mTOR and in both health and disease. Serves as an important resource for a broad audience of healthcare providers, scientists, drug developers, and students in both clinical and research settings.

DNA Methylation and Complex Human Disease

DNA Methylation and Complex Human Disease
Author: Michel Neidhart
Publisher: Academic Press
Total Pages: 546
Release: 2015-08-11
Genre: Science
ISBN: 0127999205

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DNA Methylation and Complex Human Disease reviews the possibilities of methyl-group-based epigenetic biomarkers of major diseases, tailored epigenetic therapies, and the future uses of high-throughput methylome technologies. This volume includes many pertinent advances in disease-bearing research, including obesity, type II diabetes, schizophrenia, and autoimmunity. DNA methylation is also discussed as a plasma and serum test for non-invasive screening, diagnostic and prognostic tests, as compared to biopsy-driven gene expression analysis, factors which have led to the use of DNA methylation as a potential tool for determining cancer risk, and diagnosis between benign and malignant disease. Therapies are at the heart of this volume and the possibilities of DNA demethylation. In cancer, unlike genetic mutations, DNA methylation and histone modifications are reversible and thus have shown great potential in the race for effective treatments. In addition, the authors present the importance of high-throughput methylome analysis, not only in cancer, but also in non-neoplastic diseases such as rheumatoid arthritis. Discusses breaking biomarker research in major disease families of current health concern and research interest, including obesity, type II diabetes, schizophrenia, and autoimmunity Summarizes advances not only relevant to cancer, but also in non-neoplastic disease, currently an emerging field Describes wholly new concepts, including the linking of metabolic pathways with epigenetics Provides translational researchers with the knowledge of both basic research and clinic applications of DNA methylation in human diseases

Drug Targets in Kinetoplastid Parasites

Drug Targets in Kinetoplastid Parasites
Author: Hemanta K. Majumder
Publisher: Springer
Total Pages: 0
Release: 2011-01-24
Genre: Medical
ISBN: 9781441926562

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The dreaded protozoal diseases caused by a number of Kinetoplastid parasites threaten mankind, as therapeutic tools for the treatment of most parasitic diseases are extremely limited. Development of commercially available vaccines is still far from reality, though research and trial programs continue. This book covers current research into drug therapeutics for the conditions caused by the parasites, which if viewed globally, pose an increasing threat to human health and welfare.

Polyamine Drug Discovery

Polyamine Drug Discovery
Author: Patrick Woster
Publisher: Royal Society of Chemistry
Total Pages: 303
Release: 2011-11-07
Genre: Medical
ISBN: 1849733090

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Polyamines are ubiquitous molecules that are involved in a number of important cellular processes. Aberrations in their function or metabolism play a role in diseases such as cancer and parasitic infection. A number of validated drug targets have been identified, including enzymes in the polyamine biosynthetic and catabolic pathways and the S-adenosylmethionine synthetic and salvage pathways. Polyamine Drug Discovery is the first comprehensive volume to cover all aspects of the design and development of potential therapeutics targeting polyamine metabolism. The book details research progress from 1975 to the present date and discusses the design and use of polyamine metabolism inhibitors as therapeutic agents. Various polyamine-containing drugs are described that can be used in chemotherapy, and as treatments for infections including trypanosomiasis, leishmaniasis and malaria. Finally, the roles of polyamine analogues in chemoprevention, polyamine-containing vectors for gene delivery, and the design of polyamine-based epigenetic modulators are detailed. Each chapter addresses a different aspect of polyamine drug discovery and all are written by medicinal and biological chemists with particular expertise in developing agents that modulate polyamine metabolism or function. The book will increase the visibility of polyamine drug discovery among pharmaceutical researchers and provide a valuable reference for everyone working in the field.

Nanostructures for Drug Delivery

Nanostructures for Drug Delivery
Author: Ecaterina Andronescu
Publisher: Elsevier
Total Pages: 1026
Release: 2017-03-24
Genre: Technology & Engineering
ISBN: 0323461492

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Nanostructures for Drug Delivery extensively covers the various nanostructured products that have been tested as carriers in target drug delivery systems. In addition, the book analyses the advantages of, and issues related to, using nanostructured materials in drug delivery systems, also detailing various nanocarrier preparation techniques. As delivering the drug to the target site is a major problem in providing effective treatment for many diseases, this book covers the latest advancements in numerous nanotechnological products that are being used in disease detection, controlled drug delivery, as biosensors, and in tissue engineering that have been developed for more efficient patient healthcare. Due to the versatility of nanostructured materials, it is now possible to deliver a drug at its target site in a more accurate and efficient way. This volume is an up-to-date, state-of-the-art work that highlights the principal mechanistic aspects related to the delivery of active nanoscale therapeutic agents (natural or synthetic) and their release profile in different environmental media. It highlights nanoscale encapsulation strategies and discusses both organic and inorganic nanomaterials as carriers and delivery platforms. Demonstrates how nanostructures are successfully employed in drug delivery stems and as drug delivery agents, allowing biomaterials scientists and biochemists to create more effective drug delivery systems Offers an overview of recent research into the use of nanostructures in drug delivery techniques in a cogent, synthesized way, allowing readers to quickly familiarize themselves with this area Includes examples of how the application of nanostructures have improved the efficiency of drug delivery systems, showing medical scientists how they are beneficial

Metabolic Interaction in Infection

Metabolic Interaction in Infection
Author: Ricardo Silvestre
Publisher: Springer
Total Pages: 478
Release: 2018-04-06
Genre: Science
ISBN: 3319749323

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This book focuses on host–pathogen interactions at the metabolic level. It explores the metabolic requirements of the infectious agents, the microbial metabolic pathways that are dedicated to circumvent host immune mechanisms as well as the molecular mechanisms by which pathogens hijack host cell metabolism for their own benefit. Finally, it provides insights on the possible clinical and immunotherapeutic applications, as well as on the available experimental and analytical methods. The contributions break new ground in understanding the metabolic crosstalk between host and pathogen.