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This book comprehensively reviews current and novel treatment strategies against human parasites, including protozoans and helminths, using natural products. The initial chapters summarize the conventional treatment strategies and natural-product based therapeutics against these parasites. It discusses biochemical tools and techniques for the discovery of natural product based drugs against human parasites. The book also covers the ingenious and innovative mechanisms to achieve drug resistance by the protozoan parasites and strategies to overcome the resistance. It entails mechanistic insight into the modulation of host immune responses to delay or inhibit parasite clearance and explores host-pathogen interactions that mediate immunity against subsequent parasite challenge. In turn, the volume helps in understanding the immunobiology of the parasites and tools to identify candidate vaccine antigens and novel delivery systems against the protozoan parasites. Lastly, it explores the role of advanced methods, including nanotechnology, marine bioprospecting, and microorganisms-derived biochemicals against the protozoan parasites. This book is useful for students and researchers of pharmacology, parasitology, zoology and other allied fields.​
Natural Products have been important sources of useful drugs from prehistoric times to the present. This book gives an overview about this field and provides important recent contributions to the discovery of new drugs generated by research on natural products. Total synthesis of natural products with interesting biological activities is paving the way for the preparation of new and improved analogs. The methods of combinatorial chemistry permit the selection of the best drug from a large number of candidates. Beyond synthesis and evaluation of organic molecules a number of new bioorganic methods are coming to the fore and will be discucced in this isue of the ERnst schering Research Foundation workshop proceedings.
One of the top four contributors to the global burden of disease is diarrheal infections. Intestinal parasites are major causes of morbidity and mortality associated with diarrheal diseases in both the developed and developing world. Amebiasis is responsible for 50 million cases of invasive disease and 70,000 deaths annually in the world. Giardiasis has an estimated worldwide prevalence of 280 million cases annually. In developed countries, Giardia lamblia infects about 2% of adults and 6-8% of children. The prevalence of G. lamblia infection is generally higher in developing countries, ranging from 3% to 90%. Furthermore, giardial infections contribute substantially to the 2.5 million annual deaths from diarrheal disease. In Asia, Africa, and Latin America, about 500,000 new giardiasis cases are reported each year. Cryptosporidium accounts for 20% and 9% of diarrheal episodes in children in developing and developed countries, respectively. Infection with Cryptosporidium can be chronic and especially debilitating in immunosuppressed individuals and malnourished children. A recent study to measure disease burden, based on disability-adjusted life years (DALYs), found that cryptosporidiosis and amebiasis produce about 10.6 million DALYs. This exceeds the DALYs of any helminth infection currently being targeted by the World Health Organization for preventive chemotherapy. Because of its link with poverty, Giardia and Cryptosporidium were included in the WHO Neglected Diseases Initiative in 2004. E. histolytica, G. lamblia, and C. parvum have been listed by the National Institutes of Health (NIH) as category B priority biodefense pathogens due to low infectious dose and potential for dissemination through compromised food and water supplies in the United States. Despite the prevalence of amebiasis, giardiasis, and cryptosporidiosis there are no vaccines or prophylactic drugs. The first-line drugs for invasive amebiasis and giardiasis chemotherapy are nitroimidazoles, with the prototype, metronidazole, being the most common drug used worldwide. Metronidazole has been shown to be both mutagenic in a microbiological system and carcinogenic to rodents, and frequently causes gastrointestinal side effects. In spite of the efficacy of nitroimidazole drugs, treatment failures in giardiasis occur in up to 20% of cases. Clinical resistance of G. lamblia to metronidazole is proven and cross resistance is a concern with all commonly used antigiardial drugs. Nitazoxanide, the only FDA-approved drug for the treatment of cryptosporidiosis, is effective in the treatment of immunocompetent patients and partially effective for immunosuppressed patients. Therefore, it is critical to search for more effective drugs to treat amebiasis, giardiasis, and cryptosporidiosis. This Research Topic for Frontiers in Microbiology will explore the recent progress in drug development for parasitic diarrheal diseases. This includes an understanding of drug resistance mechanisms. We would also welcome submissions on the drug development for other diarrheal parasites. We hope that this research topic will include a comprehensive survey of various attempts by the parasitology research community to create effective drugs for these diseases.
Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Philip Rosenthal, MD, and a panel of leading malaria experts drawn from academia, the military, and international health organizations survey the latest scientific understanding of antimalarial chemotherapy, emphasizing the molecular mechanisms of resistance and the description of important new targets. Their survey covers the current status of malarial and antimalarial chemotherapy, the relevant biology and biochemistry of malaria parasites, the antimalarial drugs currently available, new chemical approaches to chemotherapy, and possible new targets for chemotherapy. Comprehensive and cutting-edge, Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery clearly delineates all the basic and clinical research now addressing one of the world's major unresolved disease problems, work that is now powerfully driving the rapid pace of antimalarial drug discovery today.
This well illustrated book provides an historical and unified overview of a century and a half of research on the development, life cycles, transmission and evolution of the nematodes found in vertebrates throughout the world. This second, expanded edition includes relevant data from some 450 new references that have appeared from 1989 to 1999. The volume includes nematode parasites of humans, domestic animals and wildlife including fish. After an introductory chapter outlining general principles, the author systematically describes the biological characteristics of the 27 superfamilies of nematodes, followed by families, subfamilies, genera and species.
For human health, leishmaniasis is among the most important protozoan diseases, superseded only by malaria. Globally, 10 to 12 million people are infected with 1.5 million new cases every year. The development of cheaper new drugs is urgently needed for this neglected disease that is developing resistance to current treatments. Chemotherapy remains the only treatment option for the bulk of patients. However, this is largely unaffordable for most. In the past three years numerous advances in drug discovery have been made for treating this disease by exploiting diverging metabolic pathways between the Leishmania enzymes and their hosts, using nanotechnology to target the immune cell phagolysosomes where Leishmania resides. Drug Discovery for Leishmaniasis aims to provide a perspective of the current treatments and their challenges, blended with the emerging strategies and methodologies that will drive new target appraisals and drug developments, as well as addressing the molecular basis of resistance in Leishmania. Recent studies have shown that leishmaniasis affects some of the poorest people in the world, with 95% of fatal cases occurring in only 6 countries. With the WHO goal of eliminating this public health problem in the South-east Asia Region by 2020, this book will be important for anyone who is interested in neglected tropical diseases.
Introduction to Fragment-Based Drug Discovery, by Daniel A. Erlanson Fragment Screening Using X-Ray Crystallography, by Thomas G. Davies and Ian J. Tickle Hsp90 Inhibitors and Drugs from Fragment and Virtual Screening, by Stephen Roughley, Lisa Wright, Paul Brough, Andrew Massey and Roderick E. Hubbard Combining NMR and X-ray Crystallography in Fragment-Based Drug Discovery: Discovery of Highly Potent and Selective BACE-1 Inhibitors, by Daniel F. Wyss, Yu-Sen Wang, Hugh L. Eaton, Corey Strickland, Johannes H. Voigt, Zhaoning Zhu and Andrew W. Stamford Combining Biophysical Screening and X-Ray Crystallography for Fragment-Based Drug Discovery, by Michael Hennig, Armin Ruf and Walter Huber Targeting Protein–Protein Interactions and Fragment-Based Drug Discovery, by Eugene Valkov, Tim Sharpe, May Marsh, Sandra Greive and Marko Hyvönen Fragment Screening and HIV Therapeutics, by Joseph D. Bauman, Disha Patel and Eddy Arnold Fragment-Based Approaches and Computer-Aided Drug Discovery, by Didier Rognan
One of the main problems concerning therapeutic tools for the treatment of parasitic diseases, including leishmaniasis, is that some field parasites are naturally resistant to the classical drugs; additionally, current therapies may select parasites prone to be resistant to the applied drugs. These features are (at least partially) responsible for the disappointing persistence of the disease and resultant deaths worldwide. This book provides a comprehensive view of the pathology of the disease itself, and of parasitic drug resistance, its molecular basis, consequences and possible treatments. Scientists both from academic fields and from the industry involved in biomedical research and drug design, will find in this book a valuable and fundamental guide that conveys the knowledge needed to understand and to improve the success in combating this disease worldwide.
This volume begins with a short history of malaria and follows with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment, and then describes quinine’s biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine’s structure. It also covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of additional natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature’s combinatorial library is challenging, it is very likely to yield new antimalarial drugs. This book thus ends by identifying ten natural products with development potential as clinical antimalarial agents.