Download or read book Membrane Transporters as Anti malarial Drug Targets written by Fouzi Ismat and published by . This book was released on 2007 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Membrane Transporters and Channels as Targets for Drugs written by Graça Soveral and published by Frontiers Media SA. This book was released on 2020-01-03 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very interestingly, altered expression of transporters has been described in several human pathologies. On this basis, many transport proteins are well acknowledged targets for drugs. Many others are involved in drug delivery and disposition and/or are considered potential targets. Others are off-targets for drugs and then, are responsible for side effects. Thus, membrane protein drug discovery is now an emerging field where the search for physiological mechanisms of regulation and for chemical compounds as modulators of transport activity, present new opportunities for drug development and for new therapies. This Research Topic addresses the latest research advances in membrane transport proteins, stimulating future research on these important protein families.
Download or read book Membrane Transporters as Drug Targets written by Gordon L. Amidon and published by St. Martin's Press. This book was released on 1999-11-30 with total page 572 pages. Available in PDF, EPUB and Kindle. Book excerpt: Because progress in the field of transporters has been extraordinary, this volume will focus on recent advances in our understanding of the structure, function, physiology, and molecular biology of membrane transporters. There will be an emphasis on transporters as molecular targets for drug delivery and disposition in the body.
Download or read book Plasmodium Falciparum Transporters as Antimalarial Drug Targets written by Anne-Catrin Uhlemann and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodiumfalciparum malaria poses one of the most important disease problems in the world. Despite decades of effort to improve disease outcome, the emergence and rapid dissemination of multi-drug resistant parasites has led to a disturbing increase in malaria mortality and morbidity. A critical limitation in managing multi-drug resistant falciparum malaria has been the incomplete understanding of both the underlying molecular mechanisms of drug resistance and the mode of action of widely used drugs. This study aimed to characterise the molecular mechanisms underlying multi- drug resistant malaria by studying the role of gene amplification in the P. falciparum multi-drug resistance gene 1 (pfmdrl) in determining parasite response to a variety of antimalarials in vitro and in vivo. In addition, P. falciparum ATPase 6 (PfATP6), a putative drug target of the widely used artemisinins, was also examined for possible drug-modulating mutations. First a real-time peR technique to measure amplification of pfmdri was developed and validated. This technique was used to determine pfmdri copy number in a unique set of field sample set (n = 600) collected in Northern Thailand, an area harbouring the world's most drug-resistant parasites. This allowed a comprehensive analysis of the importance of pfmdri amplification in (1) in vitro resistance to drugs, (2) in vivo response to mefloquine or mefloquine- artesunate therapy, (3) evolution of amplification in pre- and post-treatment samples. Subsequent studies also investigated the prevalence of pfmdrt amplification in Gabon, a Sub-Saharan country with very little mefloquine resistance. In addition, P. falciparum field isolates were studied for possible polymorphisms in PfATP6 and plasmid constructs generated to study the role of single nucleotide point mutations in the putative active site of the enzyme.
Download or read book Drug Targets for Plasmodium Falciparum Historic to Future Perspectives written by Mohammed Tarique and published by Springer Nature. This book was released on with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Molecular Analysis of Membrane Transporters Implicated in Drug Resistance written by Jacqueline K. Lekostaj and published by ProQuest. This book was released on 2008 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: Resistance to cancer chemotherapeutics and antimalarial drugs is a major obstacle to the successful treatment of these diseases. Membrane transporters have been identified as contributing to this drug resistance. The HuMDR1 protein is thought to reduce accumulation of chemotherapeutics by ATP-dependent transport of the toxic compounds out of the cell. Though previously believed to be a major component of clinical cancer drug resistance, HuMDR1 is now accepted as playing only a minor role, secondary to other mechanisms. The Plasmodium falciparum protein homologue, PfMDR1, may be acting in a similar manner within the malarial parasite, affecting the partitioning of antimalarial drugs amongst cellular compartments. However, the evolving picture of quinoline antimalarial drug resistance may point to a mere modulatory role for PfMDR1 in comparison to another membrane protein, PfCRT, which has been proven to be causative of some drug resistance phenotypes but through an unknown mechanism. Since the protein is native to a subcellular organelle within an intracellular parasite, molecular level analysis of PfMDR1 would benefit from heterologous expression in a simpler system. This thesis reports the successful inducible overexpression of PfMDR1 in Pichia pastoris yeast. The tagged protein can be purified by affinity chromatography and functionally reconstituted in proteoliposomes. ATPase assays of many PfMDR1 variants show the protein to have high basal activity, with very little drug-induced responsiveness. These results support a model in which PfMDR1 acts to modulate the drug resistance profiles determined by PfCRT or to compensate for fitness losses incurred by mutation of PfCRT. All current hypotheses for the molecular mechanism by which PfCRT confers quinoline antimalarial drug resistance entail the direct interaction of the drug molecule with the protein, but evidence for these theories is inferential. This thesis reports the labeling of PfCRT with a photoactivatable chloroquine analogue. The probe is shown to be specific and labeling is efficiently competed with other antimalarial drugs, suggesting a single drug binding site is present in the protein. The photolabeling site is mapped to within 11 amino acids, and a model is proposed in which PfCRT transmembrane helices 1, 9 and 10 form a drug binding pocket.
Download or read book Transport and Trafficking in the Malaria Infected Erythrocyte written by Gregory R. Bock and published by John Wiley & Sons. This book was released on 2008-04-30 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is an urgent need to uncover new therapies that will protect against malaria, as the parasite becomes increasingly resistant to available drugs and this book offers insights into three interrelated aspects of the malaria-infected erythrocyte: * The transport of solutes into and out of the infected cell and the use of specific trafficking pathways in drug targeting * The traffic of proteins produced by the intracellular parasite as an essential process for the biogenesis of transport systems. * The relationship between the transport of drugs into the infected cell and the mode of drug action and drug resistance.
Download or read book Membrane Transporters in Drug Discovery and Development written by Qing Yan and published by Methods in Molecular Biology. This book was released on 2010-04-26 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text provides practical methodologies of the ongoing research on membrane transporters, considering applications of transporter technologies in drug discovery and development.
Download or read book Saving Lives Buying Time written by Institute of Medicine and published by National Academies Press. This book was released on 2004-09-09 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: For more than 50 years, low-cost antimalarial drugs silently saved millions of lives and cured billions of debilitating infections. Today, however, these drugs no longer work against the deadliest form of malaria that exists throughout the world. Malaria deaths in sub-Saharan Africaâ€"currently just over one million per yearâ€"are rising because of increased resistance to the old, inexpensive drugs. Although effective new drugs called "artemisinins" are available, they are unaffordable for the majority of the affected population, even at a cost of one dollar per course. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance examines the history of malaria treatments, provides an overview of the current drug crisis, and offers recommendations on maximizing access to and effectiveness of antimalarial drugs. The book finds that most people in endemic countries will not have access to currently effective combination treatments, which should include an artemisinin, without financing from the global community. Without funding for effective treatment, malaria mortality could double over the next 10 to 20 years and transmission will intensify.
Download or read book Antimalarial Agents written by Graham L. Patrick and published by Elsevier. This book was released on 2020-05-30 with total page 624 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antimalarial Agents: Design and Mechanism of Action seeks to support medicinal chemists in their work toward antimalarial solutions, providing practical guidance on past and current developments and highlighting promising leads for the future. Malaria is a deadly disease which threatens half of the world’s population. Advances over several decades have seen vast improvements in the eff ectiveness of both preventative measures and treatments, but the rapid adaptability of the disease means that the ongoing search for improved and novel antimalarial drugs is essential. Beginning with a historical overview of malaria and antimalarial research, this book goes on to describe the biological aspects of malaria, highlighting the lifecycle of the parasite responsible for malaria, the problem of resistance, genetic mapping of the parasite’s genome, established drug targets, and potential drug targets for the future. This sets the scene for the following chapters which provide a detailed study of the medicinal chemistry of antimalarial agents, with a focus on the design of antimalarial drugs. Drawing on the knowledge of its experienced authors, and coupling historic research with current fi ndings to provide a full picture of both past and current milestones, Antimalarial Agents: Design and Mechanism of Action is a comprehensive yet accessible guide for all those involved in the design, development, and administration of antimalarial drugs, including student academic researchers, medicinal chemists, malaria researchers, and pharmaceutical scientists. Consolidates both past and current developments in the discovery and design of antimalarial drugs Presents content in a style that is both thorough and engaging, providing a supportive and guiding reference to students and researchers from interdisciplinary backgrounds Highlights drug targets currently considered to be the most promising for future therapies, and the classes of compounds that are currently being studied and perfected
Download or read book Transporters as Drug Targets written by Gerhard F. Ecker and published by John Wiley & Sons. This book was released on 2017-04-10 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: As opposed to other books on the topic, this volume is unique in also covering emerging transporter targets. Following a general introduction to the importance of targeting transporter proteins with drugs, the book systematically presents individual transporter classes and explains their pharmacology and physiology. The text covers all transporter families with known or suspected importance as drug targets, including neurotransmitter transporters, ABC transporters, glucose transporters and organic ion transporters. The final part discusses recent advances in structural studies of transport proteins, assay methods for transport activity, and the systems biology of transporters and their regulation. With its focus on drug development issues, this authoritative overview is required reading for researchers in industry and academia targeting transport proteins for the treatment of disease.
Download or read book Rodent Malaria written by R. Killick-Kendrick and published by Elsevier. This book was released on 2012-12-02 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rodent Malaria reviews significant findings concerning malaria parasites of rodents, including their taxonomy, zoogeography, and evolution, along with life cycles and morphology; genetics and biochemistry; and concomitant infections. This volume is organized into eight chapters and begins by sketching out the history of the discovery of rodent as well as aspects of parasitology, immunology, and chemotherapy. These concepts are investigated two decades following Ignace Vincke's major discovery and Meir Yoeli's successful establishment of the method of cyclical transmission of the parasite. The following chapters focus on the taxonomy and systematics of the subgenus Vinckeia, with reference to the concepts of species and subspecies of animals and the degree to which they apply to malaria parasites, in particular to those of rodents. The discussion then shifts to how the rodent malaria parasites provide a unique insight into the subcellular organization of Plasmodium species, the use of rodent malaria as an experimental model to study immunological responses, and infectious agents that interact with malaria parasites. The book concludes with a chapter on malaria chemotherapy, with emphasis on the value of rodent malaria in antimalarial drug screening and the use of antimalarial drugs as biological probes. This book will be of interest to protozoologists and physicians as well as those from other disciplines including biochemistry, immunology, pharmacology, cell biology, and genetics.
Download or read book Modulation of Human and Malarial Glucose Transporter Activity by Lipids and Small Molecules written by Thomas E. Kraft and published by . This book was released on 2016 with total page 143 pages. Available in PDF, EPUB and Kindle. Book excerpt: Glucose transport is a fundamentally important process for maintenance and regulation of cellular metabolism in all kingdoms of life. Despite their high importance, detailed examination of glucose transport proteins in humans and parasites through biochemical, biophysical and structural properties was greatly hampered by the inability to express, purify and reconstitute sufficient amounts of active transporters. This dissertation describes strategies that led to the first successful expression, purification, stabilization and functional reconstitution of active insulin-responsive GLUT4 transport protein. Furthermore, the work described herein establishes a requirement of anionic and conical lipids for full activity of the mammalian glucose transporters GLUT3 and GLUT4, thereby extending the field of known membrane protein-lipid interactions to the family of structurally and functionally related human solute carriers. Because of its crucial role in parasite survival, the malarial glucose transporter PfHT has been extensively validated as drug target for different parasitic life stages in vitro and in animal models. The emergence of parasites with resistance to even the most potent existing anti-malarial drugs has made paramount the development of novel drugs that target essential pathways for parasite survival. We identified PfHT as molecular target of the antimalarial activity of the clinically used HIV inhibitor lopinavir which had been shown previously to decrease parasite viability in vitro, in vivo, and in patients. In order to find novel PfHT inhibitors with increased potency and selectivity over human orthologs, a high-throughput assay was developed that uses fluorescence as direct readout of PfHT mediated glucose transport inhibition. Validation of this approach was demonstrated by our success in identifying several verified hits in a screen of the MMV malaria box compound library. Importantly, we identified a potent PfHT inhibitor with >10 fold higher selectivity for PfHT over its human orthologs. These findings have high potential for direct application in large-scale screens and new drug development. Taken together, this work provides a novel framework for ongoing efforts to directly target glucose transporters in the treatment of human disease.
Download or read book Assessment of Long Term Health Effects of Antimalarial Drugs When Used for Prophylaxis written by National Academies of Sciences, Engineering, and Medicine and published by National Academies Press. This book was released on 2020-04-24 with total page 427 pages. Available in PDF, EPUB and Kindle. Book excerpt: Among the many who serve in the United States Armed Forces and who are deployed to distant locations around the world, myriad health threats are encountered. In addition to those associated with the disruption of their home life and potential for combat, they may face distinctive disease threats that are specific to the locations to which they are deployed. U.S. forces have been deployed many times over the years to areas in which malaria is endemic, including in parts of Afghanistan and Iraq. Department of Defense (DoD) policy requires that antimalarial drugs be issued and regimens adhered to for deployments to malaria-endemic areas. Policies directing which should be used as first and as second-line agents have evolved over time based on new data regarding adverse events or precautions for specific underlying health conditions, areas of deployment, and other operational factors At the request of the Veterans Administration, Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis assesses the scientific evidence regarding the potential for long-term health effects resulting from the use of antimalarial drugs that were approved by FDA or used by U.S. service members for malaria prophylaxis, with a focus on mefloquine, tafenoquine, and other antimalarial drugs that have been used by DoD in the past 25 years. This report offers conclusions based on available evidence regarding associations of persistent or latent adverse events.
Download or read book Advances in Malaria Research written by Deepak Gaur and published by John Wiley & Sons. This book was released on 2016-12-27 with total page 611 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly reviews our current understanding of malarial biology Explores the subject with insights from post-genomic technologies Looks broadly at the disease, vectors of infection, and treatment and prevention strategies A timely publication with chapters written by global researchers leaders
Download or read book An Overview of Tropical Diseases written by Amidou Samie and published by BoD – Books on Demand. This book was released on 2015-12-02 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tropical diseases affect millions of people throughout the world and particularly in the developing countries. The millennium development goals had specifically targeted HIV/AIDS and Malaria for substantial reduction as well as Tuberculosis while many other tropical diseases have been neglected. The new sustainable development goals have not made such distinction and have targeted all diseases for elimination for the improvement of the quality of life of human beings on earth. The present book was developed to provide an update on issues relevant to the treatment of selected tropical diseases such as tuberculosis, malaria, leishmaniasis, schistosomiasis and ectoparasites such as chiggers which are widely distributed throughout the world. The control of these infections has been hampered by the development of drug resistance and the lack of the development of new and more effective drugs. The understanding of the biochemical processes underlying drug activity is therefore essential for the potential elimination of these infections.
