Download or read book Development of a Dynamic Receptor based Pharmacophore Model of Plasmodium Falciparum Spermidine Synthase for Selective Inhibitor Identification written by Pieter Buys Burger and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria affects the daily lives of more than 2 billion people worldwide and has been estimated to result in 300-500 million clinical cases annually leading to approximately 2 million deaths, mainly caused by the most virulent malaria species, Plasmodium falciparum. The lack of a vaccine and the rapid emergence and spread of drug resistant strains of P. falciparum, necessitate the development of new antimalarials and the identification and validation of new parasite-specific therapeutic targets. Numerous studies directed at interfering with the polyamine biosynthetic pathway in P. falciparum have shown its potential as a target for the development of a new class of antimalarials. The essential nature of P. falciparum spermidine synthase (PfSpdSyn), an enzyme in the polyamine pathway of the parasite warranted the further investigation to find novel lead compounds. The high cost and attrition rate of drug discovery has resulted in the implementation of smart drug discovery platforms in both academia and industry. The strategy implemented in this study involved the development of a dynamic receptor-based pharmacophore model (DPM) of PfSpdSyn complemented by a knowledge-based rational design strategy. The use of pharmacophore models to identify lead compounds has become increasingly popular over the last decade and has been shown to be a reliable method in the drug discovery process. The development of a DPM allows for the incorporation of protein exibility within the drug design process. This methodology results in a wealth of information of the chemical space of the active site and was incorporated in designing new inhibitors against PfSpdSyn using a knowledge-based rational design strategy. The active site of PfSpdSyn was subdivided into four binding regions (DPM1-DPM4) to allow for the identi cation of fragments binding within these speci c binding regions. DPMs representative of the chemical characteristics of each binding region were constructed and subsequently screened against the drug-like subset of the ZINC database. From the screens a total of nine compounds were selected for in vitro testing, complementing each other in exploring specific active site binding characteristics. From these compounds a new lead compound N-(3-aminopropyl)-cyclohexylamine (NAC: Ki 2.8 ; M) was identified for PfSpdSyn. NAC was specifically designed to bind in both the putrescine and decarboxylated adenosylmethionine cavities by chemically bridging the catalytic center and was confirmed by kinetic studies. NAC shows great potential for lead optimization to increase its binding affinity. This study then paves the way for lead optimization and possibly the development of a novel antimalarial. The development of a DPM for PfSpdSyn has seen the establishment of this methodology in the Bioinformatics and Computational Biology Unit, Department of Biochemistry at the University of Pretoria. It can be concluded that the development of a DPM complemented by a knowledge-based rational design strategy is an effective approach for the identification of novel lead compounds in the presence of a 3D target structure. This paves the way for more studies on both malaria and other drug targets using DPMs. Copyright.

Download or read book Computational Design of Chemicals for the Control of Mosquitoes and Their Diseases written by James Devillers and published by CRC Press. This book was released on 2017-12-15 with total page 479 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is a compelling need for new drugs and efficient treatments against mosquito-borne diseases. Environmentally safe, but effective insecticides that address the problems of resistance are required. Computational Design of Chemicals for the Control of Mosquitoes and Their Diseases explains how the search for new substances effective against mosquitoes and their diseases has benefited from the use of in silico techniques. QSAR modeling is suited to identify the key structural features and/or physicochemical properties explaining an activity and to propose candidate molecules for further evaluation by laboratory tests. Homology modeling is useful to approximate the 3D structure of proteins of interest. Pharmacophore modeling is a powerful means to capture the chemical features responsible for an activity and to identify new potentially active compounds via the virtual screening of databases. Fugacity modeling and a wealth of other modeling paradigms are useful for risk assessment in vector borne disease control.

Download or read book Pharmacophore Perception Development and Use in Drug Design written by Osman F. Güner and published by Internat'l University Line. This book was released on 2000 with total page 598 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the early 1900s, Paul Ehrlich first defined pharmacophores as molecule frameworks that carry the essential features responsible for a drug's biological activity, and the modern definition is little changed. The 27 studies here begin by tracing the evolution of the concept in pharmaceutical research, then cover analog-based and receptor-based varieties, new algorithms, and the future of research. Among the specific topics: pharmacophores based on multiple common-feature alignments; modeling programs including HypoGen, DISCO, Catalyst, HipHop, GASP, Chem-X, Apex-3D, CoMFA; pharmacophore-based molecular docking, a technique for developing a pharmacophore model that accommodates inherent protein flexibility; and the effect of variable weights and tolerances on predictive model generation. Books in Print lists only one other book on the topic of pharmacophores. Annotation copyrighted by Book News, Inc., Portland, OR

Download or read book Innovations and Implementations of Computer Aided Drug Discovery Strategies in Rational Drug Design written by Sanjeev Kumar Singh and published by Springer Nature. This book was released on 2021-02-02 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents various computer-aided drug discovery methods for the design and development of ligand and structure-based drug molecules. A wide variety of computational approaches are now being used in various stages of drug discovery and development, as well as in clinical studies. Yet, despite the rapid advances in computer software and hardware, combined with the exponential growth in the available biological information, there are many challenges that still need to be addressed, as this book shows. In turn, it shares valuable insights into receptor-ligand interactions in connection with various biological functions and human diseases. The book discusses a wide range of phylogenetic methods and highlights the applications of Molecular Dynamics Simulation in the drug discovery process. It also explores the application of quantum mechanics in order to provide better accuracy when calculating protein-ligand binding interactions and predicting binding affinities. In closing, the book provides illustrative descriptions of major challenges associated with computer-aided drug discovery for the development of therapeutic drugs. Given its scope, it offers a valuable asset for life sciences researchers, medicinal chemists and bioinformaticians looking for the latest information on computer-aided methodologies for drug development, together with their applications in drug discovery.

Download or read book Protein Ligand Interactions written by Holger Gohlke and published by John Wiley & Sons. This book was released on 2012-05-21 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: Innovative and forward-looking, this volume focuses on recent achievements in this rapidly progressing field and looks at future potential for development. The first part provides a basic understanding of the factors governing protein-ligand interactions, followed by a comparison of key experimental methods (calorimetry, surface plasmon resonance, NMR) used in generating interaction data. The second half of the book is devoted to insilico methods of modeling and predicting molecular recognition and binding, ranging from first principles-based to approximate ones. Here, as elsewhere in the book, emphasis is placed on novel approaches and recent improvements to established methods. The final part looks at unresolved challenges, and the strategies to address them. With the content relevant for all drug classes and therapeutic fields, this is an inspiring and often-consulted guide to the complexity of protein-ligand interaction modeling and analysis for both novices and experts.

Download or read book Mammalian Transient Receptor Potential TRP Cation Channels written by Bernd Nilius and published by Springer. This book was released on 2014-06-24 with total page 569 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​In this fast moving field the main goal of this volume is to provide up-to-date information on the molecular and functional properties and pharmacology of mammalian TRP channels. Leading experts in the field describe properties of a single TRP protein/channel or portray more general principles of TRP function and important pathological situations linked to mutations of TRP genes or their altered expression. Thereby this volume on Transient Receptor Potential (TRP) Channels provides valuable information for readers with different expectations and backgrounds, for those who are approaching this field of research as well as for those wanting to make a trip to TRPs.

Download or read book Handbook of Anticancer Drugs from Marine Origin written by Se-Kwon Kim and published by Springer. This book was released on 2014-11-27 with total page 801 pages. Available in PDF, EPUB and Kindle. Book excerpt: This timely desk reference focuses on marine-derived bioactive substances which have biological, medical and industrial applications. The medicinal value of these marine natural products are assessed and discussed. Their function as a new and important resource in novel, anticancer drug discovery research is also presented in international contributions from several research groups. For example, the potential role of Spongistatin, Apratoxin A, Eribulin mesylate, phlorotannins, fucoidan, as anticancer agents is explained. The mechanism of action of bioactive compounds present in marine algae, bacteria, fungus, sponges, seaweeds and other marine animals and plants are illustrated via several mechanisms. In addition, this handbook lists various compounds that are active candidates in chemoprevention and their target actions. The handbook also places into context the demand for anticancer nutraceuticals and their use as potential anti-cancer pharmaceuticals and medicines. This study of advanced and future types of natural compounds from marine sources is written to facilitate the understanding of Biotechnology and its application to marine natural product drug discovery research.

Download or read book Human Viruses Diseases Treatments and Vaccines written by Shamim I. Ahmad and published by Springer Nature. This book was released on 2021-05-19 with total page 745 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses current evidence on human viruses and provides an extensive coverage of newly emerged viruses and current strategies for treatment. Offering a new perspective in view of the re-emergence of Ebola in African countries and Dengue in India and Pakistan, the contents include chapters on emergence, pathogenicity, epidemiology and vaccine uptake. Human Viruses: Diseases, Treatments and Vaccines: The New Insights discusses a range of viruses from the most common such as Influenza and Hepatitis to Zika, Poliomyelitis and Chikungunya among many others. It is authored by a team of experts on viral disease and will be of immense use to virologists, public health experts and clinicians.

Download or read book Toxicoepigenetics written by Shaun D. McCullough and published by Academic Press. This book was released on 2018-11-02 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: Toxicoepigenetics: Core Principles and Applications examines the core aspects of epigenetics, including chromatin biology, DNA methylation, and non-coding RNA, as well as fundamental techniques and considerations for studying each of these mechanisms of epigenetic regulation. Although its integration into the field of toxicology is in its infancy, epigenetics have taken center stage in the study of diseases such as cancer, diabetes, and neurodegeneration. Increasing the presence of epigenetics in toxicological research allows for a more in-depth understanding of important aspects of toxicology such as the role of the environment and lifestyle influencing the individual susceptibility to these effects and the trans-generational transmission of these health effects and susceptibilities. Methods chapters are included to help improve efficacy and efficiency of protocols in both the laboratory and the classroom. Toxicoepigenetics: Core Principles and Applications is an essential book for researchers and academics using epigenetics in toxicology research and study. Introduces the fundamental principles and practices for understanding the role of the epigenome in toxicology Presents the foundation of epigenetics for toxicologists with a broad range of backgrounds Discusses the incorporation of epigenetics and epigenomics into current toxicological studies and interpretation of epigenetic data in toxicological applications

Download or read book Dynamic Combinatorial Chemistry written by Joost N. H. Reek and published by John Wiley & Sons. This book was released on 2010-02-02 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: This long-awaited first book on this exciting new field in organic and supramolecular chemistry explains the fundamentals as well as possible applications of DCC. Authored by the "Who's Who" of DCC it spans the whole range of topics: catalysts, sensors, polymers, ligands, receptors, concluding with a look at future developments and perspectives. All set to become the standard text in the field, this one-stop reference contains everything organic, catalytic, polymer, physical and biochemists need to know.

Download or read book Drug Targets in Kinetoplastid Parasites written by Hemanta K. Majumder and published by Springer. This book was released on 2011-01-24 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Evidence Based Validation of Traditional Medicines written by Subhash C. Mandal and published by Springer Nature. This book was released on 2021-01-18 with total page 1135 pages. Available in PDF, EPUB and Kindle. Book excerpt: The demand for traditional medicines, herbal health products, herbal pharmaceuticals, nutraceuticals, food supplements and herbal cosmetics etc. is increasing globally due to the growing recognition of these products as mainly non-toxic, having lesser side effects, better compatibility with physiological flora, and availability at affordable prices. In the last century, medical science has made incredible advances all over the globe. In spite of global reorganization and a very sound history of traditional uses, the promotion of traditional medicine faces a number of challenges around the globe, primarily in developed nations. Regulation and safety is the high concern for the promotion of traditional medicine. Quality issues and quality control, pharmacogivilane, scientific investigation and validation, intellectual property rights, and biopiracy are some key issues that restrain the advancement of traditional medicine around the globe. This book contains diverse and unique chapters, explaining in detail various subsections like phytomolecule, drug discovery and modern techniques, standardization and validation of traditional medicine, and medicinal plants, safety and regulatory issue of traditional medicine, pharmaceutical excipients from nature, plants for future. The contents of the book will be useful for the academicians, researchers and people working in the area of traditional medicine.

Download or read book Biocatalysis written by Qayyum Husain and published by Springer Nature. This book was released on 2019-09-03 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book introduces readers to industrially important enzymes and discusses in detail their structures and functions, as well as their manifold applications. Due to their selective biocatalytic capabilities, enzymes are used in a broad range of industries and processes. The book highlights selected enzymes and their applications in agriculture, food processing and discoloration, as well as their role in biomedicine. In turn, it discusses biochemical engineering strategies such as enzyme immobilization, metabolic engineering, and cross-linkage of enzyme aggregates, and critically weighs their pros and cons. Offering a wealth of information, and stimulating further research by presenting new concepts on enzymatic catalytic functions in basic and applied contexts, the book represents a valuable asset for researchers from academia and industry who are engaged in biochemical engineering, microbiology and biotechnology.

Download or read book Biotechnology and Production of Anti Cancer Compounds written by Sonia Malik and published by Springer. This book was released on 2017-04-21 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses cancers and the resurgence of public interest in plant-based and herbal drugs. It also describes ways of obtaining anti-cancer drugs from plants and improving their production using biotechnological techniques. It presents methods such as cell culture, shoot and root culture, hairy root culture, purification of plant raw materials, genetic engineering, optimization of culture conditions as well as metabolic engineering with examples of successes like taxol, shikonin, ingenol mebutate and podophylotoxin. In addition, it describes the applications and limitations of large-scale production of anti-cancer compounds using biotechnological means. Lastly, it discusses future economical and eco-friendly strategies for obtaining anti-cancer compounds using biotechnology.

Download or read book Encapsulation of Active Molecules and Their Delivery System written by Shirish Sonawane and published by Elsevier. This book was released on 2020-03-24 with total page 379 pages. Available in PDF, EPUB and Kindle. Book excerpt: Encapsulation of Active Molecules and Their Delivery System covers the key methods of preparation of encapsulation, as well as release mechanisms and their applications in food, biotechnology, metal protection, drug delivery, and micronutrients delivery in agriculture. The book also provides real-life examples of applications in food and other industries. Sections encompasses (i) Synthesis and characterization methods of micro- and nanocarriers as the delivery systems, (ii) Up-to-date encapsulation techniques in the areas of pharmaceuticals, nutraceuticals and corrosion, (iii) The release methods of the encapsulated materials, and (iv) Industry perspectives, including scale up of the processes. Focuses on encapsulation processes in chemical and materials engineering and biotechnology Provides a relevant resource for the pharmaceutical and food industries Presents wide coverage on the entrapment of molecules that scales-up to industrial sized needs

Download or read book Pharmacogenomics written by Julio Licinio and published by John Wiley & Sons. This book was released on 2009-07-30 with total page 599 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work represents the first comprehensive publication in the innovative field of pharmacogenomics, a field which is set to revolutionize pharmaceutical research. In addition to renowned editors, the list of contributors is a "who-is-who" in the field. Broad coverage of all aspects of pharmacogenomics with a full presentation of applications to disease conditions is featured. Anyone involved in pharmaceutical research and drug development needs this book to keep up with this new and revolutionary approach

Download or read book G Quadruplex Nucleic Acids written by Danzhou Yang and published by Humana. This book was released on 2020-09-07 with total page 437 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers the structures, properties, and functions of G-quadruplexes in a wide range of biological disciplines, including therapeutic intervention and biomaterial application. The chapters in this book explore a wide range of vital and new experimental techniques used in the study of G-quadruplexes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, G-Quadruplex DNA: Methods and Protocols is a valuable resource for both novice and experienced researchers who work in biophysics, structural biology, computational biology, biochemistry, and molecular and cell biology, and who want to learn more about the potential roles and effects of G-quadruplex in these fields.