Molecular Advancements in Tropical Diseases Drug Discovery

Molecular Advancements in Tropical Diseases Drug Discovery presents in-depth knowledge relating to the detection of infection, epidemiology, drugs against various tropical diseases, new target sites for drug discovery and multidrug resistance issues using bioinformatics tools and approaches. The book's chapters are written by experts in their respective fields so that each disease is covered in a rational manner and with a solid foundation on existing facts and prospective research ideas. Updates knowledge about tropical diseases with recent advancements in the field Presents an overview of new research covering detection, infection, epidemiology and risk factors of the most common tropical diseases using bioinformatics tools Encompasses a detailed description of developments in drug discovery, new drugs and their molecular mechanisms of action

Molecular Advancements in Tropical Diseases Drug Discovery presents in-depth knowledge relating to the detection of infection, epidemiology, drugs against various tropical diseases, new target sites for drug discovery and multidrug resistance issues using bioinformatics tools and approaches. The book's chapters are written by experts in their respective fields so that each disease is covered in a rational manner and with a solid foundation on existing facts and prospective research ideas.

Medicinal Chemistry of Neglected and Tropical Diseases: Advances in the Design and Synthesis of Antimicrobial Agents consolidates and describes modern drug discovery and development approaches currently employed to identify effective chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTDs) from a medicinal chemistry perspective. Chapters are designed to cater to the needs of medicinal chemists who work with chemotherapeutic developments for NTDs, as well as serve as a guide to budding medicinal chemists who wish to work in this area. It will introduce rational drug design approaches adopted in designing chemotherapeutics and validated targets available for the purpose.

Rare diseases collectively affect millions of Americans of all ages, but developing drugs and medical devices to prevent, diagnose, and treat these conditions is challenging. The Institute of Medicine (IOM) recommends implementing an integrated national strategy to promote rare diseases research and product development.

WHO's Global Tuberculosis Report provides a comprehensive and up-to-date assessment of the TB epidemic and of progress in care and prevention at global, regional and country levels. This is done in the context of recommended global TB strategies and associated targets, and broader development goals. For the period 2016-2035, these are WHO's End TB Strategy and the United Nations' (UN) Sustainable Development Goals (SDGs), which share a common aim: to end the global TB epidemic. The main data sources for the report are annual rounds of global TB data collection implemented by WHO's Global TB Program since 1995 and databases maintained by other WHO departments, UNAIDS and the World Bank. In WHO's 2017 round of global TB data collection, 201 countries and territories that account for over 99% of the world's population and TB cases reported data.

Advances in Cell and Molecular Diagnostics brings the scientific advances in the translation and validation of cellular and molecular discoveries in medicine into the clinical diagnostic setting. It enumerates the description and application of technological advances in the field of cellular and molecular diagnostic medicine, providing an overview of specialized fields, such as biomarker, genetic marker, screening, DNA-profiling, NGS, cytogenetics, transcriptome, cancer biomarkers, prostate specific antigen, and biomarker toxicologies. In addition, it presents novel discoveries and clinical pathologic correlations, including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, and the description or polymorphisms linked to disease states. This book is a valuable resource for oncologists, practitioners and several members of the biomedical field who are interested in understanding how to apply cutting-edge technologies into diagnostics and healthcare. Encompasses the current scientific advances in the translation and validation of cellular and molecular discoveries into the clinical diagnostic setting Explains the application of cellular and molecular diagnostics methodologies in clinical trials Focuses on translating preclinical tests to the bedside in order to help readers apply the most recent technologies to healthcare

Following significant advances in deep learning and related areas interest in artificial intelligence (AI) has rapidly grown. In particular, the application of AI in drug discovery provides an opportunity to tackle challenges that previously have been difficult to solve, such as predicting properties, designing molecules and optimising synthetic routes. Artificial Intelligence in Drug Discovery aims to introduce the reader to AI and machine learning tools and techniques, and to outline specific challenges including designing new molecular structures, synthesis planning and simulation. Providing a wealth of information from leading experts in the field this book is ideal for students, postgraduates and established researchers in both industry and academia.

*Chapter 1: Neglected tropical disease, Chagas disease and target repurposing approach* The term "Neglected Tropical Diseases" (NTDs) most commonly refers to a group of parasitic and bacterial infectious disease affecting more than one billion people globally. There are 13 core diseases in the NTD group that are widespread across the countries from sub-Saharan Africa, Asia and to Latin America. These diseases primarily occur in rural areas, urban slums or conflict zones and affect 2.7 billion people who live on less than $2 per day, causing considerable morbidity and mortality. NTDs cause severe impact on physical and cognitive development, long-term illness, impaired childhood growth and development, adverse outcomes of pregnancy and trap the poor population in a cycle of poverty and disease. Many of these diseases are neglected at the global and local level by the government and private sector owing to the poor return of drug discovery research costs. Also, the emerging resistance to the current therapies can add more burdens to the poor nations The focus of this thesis is upon finding new leads for targeting protozoan parasite "Trypanosoma cruzi", responsible for Chagas disease (CD) by using Target repurposing approach. CD affects nearly 8 million people in Latin America and increasing number of cases reported across Europe and United States. Only two FDA approved drugs are currently available for treating CD. Target repurposing approach is a viable strategy to reduce the time and expense of discovering new therapeutic molecules. In this approach a molecular target in the parasites are matched with homologous human targets that has been previously pursued for drug discovery. We can utilize this knowledge of "druggable" targets in one organism to pursue new potential drug targets in the parasites. *Chapters 2 & 3: Scaffold replacements and head group truncation using in silico models* Our lab has applied target repurposing approach to identify several novel leads against protozoan parasites responsible for causing CD, human African sleeping sickness, leishmaniasis and malaria. Kinases are an extensively pursued class of drug targets to treat several diseases like cancer, immunological and neurological disorders, inflammation and infectious diseases. Lapatinib, an FDA approved dual tyrosine kinase inhibitor (EGFR/HER2) drug for treating breast cancer was repurposed for its anti-trypanosomal properties. Extensive SAR studies of lapatinib analogs led to sub-micromolar potent compound 1.25 (Figure 1.9) against the parasite "T. brucei". Hypothesizing that other parasites express similar kinase pathways, these libraries of compound were screened against other related parasites, which resulted in several lead compounds of micromolar potency. Encouraged by these results, we advanced our work to a scaffold replacement strategy. This resulted in the discovery of a potent lead 2.25b (Figure 2.6) with 0.09 μM activity against "T. cruzi". Despite having a good efficacy, the lead compound failed in the in vivo animal studies due to poor physicochemical properties. In an attempt to improve the physicochemical properties, we adopted a head group replacement strategy for the lead compound based on molecular modelling and virtual screening tools. The concept of ligand efficiency (LE) and lipophilic ligand efficiency (LLE/LiPE) were introduced with an aim to identify new leads. Finally, an attempt was made to establish a possible structure activity relationship (SAR) from the screening data of all the library series. *Chapter 4: Future directions* Final chapter summarizes the results of this thesis and provides the futuristic plan for the advancement of the current work to identify potent leads for Chagas disease.

Phytochemicals as Lead Compounds for New Drug Discovery presents complete coverage of the recent advances in the discovery of phytochemicals from medicinal plants as models to the development of new drugs and chemical entities. Functional bioactive compounds of plant origin have been an invaluable source for many human therapeutic drugs and have played a major role in the treatment of diseases around the world. These compounds possess enormous structural and chemical diversity and have led to many important discoveries. This book presents fundament concepts and factors affecting the choice for plant-based products, as well as recent advances in computer-aided drug discovery and FDA drug candidacy acceptance criteria. It also details the various bioactive lead compounds and molecular targets for a range of life-threatening diseases including cancer, diabetes, and neurodegenerative diseases. Written by a global team of experts, Phytochemicals as Lead Compounds for New Drug Discovery is an ideal resource for drug developers, phytochemists, plant biochemists, food and medicinal chemists, nutritionists and toxicologists, chemical ecologists, taxonomists, analytical chemists, and other researchers in those fields. It will also be very valuable to professors, students, and researchers in this domain. Presents fundamental concepts and factors affecting choice for plant-based products Details the FDA drug candidacy acceptance criteria, including bottlenecks and way forward Highlights recent advances in computational-based drug discovery Focuses on the discovery of new drugs and potential druggable targets for the treatment of chronic diseases of world importance

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.

Basic Principles of Drug Discovery and Development presents the multifaceted process of identifying a new drug in the modern era, which requires a multidisciplinary team approach with input from medicinal chemists, biologists, pharmacologists, drug metabolism experts, toxicologists, clinicians, and a host of experts from numerous additional fields. Enabling technologies such as high throughput screening, structure-based drug design, molecular modeling, pharmaceutical profiling, and translational medicine are critical to the successful development of marketable therapeutics. Given the wide range of disciplines and techniques that are required for cutting edge drug discovery and development, a scientist must master their own fields as well as have a fundamental understanding of their collaborator’s fields. This book bridges the knowledge gaps that invariably lead to communication issues in a new scientist’s early career, providing a fundamental understanding of the various techniques and disciplines required for the multifaceted endeavor of drug research and development. It provides students, new industrial scientists, and academics with a basic understanding of the drug discovery and development process. The fully updated text provides an excellent overview of the process and includes chapters on important drug targets by class, in vitro screening methods, medicinal chemistry strategies in drug design, principles of in vivo pharmacokinetics and pharmacodynamics, animal models of disease states, clinical trial basics, and selected business aspects of the drug discovery process. Provides a clear explanation of how the pharmaceutical industry works, as well as the complete drug discovery and development process, from obtaining a lead, to testing the bioactivity, to producing the drug, and protecting the intellectual property Includes a new chapter on the discovery and development of biologics (antibodies proteins, antibody/receptor complexes, antibody drug conjugates), a growing and important area of the pharmaceutical industry landscape Features a new section on formulations, including a discussion of IV formulations suitable for human clinical trials, as well as the application of nanotechnology and the use of transdermal patch technology for drug delivery Updated chapter with new case studies includes additional modern examples of drug discovery through high through-put screening, fragment-based drug design, and computational chemistry

Design of Hybrid Molecules for Drug Development reviews the principles, advantages, and limitations involved with designing these groundbreaking compounds. Beginning with an introduction to hybrid molecule design and background as to their need, the book goes on to explore a range of important hybrids, with hybrids containing natural products, molecules containing NO- and H2S-donors, dual-acting compounds acting as receptor ligands and enzyme inhibitors, and the design of photoresponsive drugs all discussed. Drawing on practical case studies, the hybridization of molecules for development as treatments for a number of key diseases is then outlined, including the design of hybrids for Alzheimer's, cancer, and malaria. With its cutting-edge reviews of breaking developments in this exciting field, the book offers a novel approach for all those working in the design, development, and administration of drugs for a range of debilitating disorders. Highlights an approach unimpaired by the limitations of the classical search for lead structures - one of the core problems in modern drug development processes, making the content of high relevance for both academic and non-academic drug development processes Pulls together research and design techniques in a novel way to give researchers the best possible platform from which to review the approaches and techniques applied Compares the advantages and disadvantages of these compounds Includes the very latest developments, such as photoactivatable and photo-responsive drugs

This book is for readers with some background in science, concerning the search for drugs, starting from molecular diversity in nature or molecular wilderness. Drug molecules may be used as such, or as starting points for improved drugs obtained from the interface of chemistry and biology. In some cases, the essential molecular features for drug properties from natural molecules may be identified and modified to more effective ones. In other cases, nature provides the targets, such as essential enzymes from infectious microorganisms, from which synthetic drugs can be designed. The mechanisms of action of drugs can be discerned by studying target–drug interactions. Nature may fight back, as in cases when microorganisms become resistant to drugs, but we can again use the chemistry–biology interface to obtain drugs which overcome the resistance. The battle goes on, hopefully with victory for both humans and balance of nature. This book differs from those available on the subject of natural products and drugs derived therefrom in that it looks at the broad picture on how materials and organisms from nature affect our health and how we have combined our knowledge in chemistry, biology, and biodiversity to promote our wellness from resources in the "molecular wilderness," with caveats on sustainable utilization of these resources. It is therefore suitable, not only for readers interested in science and medicine, but also for those with interest in policy issues concerning sustainable development, environment, and issues concerning interaction of science and society in general.