Strategies in the drug discovery and development for leishmaniasis: immunomodulators, natural products, synthetic compounds, and drug repositioning

Strategies in the drug discovery and development for leishmaniasis: immunomodulators, natural products, synthetic compounds, and drug repositioning
Author: Taís Fontoura de Almeida
Publisher: Frontiers Media SA
Total Pages: 133
Release: 2024-05-15
Genre: Science
ISBN: 2832548997

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Leishmaniases are a group of tropical diseases that affect millions of people worldwide. They are considered neglected diseases prevalent in emerging countries in Latin America, West Africa, and Southeast Asia and still occurring in Mediterranean countries. There is no human vaccine available to prevent and control the disease infection. For the last 70 years, the available chemotherapy has been constituted by first-line (pentavalent antimonials) and second-line drugs (amphotericin B, pentamidine, paramomycin, and miltefosine). Its route of administration is difficult, the treatment is long, and its efficiency varies depending on the parasite species and clinical manifestations, which results in the emergence of resistant cases. Moreover, they present high toxicity to patients, and even some less toxic formulations available, are still expensive for the poorest countries’ vulnerable populations. This often leads to abandonment and failure of treatment. The medical-scientific community is facing difficulties to overcome these issues with new suitable therapies, and the identification of new drug targets. So, it means that efforts to identify new strategies must continue.

Drug Repurposing

Drug Repurposing
Author: Mithun Rudrapal
Publisher: BoD – Books on Demand
Total Pages: 225
Release: 2023-06-07
Genre: Medical
ISBN: 1837687765

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Drug repurposing (or drug repositioning) is defined as the process of identifying new pharmacological indications of old, existing, investigational, or FDA-approved drugs for use in the treatment of diseases other than the drugs’ original intended therapeutic use. Drug Repurposing - Advances, Scopes and Opportunities in Drug Discovery delivers up-to-date information on the identification of newer uses, molecular mechanisms, and novel targets of existing drug candidates through the application of various experimental, biophysical, and computational approaches and techniques. Chapters discuss recent advances in drug repurposing strategies that are currently being used in the discovery and development of drugs against difficult-to-treat, rare, and life-threatening diseases, including microbial infections, COVID-19, parasitic diseases, cardiovascular diseases, neurological disorders, and cancer. The book also discusses the modern experimental assays (HTS) and computational techniques including informatics and databases, molecular docking and dynamics, artificial intelligence and machine learning, virtual screening and pharmacophore modeling, proteomics and metabolomics, and network pharmacology and systems biology approaches. Some of the key features of the book are: • Presents the strategies available for the development of drugs by drug repurposing approaches through various experimental and computational techniques for the treatment of difficult-to-treat, rare, and deadly diseases • Summarizes the latest advances in the application of drug repurposing strategies, techniques, and approaches in the discovery and development of drugs • Depicts drug development approaches from existing drug candidates and/or lead molecules through modern experimental assays, biophysical tools, and computational techniques Written by a global team of experts, this book is useful for drug discovery scientists, drug developers, medicinal chemists, phytochemists, pharmacologists, clinicians, biochemists, biomedical scientists, healthcare professionals, researchers, teaching faculty, and students.

Drug Discovery for Leishmaniasis

Drug Discovery for Leishmaniasis
Author: Luis Rivas
Publisher: Royal Society of Chemistry
Total Pages: 422
Release: 2017-10-26
Genre: Science
ISBN: 1788012585

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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.

Drug Discovery from Nature

Drug Discovery from Nature
Author: S. Grabley
Publisher: Springer Science & Business Media
Total Pages: 380
Release: 1998-11-26
Genre: Medical
ISBN: 9783540648444

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This book is unique in covering the present status and future potential of natural products in drug discovery. It provides readers with recent information regarding the impact on drug discovery, development and strategies, technical and automation aspects, and methods based on biochemistry as well as molecular biology, highlighting compounds from natural sources. Special emphasis is placed on the various strategies to gain access to natural compounds and combinatorial approaches by making use of both synthetic and biological methods.

Drug Discovery in Africa

Drug Discovery in Africa
Author: Kelly Chibale
Publisher: Springer Science & Business Media
Total Pages: 453
Release: 2012-08-09
Genre: Science
ISBN: 3642281753

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Drug discovery originating in Africa has the potential to provide significantly improved treatment of endemic diseases such as malaria, tuberculosis and HIV/AIDS. This book critically reviews the current status of drug discovery research and development in Africa, for diseases that are a major threat to the health of people living in Africa. Compiled by leading African and international experts, this book presents the science and strategies of modern drug discovery. It explores how the use of natural products and traditional medicines can benefit from conventional drug discovery approaches, and proposes solutions to current technological, infrastructural, human resources, and economic challenges, which are presented when attempting to engage in full-scale drug discovery. Topics addressed are varied; from African medicinal plants to marine bioprospecting, pharmacogenetics and the use of nanotechnology. This book brings together for the first time a collection of strategies and techniques that need to be considered when developing drugs in an African setting. It is an unprecedented and truly international effort, highlighting the remarkable effort made so far in the area of drug discovery research by African scientists, and scientists from other parts of the world working on African health problems.

Natural Products

Natural Products
Author: Lixin Zhang
Publisher: Springer Science & Business Media
Total Pages: 380
Release: 2007-11-17
Genre: Medical
ISBN: 1592599761

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A fresh examination of the past successes of natural products as medicines and their new future from both conventional and new technologies. High-performance liquid chromatography profiling, combinatorial synthesis, genomics, proteomics, DNA shuffling, bioinformatics, and genetic manipulation all now make it possible to rapidly evaluate the activities of extracts as well as purified components derived from microbes, plants, and marine organisms. The authors apply these methods to new natural product drug discoveries, to microbial diversity, to specific groups of products (Chinese herbal drugs, antitumor drugs from microbes and plants, terpenoids, and arsenic compounds), and to specific sources (the sea, rainforest, and endophytes). These new opportunities show how research and development trends in the pharmaceutical industry can advance to include both synthetic compounds and natural products, and how this paradigm shift can be more productive and efficacious.

Studies in Natural Products Chemistry

Studies in Natural Products Chemistry
Author: Jens Rohloff
Publisher: Elsevier Inc. Chapters
Total Pages: 41
Release: 2013-03-15
Genre: Science
ISBN: 012808491X

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Leishmaniasis is a vector-borne parasitic disease caused by protozoan parasites belonging to the family Trypanosomatidae and genus Leishmania. The disease prevails in 88 subtropical and tropical countries in five continents where about 350 million people live. Approximately two million incidences of new cases are recorded every year, causing high morbidity and mortality with a wide spectrum of clinical manifestations in humans. Treatment for leishmaniasis depends on pentavalent antimonials developed 50 years ago as first-line drugs, whereas a limited range of other drugs such as paromomycin, miltefosine, and amphotericin B exist to supplement them. However, potential toxicity, costs, and emergence of drug-resistant pathogens are the most serious obstacles for successful treatment of the disease in most endemic areas. This demands the development of new antileishmanial agents. In this regard, the search for new drugs from various synthetic products continues, and involves also compounds isolated from natural sources and drugs used for the treatment of other ailments (cancer, viral infections, TB, immunosuppression, etc.) in order to discover compounds with unknown chemical structures and with potential novel modes of action. Medicinal and aromatic plants are a major source of natural organic compounds which are widely used as medicine. The extensive ethnomedicinal knowledge, diversity of plant species, and the disease burden worldwide necessitates the status of natural products in treatments of leishmaniasis to be assessed. This chapter will review plant crude extracts and fractions/active principles obtained from medicinal plants which are used in or have potential for the treatment of leishmaniasis. Plant species are systematically presented by family, bioactive phytochemicals in various classes, and results obtained on specific organisms tested. Recent empirical and rationale approaches for antileishmanial drug targeting and development of novel drugs derived from natural products will be discussed.

Discovery and Development of Therapeutics from Natural Products Against Neglected Tropical Diseases

Discovery and Development of Therapeutics from Natural Products Against Neglected Tropical Diseases
Author: Goutam Brahmachari
Publisher: Elsevier
Total Pages: 458
Release: 2019-04-15
Genre: Medical
ISBN: 0128157240

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Discovery and Development of Therapeutics from Natural Products against Neglected Tropical Diseases draws together research on medicinal agents from natural sources as starting points for the design of drugs against Neglected Tropical Diseases (NTDs). From the prediction of promising leads and identification of active agents, to the extraction of complex molecules, the book explores novel, economical and efficacious therapeutics for these diseases. It describes current research and the role of natural products, antimalarial compounds from marine natural products and sesquiterpene lactones, natural antileprotic agents, natural products with potential against Leishmaniasis, Trypanosomiasis and Dengue, and more. In addition, Quinoline and Isoquinoline alkaloids for developing new antiprotozoal agents are discussed, alongside anti-trypanosomatid heterocyclic compounds as structures for development. Combining the expertise of specialists from around the world, this volume aims to support and encourage researchers in the investigation of natural sources as starting points for the development of novel, safe and effective agents for use against neglected tropical diseases. Includes chapters written by active researchers and leading global experts deeply engaged in the research field of natural product chemistry for drug discovery Draws together cutting-edge research advances in natural product chemistry that are targeted at neglected tropical diseases Highlights the future potential of natural products as sources of novel medicinal compounds against neglected tropical diseases

Drug Discovery from Nature

Drug Discovery from Nature
Author: S. Grabley
Publisher: Springer
Total Pages: 0
Release: 2000
Genre: Medical
ISBN: 9783642602504

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This book is unique in covering the present status and future potential of natural products in drug discovery. It provides readers with recent information regarding the impact on drug discovery, development and strategies, technical and automation aspects, and methods based on biochemistry as well as molecular biology, highlighting compounds from natural sources. Special emphasis is placed on the various strategies to gain access to natural compounds and combinatorial approaches by making use of both synthetic and biological methods.