Preface

Neglected tropical diseases are a conjunct of infectious diseases that affect several countries around the world, mainly those with tropical and subtropical conditions, affecting the population living in poverty and without basic sanitation, causing severe damage to the health of the population and economy of the countries. They are considered “neglected” due to the low investment of pharmaceutical companies in P&D for new drugs against these diseases. Thus, despite alarming statistics, there are few drugs to treat these conditions, with scientific research institutions being the main ones for developing new agents against these conditions [1-4].

In view of this, the book “Advances in the Medicinal Chemistry of Neglected Tropical Disease and Related Infectious Diseases” appears, highlighting the main developments in recent years against this disease, mainly in innovative compounds and molecular targets that can be explored in subsequent drug design studies.

This first edition is organized into ten chapters, namely:

Chapter 1 “Medicinal Chemistry of Neglected Tropical Diseases (NTDs): From Targets to Drugs,” briefly introduces these diseases and some actual drug targets explored in the drug design process. The authors provide great material focusing on epidemiological, clinical manifestations, and current treatments. In addition, the structure, functions, and the most promising inhibitors of the N-myristoyltransferase, nitroreductases, topoisomerases, pyrimidine synthesis pathway, and mitochondrial alterations are shown and provide its importance in the drug design and development process. Finally, this chapter can guide research worldwide to discover a promising drug against several NTDs.

Chapter 2 “Advancements in Antileishmanial Drug Discovery: Targeting Druggable Pathways and Overcoming Treatment Challenges” explores the latest developments in synthetic, semi-synthetic, and natural compounds identified in in silico, in vitro, and in vivo assays against leishmaniasis and a brief introduction about some new targets used in the design process. In addition, the authors provide information about the primary chemical scaffolds explored against leishmaniasis, such as flavonoids and chalcones, naphthoquinones and iridoids, saponins, quinolines, lignans, terpenes and terpenoids, and others synthetic nucleus. Finally, the drug target of each scaffold is proposed, and this information can be used in the drug design of further compounds.

Chapter 3 “Chagas Diseases: State Of the Art and New Perspectives,” provides new information about Chagas diseases, including the physiopathology and the drugs used in the clinical treatment. In addition, the authors provide new insights into the drug design and discovery process, highlighting the main explored drug targets, the chemical scaffolds used, and novel promising drugs in clinical practice.

Chapter 4 “Novel Agents against Human African Trypanosomiasis: Updates on Medicinal Chemistry and Target Identification,” highlights the clinical manifestations and current treatments against Trypanosoma brucei, an etiological agent of the sleeping sickness, or human African trypanosomiasis. Furthermore, the most prominent drug targets are shown, such as protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs), heat shock proteins (HSPs), kinetoplastid proteasome, Tb Cathepsin L (TbCatL), Tb UDP-Glucose 4’-Epimerase (TbGalE), and others that provide new insights in drug design to researchers worldwide.

Chapter 5 “Schistosomiasis: State Of the Art and New Perspectives” similar to the previous chapters, provides information about the life cycle of the schistosome and other parameters such as clinical manifestations and the current drug treatment. In addition, some repurposed drugs are explored as having promising potential against this disease, and the main research focuses on new drug targets, highlighting HDAC and Sirtuin inhibitors, histone methylation, protein kinases, protease, CYP450, transporters inhibitors, and others that can be a promising intervention in the drug design of antischistosomal drugs.

Chapter 6 “Progress In Medicinal Chemistry For Neglected Tropical Diseases: A Focus On DENV Drug Discovery (2014 - 2023),” explores the potential of classical drug targets of dengue virus and highlights the main features to design anti-dengue drugs. Similar to the chapters above, the functions of some non-structural targets, such as protease, RdRp, methyltransferase, and structural targets, such as E protein and others, were characterized. Thus, this chapter provides critical information for designing innovative anti-dengue compounds.

Chapter 7, “Malaria: State Of the Art and New Perspectives,” discusses the actual drug treatment and its difficulties due to the parasite's resistance and the urgency to discover new drugs to overcome this. For this, it is necessary to explore new targets, as shown in the manuscript, such as channels/transporters, aquaporin channel, Plasmodial surface anion channel, hexose transporter, choline transporter, apicoplast, cyclin-dependent protein kinases (CDKs), nucleic acid metabolism, mitochondrial system, redox system, shikimate pathway, isoprenoid biosynthesis, parasite proteases, membrane biosynthesis, and pfTBP–pfTFIIB interface. Finally, the authors highlight the main chemical scaffolds explored that can provide an innovative drug against this disease.

Chapter 8 “On The Trail of Zika Virus: Understanding its Druggable Targets,” explores the structural and non-structural proteins used in the drug design against the Zika virus. Thus, the authors provide critical information about the structure, functions, and main inhibitors of the NS1, NS2A, NS2B, NS3, NS2B/NS3, NS4B, NS5, envelop (E) protein, prM, capsid (C) protein, and some alternatives pathways that can be promising to discover an innovative anti-Zika drug.

Chapter 9 “Mycobacterium tuberculosis: Recent Advances in Drug Discovery and Targets – A SAR-Based Approach,” explores the epidemiology and insights into drug design and development against tuberculosis. Thus, the authors highlight the importance of identifying new targets to provide an innovative drug and overcome the parasite's resistance to the actual clinical drugs of this disease. For this, targets such as DNA gyrase, shikimate pathway, adenosine kinases, and others are shown, highlighting their structure and functions. In addition, the authors provide exceptional work on the structure-activity relationship (SAR) to provide critical information on the structural features of the most actual discovered inhibitors.

Chapter 10 “Drug discovery in Fasciola hepatica: Few Steps in the Last Ten Years,” highlights the urgency to discover new flukicide drugs and explores the drug design and discovery against Fasciola hepatica. For this, the authors provide excellent material about the explored drug targets, such as cathepsin Ls, triosephosphate isomerase, thioredoxin glutathione reductase, and other biological structures of the fasciola that do not have an experimental inhibitor, as well as the inhibitors identified in phenotypic drug screenings, and the function of the drug repurposing to discover drugs against fasciola. This chapter can provide new horizons for the readers and critical information to use in drug design against these diseases.

We hope our book will serve as a guide for researchers worldwide and help discover drugs against these diseases, ending these threatening agents.