Drug Discovery Strategies for the Generation of Multitarget Ligands against Neglected Tropical Diseases

This chapter by choosing the field of neglected tropical diseases (NTDs) as the background therapeutic area describes efforts to develop multitarget drugs for solving the vexing medical problem. Among the various NTDs, the chapter focuses on three diseases most significant in terms of morbidity and mortality: human African trypanosomiasis (HAT), Chagas' disease, and leishmaniasis. A numerous class of hybrid anti‐trypanosomatid molecules is represented by the so‐called targeted drugs, which combine a framework with antiparasitic activity with a fragment recognized by a parasite transporter. A multitarget‐directed ligand (MTDL) is a single chemical entity that simultaneously recognizes different targets inside the parasite. The chapter then presents the report on the different approaches that are exploited to obtain innovative hybrid small molecules. Modern drug discovery for NTDs is carried out using both target‐based and phenotypic approaches. The target‐based approaches to NTDs are a widely used route for drug discovery programs aimed at identifying new lead compounds for diseases.