Hits and Lead Discovery in the Identification of New Drugs against the Trypanosomatidic Infections

This chapter focuses on the identification of new drugs for the treatment of trypanosomatidic infections such as Chagas disease, caused by T. cruzi, and Human African Trypanosomiasis (HAT), caused by T. brucei. Chagas disease, also referred to as American Trypanosomiasis, represents a serious medical and socioeconomic burden for over 21 countries of Latin America. The treatment of both the acute and chronic stages of Chagas disease is based on chemotherapy. Pentamidine is currently the first-line option for treating the initial stage of HAT. Melarsoprol, eflornithine and nifurtimox are the only drugs actually effective in the second stage of HAT. The chapter discusses ligand-based approaches for the development of new compounds on the basis of already known active compounds, natural compounds or marketed drugs. It describes the synthesis and structure-activity relationship studies of the most important compound classes with promising antitrypanosomal activity.