The Pursuit of Novel Anti-leishmanial Agents by High-throughput Screening (HTS) of Chemical Libraries

Abstract

In this chapter we review screening methodologies and concepts that have been applied to discover new anti-leishmanial compounds within large chemical libraries. There is a consensus regarding the need for more efficacious, safer and inexpensive oral drugs for the treatment of leishmaniasis. For the sake of unprecedented novelty, the pursuit of new chemical entities (NCEs) starts with the screening of molecules of unknown activity. High-throughput screening (HTS) has become the classical approach to interrogate large chemical libraries (i.e. from hundreds of thousands to a few millions compounds) in a time- and cost-effective manner. HTS against Leishmania has meant a challenge to develop and implement the right assays and selection tactics. Biosafety, life-cycle stage of the parasite (i.e. promastigotes vs. amastigotes), culture conditions (i.e. axenic vs. intracellular) and source of host cells (i.e. immortalized cells vs. primary macrophages) have been some of the issues addressed in order to make compatible both biological relevance and do-ability. Herewith we walk the reader through different solutions adopted and implemented by the scientific community in the field.