Polyamine and Trypanothione Pathways as Targets for Novel Antileishmanial Drugs

Abstract

Leishmaniasis is an infectious disease classified by WHO as one of the neglected tropical diseases. Due to the lack of human vaccines, chemotherapeutic agents represent the only strategy for disease combat. However, the current treatment is marked by variable efficacy, high toxicity, and high cost. Thus, the search for more efficient antileishmanial agents becomes urgent. Several studies carrying out the discovery or development of potent inhibitors of key enzymes of Leishmania metabolism have demonstrated promising results. The polyamine and trypanothione pathways are essential for parasite survival and pathogenesis. Polyamine synthesis allows parasite growth and influences infectivity. Moreover, the final product of the polyamine pathway spermidine is required for the synthesis of trypanothione, a scavenger of reactive oxygen and nitrogen species, which is essential for the maintenance of Leishmania redox balance. In the present chapter, the advances in the use of synthetic and natural inhibitors of the polyamine and trypanothione pathways from Leishmania are discussed.