Approaches for the development of new anti-Trypanosoma cruzi agents.

The recent highlights on the biochemical pathways of Trypanosoma cruzi have allowed a significant improvement in the development of new strategies for drug design and also in the understanding of the mechanisms of action of new trypanocidal agents. Several biochemical pathways of fundamental importance and validated targets (e.g. cysteine protease cruzain, trypanothione reductase, trans-sialidase) of T. cruzi have proved usefulness for drug development in many examples of new candidates to anti-T. cruzi drugs. This review will focus on some approaches used for the design of new potential trypanocidal agents, exploring modern concepts of medicinal chemistry such as bioisosterism, molecular hybridization, bioinspired design in lead compounds, as well as the complexation of transition metals with bioactive ligands. The examples discussed in this article may serve as lessons for the antitrypanosomal drug design.