Targets for Anti-T. cruzi Drugs in the Post-Genomic Era

Alicia      Merlino; Mercedes      Gonzalez; Hugo      Cerecetto

Abstract

The information of the complete genome sequences of Trypanosoma cruzi revealed that its genome contains nearly to 10,000 protein-coding genes. This vast amount of new information allows the identification of therapeutic targets in an accurate and undoubtedly forms. The current post-genomic period is a special moment in the anti-T. cruzi drug discovery and development ushering this moment as the anti-Chagas drug discovery era. In this review we describe, from a medicinal chemistry point of view, several identified potential biological targets for drugs development. We discuss the validity and druggability as anti-Chagas objectives of prenyl converting and transferring enzymes, cAMP-specific phosphodiesterases, polyamine and trypanothione synthetic pathways, triosephosphate isomerase, α-hydroxyacid dehydrogenases and trans-sialidase.

Keywords: Chagas' disease, enzymatic inhibitors, drugs development, Trypanosoma cruzi, ergosterol biosynthetic pathway, trypanothione reductase, farnesyltransferase inhibitors, cAMP-specific phosphodiesterases, Dipyridamole, sulfinyl radicals, glutathionylated products