Approaches for the Development of New Anti-Trypanosoma cruzi Agents

Abstract

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.

Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

“…The thiazole nucleus, which is present in an important class of heterocyclic compounds present in many biologically potent active molecules (45), is also present in the most active compounds of the whole series. Some thiazoles have, in fact, been shown in the literature as schistosomicidal agents (19,46 , respectively.…”

Vanadium polypyridyl compounds as potential antiparasitic and antitumoral agents: New achievements

“…American trypanosomiasis is the major parasitic disease in the Americas, being endemic throughout Latin America, infecting [8][9][10][11][12][13][14] million people and causing more deaths per year in this region than any other parasitic disease (14,000 deaths per year). In addition, the premature disability and the effect of this disease on worker productivity lead to very significant annual losses of resources and industrial productivity.…”

“…Currently, the development of bioactive metal complexes is a promising and attractive approach in the search for new potential drugs for the therapy of parasitic illnesses. Attempts towards developing trypanocidal metal-based compounds have been described [10][11][12]. In particular, we have been successfully working on the development of potential anti-trypanosome and antiLeishmania agents through different approaches [13][14][15][16][17][18][19][20][21][22].…”

Activity on Trypanosoma cruzi, erythrocytes lysis and biologically relevant physicochemical properties of Pd(II) and Pt(II) complexes of thiosemicarbazones derived from 1-indanones

“…Different attempts towards developing trypanosomicidal metal-based compounds have been described [16][17][18][19][20][21][22]. Currently, we are successfully working on the development of metal-based potential antitrypanosomal agents [16,17,22].…”