Activity of Novel Tryptophan Analogs against Trypanosoma cruzi and Leishmania donovani

Abstract

Drugs available for the treatment of Chagas disease and Leishmaniasis are grossly inadequate and have many drawbacks. Most of them are ineffective for the chronic form of the disease. The drugs available are expensive and most need parenteral administration. In addition, most of them are extremely toxic and resistance develops fast. There is an urgent need for new, safe and more effective drugs. As part of the continued search for novel antitrypanosomal drugs, the present study was aimed at the design and synthesis of novel tryptophan analogs which have a potential to inhibit essential trypanosomal enzymes. Some of these compounds have shown significant activity against Trypanosoma brucei brucei in vitro. In the present study, 17 of the most promising compounds were selected and tested for possible activity against the biochemically closely related protozoans Trypanosoma cruzi and Leishmania donovani using in vitro models. Seven compounds showed significant activity against T. cruzi, producing more than 50 % inhibition of multiplication at or below 30 µM concentrations. Four compounds also had significant activity against L. donovani promastigotes in vitro. These findings support the common observation that antiprotozoal drugs tend to exhibit a broad spectrum of activity among various protozoans.

Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological

“…A series of dithiocarbamate-linked analogs produced compounds that showed antiparasitic efficacy at 30 μM against L. donovani and T. cruzi parasites. Moreover, these compounds, chemical structures, as represented in Figure 4, did not present cellular cytotoxicity in in vitro tests [48].…”