Modeling Parasite Reduction Mechanisms in Chagas Disease

Abstract

Various procedures have been proposed to reduce parasitemia during Chagas disease. Here we analyze in detail models developed to predict the possible outcomes of two of these treatments. The model solutions reproduce available experimental population data and can be used as tools to help researchers to find a cure or, at least, an optimal treatment to reduce cardiac cell damage. In particular, we study how the phase diagram describing the infection outcome is modified by the application of the ganglioside GM1, finding the optimum concentration of the drug in terms of the parameters characterizing its influence on the parasite-host interaction. We also investigate the use of the non-pathogenic parasite T. rangeli to reduce T. cruzi load in a mixed infection, finding that this method is not effective against all T. cruzi strains. Furthermore, we compare phase portraits of the evolution of the disease for a single and a mixed infection, and evaluate the cell damage as a function of the time elapsed between both infections, remarking on the temporary protective effect of the reaction to T. rangeli.

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

“…To determine the purity of the synthesized compounds, high-performance liquid chromatography (HPLC) was used, the percentage total peak area represented by the product peak was determined in a scan of 190-800 nm. All final products (3)(4)(5)(6)(7)(8) showed purities between 97% and 99.9%.…”

“…In Brazil, there are approximately 2-3 million patients with chronic CD and more than 6,000 annual deaths, and CD-related spending accounts for $129 million of the public budget. [4,5] Additionally, current reports demonstrate that the annual global CD-related healthcare costs are approximately $627 million, of which $118 million is spent in the United States. [6] The available drugs for the treatment of CD, benznidazole (1, Bnz) and nifurtimox (2), emerged in the late 1960s and early 1970s [7] (Figure 1).…”

“…The results showed that most compounds were less active than benznidazole. [35] Therefore, in this work, we report six new analogues of Bnz (3)(4)(5)(6)(7)(8), including their design, synthesis and biological evaluation. All these compounds contain a 1,2,3-triazole ring in their structure, and the substitution of the amide functional group with a 1,2,3-triazole ring could be justified because they present similar physicochemical properties, volume and planarity.…”