We modified the thiazolidinic ring at positions N3, C4, and C5, yielding compounds 6-24. Compounds with a phenyl at position N3, 15-19, 22-24, exhibited better inhibitory properties for cruzain and against the parasite than 2-iminothiazolidin-4-one 5. We were able to identify one high-efficacy trypanocidal compound, 2-minothiazolidin-4-one 18, which inhibited the activity of cruzain and the proliferation of epimastigotes and was cidal for trypomastigotes but was not toxic for splenocytes. Having located some of the structural determinants of the trypanocidal properties, we subsequently wished to determine if the exchange of the thiazolidine for a thiazole ring leaves the functional properties unaffected. We therefore tested thiazoles 26-45 and observed that they did not inhibit cruzain, but they exhibited trypanocidal effects. Parasite development was severely impaired when treated with 18, thus reinforcing the notion that this class of heterocycles can lead to useful cidal agents for Chagas disease.

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The use of Solid Lipid Nanoparticles (SLN) has become a very popular approach in the development of innovative pharmaceutical drug delivery systems. The first step is the assessment the lipids' suitability. This paper is focused on the physicochemical characterization of lipids, namely cetyl alcohol and cetearyl alcohol, for the production of SLN. The bulk lipids were analyzed by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD) without any treatment, after tempering the raw materials (bulk lipid) for 1 hour at 80 °C, and after their spray-drying process. Hydrophilic-Lipophilic Balance (HLB) values were determined using a combination of surfactants (polysorbate 20 and trioleate sorbitan) for the production of the hot o/w emulsion. Results of DSC and WAXD showed that after the thermal stress applied to the bulk lipids, both the melting point and the intensity of the refractogram peaks have decreased. Cetyl alcohol and cetearyl alcohol crystallized in more unstable polymorphic forms, which anticipate the suitability of these lipids for the production of SLN. The best HLB values obtained for the produced emulsions were 15.5, 16.0, and 16.7, combining accepted surfactants. The results showed that both cetearyl alcohol and cetyl alcohol are adequate lipids for the development of stable SLN.

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