Chagas disease is a tropical parasitic disease that is caused by Trypanosoma cruzi and causes 12,000 deaths per year, mainly in Latin America. The available drugs for treating have severe limitations, including poor efficacy and high toxicity. One way to overcome these limitations is targeting priority molecules with computational tools to direct in vitro assays against validated targets. Farnesyl pyrophosphate synthase (E.C. 2.5.1.10) is an enzyme that participates in the initial stage of sterol biosynthesis, and its inhibition causes damage to membrane integrity, leading to parasite death. With the aim to identify potential inhibitors against this target from T. cruzi, hierarchical virtual screening approaches were performed through a combination of ligand-based pharmacophore models and molecular docking. First, pharmacophore model filtering resulted in 15,154 molecules that had the minimum structural requirements for inhibition (QFIT > 0). These molecules were subsequently submitted to molecular docking routine, which resulted in 11,762 molecules (Grid Score between -232.74 to -0.96 kcal mol-1). The top 30 ranked molecules in these approaches were grouped in self-organizing maps. These analyses showed four promising compounds from natural products that mimic the major interactions present in the substrate/inhibitor, which indicates that these molecules can be assayed by in vitro experiments.

This study proposes an optimized procedure for the determination of inorganic antimony species in natural waters using hydride generation atomic fluorescence spectrometry (HG AFS) and continuous flow system. The variables of the hydride generation system, such as pre-reduction time, hydrochloric acid concentration and sodium tetrahydroborate concentration, were evaluated using full factorial design at two levels and Doehlert design. After optimized experimental conditions, the method allowed the determination of antimony with limits of detection and quantification of 9 and 30 ng L-1, respectively. The precision (RSD) of the method was < 5% and the accuracy was confirmed by the analysis of certified reference material (SLRS-4, River water for trace metals). The method was successfully applied for inorganic antimony speciation in water samples collected in Salvador City, Bahia State, Brazil. In mineral water, total Sb concentrations ranged from 0.26 to 0.30 µg L-1, whereas the concentrations of SbIII were below 0.03 µg L-1. On the other hand, in natural surface waters, the quantifiable concentration of total Sb and SbIII ranged from 0.41 to 1.23 µg L-1 and 0.23 to 1.04 µg L-1, respectively. The highest average concentrations of Sb were obtained in regions with the largest urban influence, ratifying the anthropogenic impact in water bodies.