Inovação do método MIA-QSAR: aplicação para doenças tropicais negligenciadas

Multivariate image analysis applied to the quantitative structure-activity relationships (MIA-QSAR) is a 2D QSAR technique that has been presenting promising outcomes for the development of new drug candidates, due to its simplicity, rapidity and low cost. In this way, the present study aims at introducing, consolidating and improving the new dimensions named aug-MIA-QSAR and aug-MIA-QSARcolor, as well as applying them to the study of neglected diseases, in order to obtain new drug targets using chemico-biological interpretation of the MIA molecular descriptors. Four compound data sets with experimental bioactivities against Chagas disease, malaria, dengue and schistosomiasis were evaluated using three approaches: MIA-QSARt, aug-MIA-QSAR and aug-MIA-QSARcolor. In general, representations of atoms as spheres with different colors and sizes proportional to the corresponding van der Waals radii (aug-MIA approaches) improved the predictive ability and interpretability in all data sets. The use of colors proportional to the Pauling´s electronegativity showed that MIA descriptors are capable of identifying periodic properties relevant for the studied activity. Finally, solid colors instead of spotlighted atoms allowed a correct identification of atoms by means of pixel values in the studies for malaria, dengue and schistosomiasis, which were, subsequently, useful for the chemical interpretation related to the bioactivity. It can be inferred that semicarbazones and thiosemicarbazones derivative with a tri-substituted ring in R1 group and a trifluoro methyl group in the R 3 position instead of a chlorine antitripanossoma resulted in higher activity. The antimalarial activity of quinolon-4(1H)imines can be improved if: 1) R1 and R2 are electron donor groups, 2) R3 has long aminoalkyl chains, and 3) R4 possesses substituents with big atomic volume. In the study for dengue, it was found that tetrapeptides with unbranched small size amino acids in the A1 and A4 positions can increase the substrate affinity (Km) to the NS3 protein, and when in A1 and A2 positions, the substrate cleavage rate (kcat). On the other hand, acidic amino acids in the A2 and A4 positions were found to be related with low substrate affinity to the NS3 protein and when present in A1, with low substrate cleavage rate. Finally, the presence of metoxy substituents in R1 (or R2) and R5 in the neolignan backbone can favor their antischistosomal activity.

Avaliação do potencial de uso agrícola da fluorita com óxido silício (AgroSiCa), derivado da fabricação de fertilizantes fosfatados

Phosphate fertilizers are critical for crop production in tropical soils, which are known for having high phosphate-fixing capacity and aluminium saturation, as well as low pH and calcium contents. Fluorine is a component of many phosphate rocks used to make phosphate fertilizers, via a process that generates hexafluorosilicic acid (H2SiF6). While many treatment technologies have been proposed for removal of fluorine in industrial facilities, little attention has been given to a process of neutralizing H2SiF6 with calcium oxide aiming to find out an alternative and sustainable use of a by-product with a great potential for beneficial use in tropical agriculture. This study evaluated the effect of a by-product of phosphoric acid production (fluorite with silicon oxide, hereafter called AgroSiCa) in levels of phosphorus (P), calcium (Ca), silicon (Si), aluminum (Al) and fluorine (F) and some others parameters in soils as on growth of soybean and corn. Experiments were conducted in a greenhouse condition at the Federal University of Lavras (UFLA), Lavras, Minas Gerais, using different types of soils in tropical regions and different doses of AgroSiCa. The application of AgroSiCa resulted in a slight increase in soil pH and significant increases in calcium, phosphorus and silicon in the soil solution and the shoots of corn and soybeans. We also found very low levels of fluoride in all soil leachates. A significant reduction of labile aluminum levels found in all soils after the cultivation of corn and soybeans. In sum, AgroSiCa improved soil properties and contributed to better growth of both cultures. In sum, AgroSiCa improved soil properties and contributed to a better growth of both crops. Our results show that reacting H2SiF6 derived from the wet-process phosphoric acid production with calcium oxide leads to a by-product with potential for agricultural use, especially when applied in highly-weathered soils. Besides providing calcium and silicon to plants, the use of such by-product in soils with high phosphate-fixing capacity and high aluminium saturation delivers additional benefits, since fluoride and silicon can play an important role in improving soil conditions due to the formation of less plant-toxic forms of aluminium, as well as upon decreasing phosphate fixation, thus improving root development and making fertilizer-derived phosphate more available for plant growth.