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.

Capacidade combinatória de linhagens e seleção de híbridos de sorgo sacarino

Sweet sorghum figure as an alternative feedstock for ethanol production. The establishment of this culture in Brazilian production chain depends on the development of more productive and adapted cultivars. The aim of this study was to evaluate the general combining ability (GCA) of sweet sorghum lines and specific combining ability (SCA) of hybrid combinations as the agronomic and technological traits, and additionally to identify promising hybrid combinations for evaluation in advanced trials. Five restorer lines (R) and four male-sterile lines (A) were used in a partial cross diallel yielding 20 hybrids. The parental lines, hybrids and one check were evaluated in experiments carried out in a rectangular lattice design 5x6 with three replicates in two locations. The following traits were measured: flowering time, plant height, green mass yield, dry matter percentage, dry matter yield, juice extraction, total soluble solids content, sucrose content, purity, reducing sugars content, fiber content, sugars reducing total content, total recoverable sugars, hydrous ethanol, tons of per hectare, and ethanol production. There were differences between locations and genotypes for the traits. There was a significant effect of the genotype by environment interaction for most characters, except juice extraction, purity and reducing sugars content. There were a significant effect of GCA and SCA for most traits, indicating that additive and non-additive effects affect the phenotypic expression. Considering the effects of the GCA, the A line 201402B022-A, and R lines BRS 511, CMSXS643, and CMSXS646 were considered promising for exploration as parents in breeding programs of sweet sorghum in order to increase the ethanol production and the quality of the feedstock.The hybrids 201402B010-A x BRS 511, 201402B010-A x BRS 508, 201402B010-A x CMSXS646, 201402B022-A x BRS 511, 201402B022-A x CMSXS643, 201402B022-A x CMSXS646, 201402B022-A x CMSXS647 were the most promising for ethanol yield.