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.

Relação entre governança corporativa e gerenciamento de resultados: um estudo em empresas brasileiras listadas na BM&FBOVESPA

The objective of this work was to identify a possible relation between corporate governance, through the structure of the boards of directors and the levels of earnings management of Brazilian public companies. The study is characterized as a descriptive, of a hypothetical-deductive nature, with quantitative approach guided by the estimation model proposed by Kang and Sivaramakrishnan (1995). The sample was comprised by 56 companies, analyzed in the period from 2011 to 2014. The information on the companies were extracted from Economatica databank. For the data analysis, we used multivariate techniques, such as Pearson correlation and panel data in POLS, Fixed Effects and Random Effects approaches. Furthermore, we applied the mean comparison test ANOVA. The results obtained show that, generally, the organizations tend to follow the profile of boards of directors recommended by the codes of corporative governance. However, the characteristics of the composition of the board, regarding its size and the duality of positions that are not yet sufficient to be considered capable of inhibiting the discretionary practice of the studied companies. Relative the control variables, only size and return on equity presented no significant relation with result management. It is important to highlight that literature point many factors that explain the different impacts caused by the formation of the administration board in different regions or countries. Among the factors pointed, we highlight the legal system of the country, the economic and political development, the importance of the capital market, and the level of accounting education.