Publications

Abstract In the present work, Dempster-Shafer Theory (DST) was employed for the implementation of a combined strategy for classification and/or virtual screening of potential anticoccidial drug candidates, based on the combination of the information provided by multiple QSAR models which are derived from different molecular structure representations. The application of such a strategy lead to a classification performance superior to the individual use of QSAR models, achieving accuracy/sensibility/specificity values over 94%/86%/96% and 86%/75%/89% on training and predicting series, respectively. Parallely, the application of such a strategy lead to values of enrichment metrics significantly superiors to the individual use of QSAR models as virtual screening tools. All these results suggest that the use of DST as the theoretical probabilistic base for the implementation of a combined classification and/or virtual screening strategy can be efficiently employed on the process of discovery and development of novel potential anticoccidial candidates, contributing in this way to overcome the emergence of resistance to current therapies.

Abstract In the last couple of years, carbon dots have emerged as a new novel luminescent particle for applications in fluorescence and microscopy in some ways analogous to quantum dots and silicon nanocrystals/particles. As with any fluorescent label or tag, absolute fluorescence intensity, brightness, and particle photostability are a primary concern. In this communication we subsequently show that similar to classical fluorophores, carbon dots located in the near-field, near to Plasmon supporting materials, show enhanced intensities and improved photostabilities.

Abstract The inhibition mechanisms of the firefly luciferase (Luc) by three of the most important inhibitors of the reactions catalysed by Luc, dehydroluciferyl-coenzyme A (L-CoA), dehydroluciferin (L) and L-luciferin (L-LH(2)) were investigated. Light production in the presence and absence of these inhibitors (0.5 to 2 mu M) has been measured in 50 mM Hepes buffer (pH = 7.5), 10 nM Luc, 250 mu M ATP and D-luciferin (D-LH(2), from 3.75 up to 120 mu M). Nonlinear regression analysis with the appropriate kinetic models (Henri-Michaelis-Menten and William-Morrison equations) reveals that L-CoA is a non-competitive inhibitor of Luc (K(i) = 0.88 +/- 0.03 mu M), L is a tight-binding uncompetitive inhibitor (K(i) = 0.00490 +/- 0.00009 mM) and L-LH2 acts as a mixed-type non-competitive-uncompetitive inhibitor (K(i) = 0.68 +/- 0.14 mMand alpha K(i) = 0.34 +/- 0.16 mu M). The Km values obtained for L-CoA, L and L-LH(2) were 16.1 +/- 1.0, 16.6 +/- 2.3 and 14.4 +/- 0.96 mu M, respectively. L and L-LH(2) are strong inhibitors of Luc, which may indicate an important role for these compounds in Luc characteristic flash profile. L-CoA K(i) supports the conclusion that CoA can stimulate the light emission reaction by provoking the formation of a weaker inhibitor.

Abstract Knudsen mass-loss effusion technique was used for measuring the vapor pressures at different temperatures of the following crystalline compounds: diphenylacetic acid, between 357.27 and 379.08 K; triphenylacetic acid, between 418.98 and 436.97 K; 2,2-diphenylpropanoic acid, between 366.08 and 386.00 K; 3,3-diphenylpropanoic acid, between 366.09 and 386.03 K; 3,3,3-triphenylpropanoic acid, between 402.17 and 420.10 K. From the temperature dependence of the vapor pressure of each crystalline compound, the standard (p (0) = 10(5) Pa) molar enthalpies and Gibbs energies of sublimation, at T = 298.15 K, were derived. The measured thermodynamic properties are compared with literature results for phenylacetic and phenylpropanoic acids and correlations for estimation of the vapor pressures from the enthalpy of sublimation and the temperature of fusion of these and other compounds are presented.

Abstract Microwave irradiation offers a considerable advantage over conventional synthesis with rate enhancements and cleaner reactions. Accordingly, a new microwave-assisted method for the synthesis of functionalized chromones was developed allowing the obtention of a library of chromone carboxamides. The method has been shown to present several advantages including operational simplicity, good performance, significant reduction in reaction time, less formation of by-products, and easier work-up.

Abstract Two series of novel chromone derivatives were synthesized and investigated for their ability to inhibit the activity of monoamine oxidase. The SAR data indicate that chromone derivatives with substituents in position 3 of gamma-pyrone nucleus act preferably as MAO-B inhibitors, with IC50 values in the nanomolar to micromolar range. Almost all chromone 3-carboxamides display selectivity toward MAO-B. Identical substitutions on position 2 of gamma-pyrone nucleus result in complete loss of activity in both isoforms (chromones 2-12 except 3 and 5). Notably, chromone (19) exhibits an MAO-B IC50 of 63 nM, greater than 1000-fold selectivity over MAO-A, and behaves as a quasi-reversible inhibitor. Docking experiments onto the MAO binding of the most active compound highlight different interaction patterns among the isoforms A and B. The differential analysis of the solvation effects among the chromone isomers gave additional insight about the superior outline of the 3-substituted chromone derivatives.

Abstract A new, non-polarizable force field model (FFM) for imidazolium-based, room-temperature ionic liquids (RTILs), 1-ethyl-3-methyl-imidazolium tetrafluoroborate and 1-butyl-3-methyl-imidazolium tetrafluoroborate, has been developed. Modifying the FFM originally designed by Liu et al. (J. Phys. Chem. B, 2004, 108, 12978-12989), the electrostatic charges on interacting sites are refined according to partial charges calculated by explicit-ion density functional theory. The refined FFM reproduces experimental heats of vaporization, diffusion coefficients, ionic conductivities, and shear viscosities of RTILs, which is a significant improvement over the original model (Zh. Liu, Sh. Huang and W. Wang, J. Phys. Chem. B, 2004, 108, 12978-12989). The advantages of the proposed procedure include clarity, simplicity, and flexibility. Expanding the functionality of our FFM conveniently only requires modification of the electrostatic charges. Our FFM can be extended to other classes of RTILs as well as condensed matter systems in which the ionic interaction requires an account of polarization effects. © 2011 the Owner Societies.

Abstract Phenolic compounds constitute a diverse group of secondary metabolites which are present in both grapes and wine. The phenolic content and composition of grape processed products (wine) is greatly influenced by the technological practice to which grapes are exposed. During the handling and maturation of the grapes several chemical changes may occur with the appearance of new compounds and/or disappearance of others, and consequent modification of the characteristic ratios of the total phenolic content as well as of their qualitative and quantitative profile. The non-volatile phenolic composition of grapes and wines, the biosynthetic relationships between these compounds, and the most relevant chemical changes occurring during processing and storage will be highlighted in the present study.

Abstract Long chain alkyl hydroxycinnamates (8-21) were synthesized from the corresponding half esters of malonic acid (5-7) and benzaldehyde derivatives by Knoevenagel condensation. The total antioxidant capacity of these hydroxycinnamyl esters was evaluated using DPPH and ABTS assays. The observed antioxidant activity was highest for esters of caffeic acid followed by sinapic esters and ferulic esters. The parameters for drug-likeness of these hydroxycinnamyl esters were also evaluated according to the Lipinski's 'rule-of-five'. All the ester derivatives were found to violate one of the Lipinski's parameters (cLogP >5), even though they have been found to be soluble in protic solvents. The predictive topological polar surface area (TPSA) data allow concluding that they could have a good capacity for penetrating cell membranes. Therefore, one can propose these novel lipophilic compounds as potential antioxidants for tackling oxidative processes.