Evaluation of natural and synthetic compounds according to their antioxidant activity using a multivariate approach

The antioxidant activity of natural and synthetic compounds was evaluated using five in vitro methods: ferric reducing/antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydradzyl (DPPH), oxygen radical absorption capacity (ORAL), oxidation of an aqueous dispersion of linoleic acid accelerated by azo-initiators (LAOX), and oxidation of a meat homogenate submitted to a thermal treatment (TBARS). All results were expressed as Trolox equivalents. The application of multivariate statistical techniques suggested that the phenolic compounds (caffeic acid, carnosic acid, genistein and resveratrol), beyond their high antioxidant activity measured by the DPPH, FRAP and TBARS methods, showed the highest ability to react with the radicals in the ORAC methodology, compared to the other compounds evaluated in this study (ascorbic acid, erythorbate, tocopherol, BHT, Trolox, tryptophan, citric acid, EDTA, glutathione, lecithin, methionine and tyrosine). This property was significantly correlated with the number of phenolic rings and catecholic structure present in the molecule. Based on a multivariate analysis, it is possible to select compounds from different clusters and explore their antioxidant activity interactions in food products.

Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-Hydrazides Active against MRSA

In this preliminary study eighteen p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. The computer programs Sybyl and CORINA were used, respectively, for the design and three-dimensional conversion of the ligands. Molecular interaction fields were calculated using GRID program. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response.

Crystal structure of 1,2-bis(4-fluoro-2-methylphenyl)ditelluride, [Te(C7H6F)](2)

C14H12F2Te2, monoclinic, C12/c1 (no. 15), a = 23.650(2) angstrom, b = 7.792(1) angstrom, c = 7.556(1) angstrom, beta = 106.47(1)degrees, V = 1335.2 angstrom(3), Z = 4, R-gt(F) = 0.041, wR(ref)(F-2) = 0.123, T= 98 K.

Crystal structure of Trypanosoma cruzi dihydroorotate dehydrogenase from Y strain

Trypanosoma cruzi is the etiological agent of Chagas` disease, a pathogenesis that affects millions of people in Latin America. Here, we report the crystal structure of dihydroorotate dehydrogenase (DHODH) from T cruzi strain Y solved at 2.2 angstrom resolution. DHODH is a flavin mononucleotide containing enzyme, which catalyses the oxidation Of L-dihydroorotate to orotate, the fourth step and only redox reaction in the de novo biosynthesis of pyrimidine nucleotides. Genetic studies have shown that DHODH is essential for T cruzi survival, validating the idea that this enzyme can be considered an attractive target for the development of antichagasic drugs. In our work, a detailed analysis of T cruzi DHODH crystal structure has allowed us to suggest potential sites to be further exploited for the design of highly specific inhibitors through the technology of structure-based drug design. (c) 2008 Elsevier Inc. All rights reserved.

The anti-cancer agent guttiferone-A permeabilizes mitochondrial membrane: Ensuing energetic and oxidative stress implications

Guttiferone-A (GA) is a natural occurring polyisoprenylated benzophenone with cytotoxic action in vitro and anti-tumor action in rodent models. We addressed a potential involvement of mitochondria in GA toxicity (1-25 mu M) toward cancer cells by employing both hepatic carcinoma (HepG2) cells and succinate-energized mitochondria, isolated from rat liver. In HepG2 cells GA decreased viability, dissipated mitochondrial membrane potential, depleted ATP and increased reactive oxygen species (ROS) levels. In isolated rat-liver mitochondria GA promoted membrane fluidity increase, cyclosporine A/EGTA-insensitive membrane permeabilization, uncoupling (membrane potential dissipation/state 4 respiration rate increase), Ca(2+) efflux, ATP depletion, NAD(P)H depletion/oxidation and ROS levels increase. All effects in cells, except mitochondrial membrane potential dissipation, as well as NADPH depletion/oxidation and permeabilization in isolated mitochondria, were partly prevented by the a NAD(P)H regenerating substrate isocitrate. The results suggest the following sequence of events: 1) GA interaction with mitochondrial membrane promoting its permeabilization; 2) mitochondrial membrane potential dissipation; 3) NAD(P)H oxidation/depletion due to inability of membrane potential-sensitive NADP(+) transhydrogenase of sustaining its reduced state; 4) ROS accumulation inside mitochondria and cells; 5) additional mitochondrial membrane permeabilization due to ROS; and 6) ATP depletion. These GA actions are potentially implicated in the well-documented anti-cancer property of GA/structure related compounds. (C) 2011 Elsevier Inc. All rights reserved.

HPLC separation, NMR and QTOF/MS/MS structure elucidation of a prominent nitric oxide donor agent based on an isomeric composition of a nitrosyl ruthenium complex

A new and promising nitrosyl ruthenium complex, [Ru(NO)(bdqi-COOH)(terpy)](PF(6))(3), bdqi-COOH is 3,4-diiminebenzoic acid and terpy is 2,2`-terpyridine, has been synthesized as a NO donor agent. The procedure used for [Ru(NO)(bdqi-COOH)(terpy)](PF(6))(3) synthesis has, apparently, yielded the formation of two isomers in which the ligand bdqi-COOH appears to be coordinated in its reduced form (bdcat-COOH), which could have differences in their pharmacological properties. Therefore, it was intended to separate the two possible isomers by high-performance liquid chromatography (HPLC) and to characterize them by high resolution mass spectrometry (QTOF MS) and by magnetic nuclear resonance spectroscopy (NMR). The results obtained by MS showed that the ESI-MS mass spectra of both HPLC column fractions, e.g. peak 1 and peak 2, are essentially equal, showing that both isomers display nearly identical gas-phase behavior with clusters of isotopologue ions centered at m/z 573, m/z 543 and m/z 513. Regarding the NMR analysis, the results showed that the positional isomerism is located in the bdqi-COOH ligand. From the observed results it can be concluded that the synthesis procedure that has been used results in the formation of two [Ru(terpy)(bdqi-COOH)NO](PF(6))(3) isomers. (c) 2009 Elsevier B.V. All rights reserved.

Trypanocidal structure-activity relationship for cis- and trans-methylpluviatolide

The trypanocidal activity of racemic mixtures of cis- and trans-methylpluviatolides was evaluated in vitro against trypomastigote forms of two strains of Trypanosoma cruzi, and in the enzymatic assay of T. cruzi gGAPDH. The cytotoxicity of the compounds was assessed by the MTT method using LLC-MK2 cells. The effect of the compounds on peroxide and NO production were also investigated. The mixture of the trans stereoisomers displayed trypanocidal activity (IC(50) similar to 89.3 mu M). Therefore, it was separated by chiral HPLC, furnishing the and (+) (-)-enantiomers. Only the (-)-enantiomer was active against the parasite (IC(50) similar to 18.7 mu M). Despite being inactive, the (+)-enantiomer acted as an antagonistic competitor. Trans-methylpluviatolide displayed low toxicity for LLC-MK(2) cells, with an IC(50) of 6.53 mM. Furthermore, methylpluviatolide neither inhibited gGAPDH activity nor hindered peroxide and NO production at the evaluated concentrations. (C) 2008 Elsevier Ltd. All rights reserved.

Schistosomicidal and trypanocidal structure-activity relationships for (+/-)-licarin A and its (-)- and (+)-enantiomers

(+/-)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (-)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC(50) value of 53.57 mu M and moderate trypanocidal activity with an IC(50) value of 127.17 mu M. On the other hand, the (-)-enantiomer (2), displaying a LC(50) value of 91.71 mu M, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC(50) of 23.46 mu M) than enantiomer 3, which showed an IC(50) value of 87.73 mu M. Therefore, these results suggest that (+/-)-licarin A (1) and (-)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents. (C) 2011 Elsevier Ltd. All rights reserved.

Analysis of Liquid Crystalline Nanoparticles by Small Angle X-Ray Diffraction: Evaluation of Drug and Pharmaceutical Additives Influence on the Internal Structure

The goal of this work was to study the liquid crystalline structure of a nanodispersion delivery system intended to be used in photodynamic therapy after loading with photosensitizers (PSs) and additives such as preservatives and thickening polymers. Polarized light microscopy and light scattering were performed on a standard nanodispersion in order to determine the anisotropy of the liquid crystalline structure and the mean diameter of the nanoparticles, respectively. Small angle X-ray diffraction (SAXRD) was used to verify the influence of drug loading and additives on the liquid crystalline structure of the nanodispersions. The samples, before and after the addition of PSs and additives, were stable over 90 days, as verified by dynamic light scattering. SAXRD revealed that despite the alteration observed in some of the samples analyzed in the presence of photosensitizing drugs and additives, the hexagonal phase still remained in the crystalline phase. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2849-2857, 2011

von Wright`s Therapy to Jorgensen`s Syndrome

In his last papers about deontic logic, von Wright sustained that there is no genuine logic of norms. We argue in this paper that this striking statement by the father of deontic logic should not be understood as a death sentence to the subject. Rather, it indicates a profound change in von Wright`s understanding about the epistemic and ontological role of logic in the field of norms. Instead of a logical constructivism of deontic systems revealing a necessary structure of prescriptive discourse, which marked his earlier efforts, he adopted the view that such systems should be seem as mere objects of comparison, i.e. as providing practical standards of rationality for norm-giving activity. Within such view he proposed an interpretation of standard deontic logic in such a way to free deontic logicians from the philosophical difficulties related to the so-called Jorgensen`s dilemma and deontic paradoxes. This effort, as we claim in the present paper, is an application of Wittgenstein`s therapeutic method to dissolve philosophical difficulties caused by the use of logical tools to model relations between norms.

Hierarchical determinants of capital structure

We analyze the influence of time-, firm-, industry- and country-level determinants of capital structure. First, we apply hierarchical linear modeling in order to assess the relative importance of those levels. We find that time and firm levels explain 78% of firm leverage. Second, we include random intercepts and random coefficients in order to analyze the direct and indirect influences of firm/industry/country characteristics on firm leverage. We document several important indirect influences of variables at industry and country-levels on firm determinants of leverage, as well as several structural differences in the financial behavior between firms of developed and emerging countries. (C) 2010 Elsevier B.V. All rights reserved.

Stability property of matchings is a natural solution concept in coalitional market games

Stability of matchings was proved to be a new cooperative equilibrium concept in Sotomayor (Dynamics and equilibrium: essays in honor to D. Gale, 1992). That paper introduces the innovation of treating as multi-dimensional the payoff of a player with a quota greater than one. This is done for the many-to-many matching model with additively separable utilities, for which the stability concept is defined. It is then proved, via linear programming, that the set of stable outcomes is nonempty and it may be strictly bigger than the set of dual solutions and strictly smaller than the core. The present paper defines a general concept of stability and shows that this concept is a natural solution concept, stronger than the core concept, for a much more general coalitional game than a matching game. Instead of mutual agreements inside partnerships, the players are allowed to make collective agreements inside coalitions of any size and to distribute his labor among them. A collective agreement determines the level of labor at which the coalition operates and the division, among its members, of the income generated by the coalition. An allocation specifies a set of collective agreements for each player.

The economic determinants of the Brazilian nominal term structure of interest rates

The purpose of this study is to identify the effects of monetary policy and macroeconomic shocks on the dynamics of the Brazilian term structure of interest rates. We estimate a near-VAR model under the identification scheme proposed by Christiano et al. (1996, 1999). The results resemble those of the US economy: monetary policy shocks that flatten the term structure of interest rates. We find that monetary policy shocks in Brazil explain a significantly larger share of the dynamics of the term structure than in the USA. Finally, we analyse the importance of standard macroeconomic variables (e. g. GDP, inflation and measure of country risk) to the dynamics of the term structure in Brazil.

The structure of worker compensation in Brazil, with a comparison to France and the United States

We employ comprehensive linked employer-employee data for Brazil to analyze wage determinants and compare results to Abowd et al. (2001) for French and U.S. manufacturing. While returns to human capita in Brazilian manufacturing exceed those of the other countries, occupation and gender differentials are similar. The worker-characteristics component accounts for much of the greater wage inequality in Brazil, but the establishment-fixed component has scant explanatory power. Thus, firm-or industry-level factors offer little scope for explaining the differences in wage inequality. Brazil`s wage structure resembles that of France, a country with some similarity in labor market institutions.

A costs structure analysis of the Brazilian sugar and ethanol companies

The Brazil consolidated itself as the largest world producer of sugarcane, sugar and ethanol. The creation of the Programa Nacional do Alcool - PROALCOOL and the growing use of cars with flexible motors were some of the factors that helped to motivate still more the production. Evolutions in the agricultural and industrial research did the Brazilian competitiveness in sugar and ethanol globally elevated, what is evidenced when comparing the amount produced at the country and the production costs, which turned a big one differential. Therefore, the administration of costs is of great relevance to the sugar and ethanol companies, for representing a significant rationalization in the production processes, with economy of resources and the reach of better earnings, besides reducing the operational risk pertinent at the fixed costs of production. Thus, the present work has for objective to analyze the costs structure of sugar and ethanol companies of the Center-south area of the country through an empiric-analytical study based in methodologies and concepts extracted of the costs accounting. It is verified that great part of the costs and operational expenses have variable behavior, a positive factor for the sector reducing the operational risk of the activity. The main restraint of this study is the sample of five years and 10% of the number of plants in Brazil that although they represent 30% of the national production, don`t allow the generalization of the model.