Publications

Abstract The therapeutic potential of natural phenolic antioxidants in human diseases associated with oxidative damage has received great attention to date. Appraisal of literature evidences that, in general, antioxidant therapy has enjoyed relative successes in preclinical studies but little benefits in human intervention studies or clinical trials. In fact, despite the huge, largely untapped potential therapeutic benefit of natural phenolic antioxidants, such as vitamins, non-flavonoid and flavonoid compounds, they appear not to be suitable drug candidates. The problem may be related, among others, to their non-drug-likeness properties. Though controversial the results obtained so far confirm the importance of exploring phenolic natural systems as safe templates for the design of new antioxidants. To support the assumption an outlook of the lead structural optimization process to improve ADME properties was given by means of natural hydroxycinnamic acids as a case study. The optimization of drug physicochemical properties and the development of appropriate delivery antioxidant systems can provide in the next future a way out to attain effective therapeutic antioxidant agents.

Abstract Hydroxycinnamic acids (such as ferulic, caffeic, sinapic, and p-coumaric acids) are a group of compounds highly abundant in food that may account for about one-third of the phenolic compounds in our diet. Hydroxycinnamic acids have gained an increasing interest in health because they are known to be potent antioxidants. These compounds have been described as chain-breaking antioxidants acting through radical scavenging activity, that is related to their hydrogen or electron donating capacity and to the ability to delocalize/stabilize the resulting phenoxyl radical within their structure. The free radical scavenger ability of antioxidants can be predicted from standard one-electron potentials. Thus, voltammetric methods have often been applied to characterize a diversity of natural and synthetic antioxidants essentially to get an insight into their mechanism and also as an important tool for the rational design of new and potent antioxidants. The structure-property-activity relationships (SPARs) correlations already established for this type of compounds suggest that redox potentials could be considered a good measure of antioxidant activity and an accurate guideline on the drug discovery and development process. Due to its magnitude in the antioxidant field, the electrochemistry of hydroxycinnamic acid-based antioxidants is reviewed highlighting the structure-property-activity relationships (SPARs) obtained so far.

Abstract 4-Oxo-N-phenyl-4H-chromene-2-carboxamide, C16H11NO3, crystallizes in the space group P2(1)/n and its derivative 7-methoxy-4-oxo-N-p-tolyl-4H-chromene-2-carboxamide, C18H15NO4, forms two polymorphs which crystallize in the space groups P2(1)/c and P (1) over bar. The structures have an anti-rotamer conformation about the C-N bond; however, the amide O atom can be either trans-or cis-related to the O atom of the pyran ring. The latter compound also crystallizes as a hemihydrate, C18H15NO4 center dot 0.5H(2)O, in the space group C2/c. This compound has a similar structure to that of the unsolvated compound.

Abstract The antioxidant responses of Solanum nigrum L. cell suspension cultures to metalaxyl exposure were investigated. An increase in lipid peroxidation and hydrogen peroxide content, for both concentrations tested (20 mg L-1; 40 mg L-1) revealed the response of oxidative metabolism of cell suspensions to metalaxyl. Superoxide dismutase (SOD; EC 1.15.1.1), catalase (CAT; EC 1.11.1.6) and ascorbate peroxidase (APX; EC 1.11.1.11) activities increased, particularly in the highest concentration of metalaxyl used. An analysis by non-denaturing polyacrylamide gel (PAGE) followed by staining for enzyme activity, revealed seven SOD isoenzymes, two CAT isoenzymes, and nine APX isoenzymes. Metalaxyl levels were quantified in the culture medium and results suggest that suspension cells were able to accumulate and/or degrade the fungicide five hours after exposure. SOD, CAT and APX isoenzymes were differently affected by the metalaxyl treatment. Results suggest that the higher concentration of metalaxyl induced oxidative stress to cell suspension cultures of S. nigrum.

Abstract Both experimental and theoretical methodologies were employed in order to study the possibility of excited state oxyluciferin being formed as the result of the decomposition of a neutral dioxetanone. Excitation measurements in water (at different pH values) and in methanol, along with computational calculations, demonstrated that the hydroxyl-benzothiazole group of firefly dioxetanone and six oxyluciferin analogues is only deprotonated in conditions not in line with the firefly bioluminescence reaction. Thus, a new mechanism involving a neutral firefly dioxetanone must be presented in order to explain the chemiexcitation of oxyluciferin. It was also studied for the first time the interaction between a molecule involved in the bioluminescence reaction (neutral firefly dioxetanone) and the real second conformation of firefly luciferase.

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) are 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 qualitative 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 this review. © 2013.

Abstract In this work the synthesis of a new chromone (6-bromo-N-(cyclohex-1-en-1-ylmethyl)-4-oxo-4H-chromene-2-carboxamide) by a strategy performed in three steps is reported. The compound was characterized by NMR (H-1 and C-13) and EIMS and the structure was confirmed by single-crystal X-ray diffraction. The analysis of the X-ray determined that the molecule is built up from two rings, a chromone ring and a cyclohexene ring united by an amide spacer. This new chromone will be valuable for obtaining evidence about the importance of the exocyclic double bound on monoaminoxidase-B (MAO-B) inhibitory activity. (c) 2013 Published by Elsevier B.V.

Abstract Synthetic amino acid-based surfactants possess versatile aggregation properties and are typically more biocompatible and biodegradable than surfactants with conventional headgroups. This opens the possibility of a myriad of specialty applications, namely in pharmaceutics, cosmetics, biomedicine, and nanotemplating chemistry. In this work, we have investigated the interfacial and self-assembling properties in aqueous medium of novel double-chained lysine-based surfactants, with particular focus on the behavior of the dodecyl derivative, 12Lys12. Upon cooling from dilute isotropic micellar solutions, this surfactant crystallizes into micrometer-sized tubular structures that induce gelation of the system. The tubules have been characterized in terms of morphology, assembly process, thermal behavior, and stability, by using differential scanning calorimetry, light and scanning electron microscopy, and deuterium NMR. Possible mechanisms for tubule assembly are discussed, on the basis of surfactant molecular shape, H-bonding and electrostatic interactions, and chirality effects.

Abstract Solanum nigrum L. plants were exposed for 28 days to 100 and 200 mu mol/L copper (Cu) in a hydroponic system to analyze the antioxidant defense response. A dose-dependent reduction in growth (fresh mass of root and shoot, shoot height, and root elongation) with increasing concentration of Cu was observed, whereas Cu treatments did funt affect total chlorophyll and carotefunids content. An enhanced lipid peroxidation, in terms of malondialdehyde (MDA) content, was quantified in shoots when the plants were subjected to the highest Cu level, while in roots MDA levels showed a dose-dependent increase along the increasing Cu concentrations applied. An increase of proline in roots of plants exposed to 200 mu mol/L Cu was found. Antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) did funt show significant changes with respect to control, in both roots and shoots, despite mRNA-specific accumulations varied between Cu levels and organs. Ascorbate peroxidase (APX) was negatively affected in shoots by the highest Cu level. Gene expression of the subtype 2d metallothioneins (MT) revealed to be Cu-enhanced throughout the plant body and correlated with Cu tissue levels, with the other MT1 and MT2 gene members downregulated in roots and upregulated in shoots, contributing more as antioxidants in the latter organs than in Cu homeostasis. MT3s are not involved in Cu homeostasis and phytochelatin (PC) production was enhanced in roots of plants exposed to 200 mu mol/L Cu, contributing to a higher Cu accumulation in these organs.

Abstract Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.