Publications

Abstract Anthocyanins are potential food colorants due to their color, low toxicity and biological properties. However, the low chemical stability of anthocyanins has limited their use. In this work, the thermal stability of cyanidin-3-O-glucoside (cy3glc) (major blackberry anthocyanin) and blackberry purees through molecular inclusion with beta-cyclodextrin (beta-CD) was assessed. Complexation with beta-CD showed a thermal stabilization of cy3glc, resulting on a decrease of the degradation rate constant (k) and in several alterations in the cy3glc-beta-CD DSC thermogram. To assess the bioaccessibility of blackberry anthocyanins, the stability of blackberry purees through simulated in vitro digestion was also studied. Despite the rapid degradation of anthocyanins observed within the first minutes of simulated intestinal digestion, complexation with beta-CD allowed anthocyanins degradation to be slowed down. The results obtained demonstrate the ability of beta-CD to increase blackberry anthocyanins thermal stability and also to decrease the rate of degradation of these pigments under simulated gastrointestinal conditions.

Abstract Aromatic diamines and naphthyl-substituted benzidines (BDB, TPB, TPD, NPB, alpha-NPD, beta-NPB, TNB) are listed as one of the best series available of hole transport materials used as thin films in organic electronics (OLEDs, OPVs). High-quality, homogeneous and compact thin films (ae 300 nm of thickness) of this compound series were prepared by a physical vapor deposition procedure. SEM and XRD characterizations evidence the amorphous nature of the thin films of NPB, alpha-NPD, beta-NPB and TNB, prepared onto ITO and gold surfaces by a controlling mass flow rate. The semiconducting behavior of this class of pi-conjugated materials was investigated through UV-vis characterization by the determination of optical band gaps (ae 3 eV). According to DSC, SEM and XRD analyses, the materials evidenced an amorphous structure and high thermal stability in the glassy state. Analyzing the melting properties, the ratio T (g)/T (m) = 2/3 was observed for TPB and NPB, which have a higher molecular symmetry, while T (g)/T (m) = 3/4 was observed for the asymmetric beta-NPB and TPD. The first accurate measurements of the vapor pressures and thermodynamic properties of phase transition were obtained for the most common hole transport material (NPB) in OLEDs. The relative stability of the crystalline phases of the diamine derivatives (BDB, TPB, NPB) was found to be enthalpically driven, increasing linearly with the molar volume of the compound.

Abstract The present work presents an extensive literature survey and analysis of the heat capacity and thermodynamic properties of fusion, vaporization, and sublimation for the linear hydrocarbons and several terminally substituted homologous series. The successive introduction of methylene groups on the relative stability of the solid and liquid phases is analyzed and discussed based on the chain length dependence of the enthalpies, entropies, and Gibbs energies of phase transition. An oddeven alternation is observed in the fusion and sublimation equilibria. The improved packing patterns of even-numbered n-alkanes is reflected in higher values of melting temperatures and thermodynamic properties of phase transition. Molar heat capacities in liquid phase of n-alkanes derivatives exhibit a linear dependence with the chain length by an increment of 31 +/- 2 JK(-1)mol(-1) per methylene group (-CH2-). A contribution of 4.95 kJmol(-1) per methylene group (value corrected for 298.15 K) is derived for the increment of the enthalpy of vaporization. A constant value for the specific enthalpy of vaporization is observed for long chain compounds: 360 Jg(1). As predictable, the enthalpy of vaporization is higher for groups that can form hydrogen-bonding interactions than for plain hydrocarbons. Concerning the monohalogenated alkanes, a clear increasing of enthalpy of vaporization for the larger halogen groups is observed. Moreover, the thermodynamic results indicate that along the fusion of n-alkanes and n-alkanols, there is a decrease of around 40% in the magnitude of intermolecular interactions.

Abstract The biological effects attributed to nitric oxide ((NO)-N-center dot) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age-related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N-O bond enabled the development of several classes of compounds with potential clinical interest, among which (NO)-N-center dot and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N-O-based drugs for age-related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.

Abstract Staphylococcus aureus is a microorganism resident in the skin and nasal membranes with a dreadful pathogenic potential to cause a variety of community and hospital-acquired infections. The frequency of these infections is increasing and their treatment is becoming more difficult. The ability of S. aureus to form biofilms and the emergence of multidrug-resistant strains are the main reasons determining the challenge in dealing with these infections. S. aureus' infectious capacity and its success as a pathogen is related to the expression of virulence factors, among which the production of a wide variety of toxins is highlighted. For this reason, a better understanding of S. aureus toxins is needed to enable the development of new strategies to reduce their production and consequently improve therapeutic approaches. This review focuses on understanding the toxin-based pathogenesis of S. aureus and their role on infectious diseases.

Abstract Mitochondrial function and regulation of redox balance is fundamental in controlling cellular life and death pathways. Antioxidants have been used to counteract disruption of redox networks, normally associated with progressive loss of cell homeostasis and disease pathophysiology, although therapeutic success is limited mainly due to pharmacokinetic drawbacks. Attempts to improve mitochondrial function in a range of diseases spurred active drug discovery efforts. Currently, the most effective strategy to deliver drugs to mitochondria is the covalent link of lipophilic cations to the bioactive compound. Although targeting mitochondrial oxidative stress with antioxidants has been demonstrated, clinical use has been hampered by several challenges, with no FDA approved drug so far. Development of new mitochondriotropic antioxidant agents based on dietary polyphenols has recently gained momentum. Due to their nature, mitochondria-targeted multi-functional antioxidants can trigger stress responses and contribute to tissue protection through hormesis mechanisms, inhibiting excessive mitochondrial ROS production and associated diseases.

Abstract Objectives: The 'One Health' concept recognises that the health of humans, animals and the environment are interconnected. Therefore, knowledge on the behaviour of micro-organisms from the most diverse environmental niches is important to prevent the emergence and dissemination of antimicrobial resistance. Wild animals are known to carry antimicrobial-resistant micro-organisms with potential public health impact. However, no data are available on the behaviour of sessile bacteria from wild animals, although antimicrobial resistance is amplified in biofilms. This study characterised the ciprofloxacin susceptibility and the adhesion and biofilm formation abilities of 14 distinct Aeromonas spp. (8 Aeromonas salmonicida, 3 Aeromonas eucrenophila, 2 Aeromonas bestiarum and 1 Aeromonas veronii) isolated from wild animals and already characterised as resistant to beta-lactam antibiotics. Methods: The ciprofloxacin MIC was determined according to CLSI guidelines. A biofilm formation assay was performed by a modified microtitre plate method. Bacterial surface hydrophobicity was assessed by sessile drop contact angle measurement. Results: All Aeromonas spp. strains were resistant to ciprofloxacin (MICs of 6-60 mu g/mL) and had hydrophilic surfaces (range 2-37 mJ/m(2)). These strains were able to adhere and form biofilms with distinct magnitudes. Biofilm exposure to 10 x MIC of ciprofloxacin only caused low to moderate biofilm removal. Conclusions: This study shows that the strains tested are of potential public health concern and emphasises that wild animals are potential reservoirs of multidrug-resistant strains. In fact, Aeromonas spp. are consistently considered opportunistic pathogens. Moreover, bacterial ability to form biofilms increases antimicrobial resistance and the propensity to cause persistent infections.

Abstract Background. The "One Health" concept recognizes that human health and animal health are interdependent and bound to the health of the ecosystem in which they (co)exist. This interconnection favors the transmission of bacteria and other infectious agents as well as the flow of genetic elements containing antibiotic resistance genes. This problem is worsened when pathogenic bacteria have the ability to establish as biofilms. Therefore, it is important to understand the characteristics and behaviour of microorganisms in both planktonic and biofilms states from the most diverse environmental niches to mitigate the emergence and dissemination of resistance. Methods. The purpose of this work was to assess the antibiotic susceptibility of four bacteria (Acinetobacter spp., Klebsiella pneumoniae, Pseudomonas fluorescens and Shewanella putrefaciens) isolated from wild animals and their ability to form biofilms. The effect of two antibiotics, imipenem (IPM) and ciprofloxacin (CIP), on biofilm removal was also assessed. Screening of resistance genetic determinants was performed by PCR. Biofilm tests were performed by a modified microtiter plate method. Bacterial surface hydrophobicity was determined by sessile drop contact angles. Results. The susceptibility profile classified the bacteria as multidrug-resistant. Three genes coding for beta-lactamases were detected in K. pneumoniae (TEM, SHV, OXA-aer) and one in P. fluorescens (OXA-aer). K. pneumoniae was the microorganism that carried more beta-lactamase genes and it was the most proficient biofilm producer, while P. fluorescens demonstrated the highest adhesion ability. Antibiotics at their MIC, 5 x MIC and 10 x MIC were ineffective in total biofilm removal. The highest biomass reductions were found with IPM (54% at 10 x MIC) against K. pneumoniae biofilms and with CIP (40% at 10 x MIC) against P. fluorescens biofilms. Discussion. The results highlight wildlife as important host reservoirs and vectors for the spread of multidrug-resistant bacteria and genetic determinants of resistance. The ability of these bacteria to form biofilms should increase their persistence.

Abstract There has been a substantial research effort to design multi-target ligands for the treatment of Alzheimer's disease (AD), an approach that is moved by the knowledge that AD is a complex and multifactorial disease affecting many linked to pathological pathways. Accordingly, we have devoted efforts to develop multi-target ligands based on the chromone scaffold. As a result, a small library of chromone derivatives was synthesized and screened towards human cholinesterases and monoamine oxidases. Compounds 2-(dimethylamino)ethyl (E)-3-(4-oxo-2-(p-methylphenIcarbamoy1)-4H-chromen-6-yl)acrylate (9a) and 2-(dimethylamino)ethyl (E)-3-(4-oxo-3-(phenylcarbamoyl)-4H-chromen-6-yl)acrylate (23a) were identified as the most promising multi-target inhibitors of the series. Compound 9a acted as a potent, selective and bifunctional AChEI (IC50 = 0.21 mu M, K-i = 0.19 mu M) and displayed dual hMAO inhibitory activity (hMAO-A IC50 = 0.94 mu M, K-i = 0.057 mu M and hMAO-B IC50 = 3.81 mu M, K-i = 0.48 mu M). Compound 23a acted as a selective IMAO-B (IC50 = 0.63 mu M K-i = 0.34 mu M) while still displaying hChE inhibitory and bifunctional activity in the low micromolar range. Overall, these two compounds stand out as reversible multi-target inhibitors with favourable permeability, toxicological and drug-like profiles, thus being valid candidates for subsequent optimization and pre-clinical studies. (C) 2018 Published by Elsevier Masson SAS.

Abstract Monoamine oxidase B (MAO-B) is a validated drug target for Parkinson's disease. Chromone derivatives were identified as novel potent and reversible MAO-B inhibitors, and herewith we report on a crystallographic and biochemical analysis to investigate their inhibition mechanism. The crystal structures of human MAO B in complex with three chromone analogs bearing different substituents on the exocyclic aromatic ring (determined at 1.6-1.8 A resolution) showed that they all bind in the active site cavity of the protein with the chromone moiety located in front of the FAD cofactor. These inhibitors form two hydrogen bonds with Tyr435 and Cys172 and perfectly fit the hydrophobic flat active site of human MAO-B. This is reflected in their tight-binding mechanism of inhibition with IC, values of 55, 17, and 31 nM for N-(3',4'dimethylphenyl)-4-oxo-4H-chromene-3-carboxamide (3) (1), N-(3 'chloropheny1)-4-oxo-4H-chrom ene-3-carboxamide (2), and N-(3'-fluoropheny1)-4-oxo-4H-chromene-3-carboxamide respectively. These compounds were also 1000-fold more effective than L-deprenyl in reducing the cellular levels of reactive oxygen species (ROS).