Pancreatic cancer (PDAC) lacks reliable diagnostic biomarkers and the search for new biomarkers represents an important challenge. Previous results looking at a small cohort of patients showed an increase in α-1-acid glycoprotein (AGP) fucosylation in advanced PDAC using N-glycan sequencing. Here, we have analysed AGP glycoforms in a larger cohort using several analytical techniques including mass spectrometry (MS), capillary zone electrophoresis (CZE) and enzyme-linked lectin assays (ELLAs) for determining AGP glycoforms which could be PDAC associated. AGP from 31 serum samples, including healthy controls (HC), chronic pancreatitis (ChrP) and PDAC patients, was purified by immunoaffinity chromatography. Stable isotope labelling of AGP released N-glycans and their analysis by zwitterionic hydrophilic interaction capillary liquid chromatography electrospray MS (μZIC-HILIC-ESI-MS) showed an increase in AGP fucosylated glycoforms in PDAC compared to ChrP and HC. By CZE-UV analysis, relative concentrations of some of the AGP isoforms were found significantly different compared to those in PDAC and HC. Finally, ELLAs using Aleuria aurantia lectin displayed a significant increase in AGP fucosylation, before and after AGP neuraminidase treatment, in advanced PDAC compared to ChrP and HC, respectively. Altogether, these results indicate that α1-3 fucosylated glycoforms of AGP are increased in PDAC and could be potentially regarded as a PDAC biomarker. © 2015 Elsevier B.V.

A tripartite cancer vaccine candidate, containing a quaternary amino acid (α-methylserine) in the most immunogenic domain of MUC1, has been synthesized and examined for antigenic properties in transgenic mice. The vaccine which is glycosylated with GalNAc at the unnatural amino acid, was capable of eliciting potent antibody responses recognizing both glycosylated and unglycosylated tumour-associated MUC1 peptides and native MUC1 antigen present on cancer cells. The peptide backbone of the novel vaccine presents the bioactive conformation in solution and is more resistant to enzymatic degradation than the natural counter part. In spite of these features, the immune response elicited by the unnatural vaccine was not improved compared to a vaccine candidate containing natural threonine. These observations were rationalized by conformational studies, indicating that the presentation and dynamics of the sugar moiety displayed by the MUC1 derivative play a critical role in immune recognition. It is clear that engineered MUC1-based vaccines bearing unnatural amino acids have to be able to emulate the conformational properties of the glycosidic linkage between the GalNAc and the threonine residues. The results described here will be helpful to the rational design of efficacious cancer vaccines. © The Royal Society of Chemistry 2016.

This article describes the toxicokinetics of perfluorooctane sulfonate (PFOS) in rabbits under low repeated dosing, equivalent to 0.085. μg/kg per day, and the observed differences between rabbits and chickens. The best fitting for both species was provided by a simple pseudo monocompartmental first-order kinetics model, regulated by two rates, and accounting for real elimination as well as binding of PFOS to non-exchangeable structures. Elimination was more rapid in rabbits, with a pseudo first-order dissipation half-life of 88 days compared to the 230 days observed for chickens. By contrast, the calculated assimilation efficiency for rabbits was almost 1, very close to full absorption, significantly higher than the 0.66 with confidence intervals of 0.64 and 0.68 observed for chickens. The results confirm a very different kinetics than that observed in single-dose experiments confirming clear dose-related differences in apparent elimination rates in rabbits, as previously described for humans and other mammals; suggesting the role of a capacity-limited saturable process resulting in different kinetic behaviours for PFOS in high dose versus environmentally relevant low dose exposure conditions. The model calculations confirmed that the measured maximum concentrations were still far from the steady state situation, and that the different kinetics between birds and mammals should may play a significant role in the biomagnifications assessment and potential exposure for humans and predators. For the same dose regime, the steady state concentration was estimated at about 36. μg PFOS/L serum for rabbits, slightly above one-half of the 65. μg PFOS/L serum estimated for chickens. The toxicokinetic parameters presented here can be used for higher-tier bioaccumulation estimations of PFOS in rabbits and chickens as starting point for human health exposure assessments and as surrogate values for modeling PFOS kinetics in wild mammals and bird in exposure assessment of predatory species. © 2015.

Glycosylation of alcohol derivatives with D-mannose and D-glucose derived methyl 1,2-orthobenzoates can be promoted by commercially available acid-washed 300 molecular sieves (AW-MS), which functions both as promoter and as a drying agent in an operationally simple process. In this manner, glycosides can be obtained in good to excellent yields at room temperature, reflux, or under microwave (MW) heating. The usefulness of the process has been shown with the preparation of some diterpene glycosides. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Carbohydrate derivatives are useful chiral building blocks for the enantiomerically pure compound synthesis of an ample variety of compounds. In this chapter, we present an outline of our recent research on the synthesis of unsaturated carbohydrates and their applications as intermediates for the preparation of peptide-scaffold hybrids, functionalized heterocycles, and alkaloids through the use of the Claisen and Overman rearrangements as well as the sequential intramolecular azide-alkene cycloaddition/nitrogen extrusion; as exemplified in the first total synthesis of the pyrrolizidine alkaloid amphorogynine C. © 2016 by John Wiley & Sons, Inc. All rights reserved.

Carbon materials such as activated carbons and graphitic materials and nanomaterials have been used for decades in heterogeneous catalysis as catalyst supports. The physical and chemical properties of these materials, such as their tunable porosity and surface chemistry, allow the anchoring and dispersion of the active phases, and make them suitable for application in many catalytic green processes. In this review, we summarize relevant applications and limitations of metal-supported carbons and nanocarbons in the synthesis of valuable products and the recent advances in this field. © 2016 The Royal Society of Chemistry.

Porous polymeric aromatic frameworks (PAFs) have high porosity and surface area, as well as high physicochemical stability; such characteristics are important in the design of heterogeneous catalysts with high catalytic efficiency and recyclability. This paper presents the synthesis, characterization, post-functionalization and catalytic performance of the resulting modified PAFs based on tetraphenyladamantane (PAFAd), tetraphenylmethane (PAFC) and 9,9′-spirobisfluorene (PAFspf) nodes. The PAFs were obtained by the Suzuki-Miyaura cross-coupling under microwave heating, and were sequentially reacted with 1-(chloromethoxy)octane and 1-mesityl-1H-imidazole or 2-(1H-imidazol-1-yl)pyridine to yield the corresponding imidazolium chloride derivative (PAF-Im) which readily formed stable N-heterocyclic carbene (NHC) iridium and ruthenium complexes (PAF-(NHC)Ir, PAF-(NHC)Ru). The materials were characterized by solid-state NMR spectroscopy, FTIR spectroscopy, and textural analysis. The PAF-(NHC)M materials display excellent catalytic performance in the N-alkylation of amines with alcohols and transfer hydrogenation of ketones over multiple catalytic cycles. © 2016 The Royal Society of Chemistry.

The quantitative extraction and subsequent purification of trace contaminants from (semi-)solid environmental and food matrices of regular size (that is, a few grams) is still recognized as a challenging task, typically accomplished through relatively complex off-line multistep treatment procedures. When these conventional sample preparation procedures are applied to the treatment of size-limited samples (of less than 1 g), the difficulties increase. This review discusses the different analytical strategies that can be adopted to overcome (or at least reduce) these difficulties when chromatographic techniques are involved for final instrumental determination. © 2016 Advanstar Communications Inc. All rights reserved.

Aminoglycosides are especially useful for the treatment of hospital-acquired infections. The main problem for the application of these antibiotics is the presence of bacterial resistance enzymes, in particular, nucleotidyltransferases (ANTs). These enzymes catalyze the transfer of an adenylyl group from the MgATP complex to different positions of the antibiotic. To understand the mechanisms that lead to antibiotic inactivation, we have performed a comprehensive experimental analysis of one of those enzymes. The 6-O- nucleotidyltransferase enzyme (ANT(6)) from Bacillus subtilis was cloned, overexpressed and purified in E. coli. The kinetic parameters revealed a narrow specificity of the ANT(6) for MgATP/streptomycin as substrates. The binding epitope of the streptomycin recognized by the ANT(6) is the streptidine moiety. Therefore, the use of streptidine as a decoy acceptor allows the recovery of the antibiotic activity of streptomycin E. coli cells that are overexpressing the ANT(6). © 2016 The Royal Society of Chemistry.

Although qualitative strategies based on direct injection mass spectrometry (DiMS) have recently emerged as an alternative for the rapid classification of food samples, the potential of these approaches in quantitative tasks has scarcely been addressed to date. In this paper, the applicability of different multivariate regression procedures to data collected by DiMS from simulated mixtures has been evaluated. The most relevant factors affecting quantitation, such as random noise, the number of calibration samples, type of validation, mixture complexity and similarity of mass spectra, were also considered and comprehensively discussed. Based on the conclusions drawn from simulated data, and as an example of application, experimental mass spectral fingerprints collected by direct thermal desorption coupled to mass spectrometry were used for the quantitation of major volatiles in Thymus zygis subsp. zygis chemotypes. The results obtained, validated with the direct thermal desorption coupled to gas chromatography-mass spectrometry method here used as a reference, show the potential of DiMS approaches for the fast and precise quantitative profiling of volatiles in foods. © 2016 The Author(s) Published by the Royal Society. All rights reserved.

The antioxidant and antifungal (antiyeast) properties of mango (Mangifera indica) peel and seed by-products were investigated. Nine extracts were obtained using three cultivars and two extraction methods. Significant differences between cultivars and extraction methods were detected in their bioactive compounds and antioxidant activity. The antifungal property was determined using agar diffusion and broth micro-dilution assays against 18 yeast species of the genera Candida, Dekkera, Hanseniaspora, Lodderomyces, Metschnikowia, Pichia, Schizosaccharomyces, Saccharomycodes and Zygosaccharomyces. All mango extracts showed antifungal activity. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) values were lower for seed than for peel extracts. MICs and MFCs ranged from values <0.1 to 5 and 5 to >30 mgGAE/mL, respectively. The multivariate analysis showed a relationship between antifungal activity, the capacity to inhibit lipid peroxidation and total phenol content. These properties were associated with high levels of proanthocyanidins, gallates and gallotannins in the extracts. © 2015 Informa UK Limited, trading as Taylor & Francis Group.

Therapeutic interventions on pathological processes involved in the ischemic cascade, such as oxidative stress, neuroinflammation, excitotoxicity and/or apoptosis, are of urgent need for stroke treatment. Melatonin regulates a large number of physiological actions and its beneficial properties have been reported. The aim of this study was to investigate whether melatonin mediates neuroprotection in rat hippocampal slices subjected to oxygen-glucose-deprivation (OGD) and glutamate excitotoxicity. Thus, we describe here that melatonin significantly reduced the amount of lactate dehydrogenase released in the OGD-treated slices, reverted neuronal injury caused by OGD-reoxygenation in CA1 and CA3 hippocampal regions, restored the reduction of GSH content of the hippocampal slices induced by OGD, and diminished the oxidative stress produced in the reoxygenation period. Furthermore, melatonin afforded maximum protection against glutamate-induced toxicity and reversed the glutamate released almost basal levels, at 10 and 30 μM concentration, respectively. Consequently, we propose that melatonin might strongly and positively influence the outcome of brain ischemia/reperfusion. © 2016 Elsevier B.V.

Abstract: New heterocyclic privileged medicinal scaffolds involving 4H-pyran, 1,4-dihydropyridine, quinazoline, and 2-aminochromene bearing a (benz)imidazole unit were prepared in good to excellent yields, and evaluated for their in vitro hepatotoxicity on HepG2 cells and antioxidant activity using DPPH radical-scavenging assay. From these results, 2-amino-4-(1-methyl-1H-imidazol-2-yl)-4H-benzo[h]chromene-3-carbonitrile has been identified as a racemic, readily available imidazole derivative, significantly less hepatotoxic than tacrine at 100 μM concentration. One compound was found to be a potent antioxidant agent. The catalytic effect of the 1-methylimidazole unit, in the synthesis of some heterocycle, was also demonstrated. Crystal X-ray structures are reported for six compounds. Graphical abstract: [Figure not available: see fulltext.] © 2016, Springer-Verlag Wien.

Sulfinyl trichloroacetamides are readily obtained in excellent yields through a highly stereoselective Overman rearrangement. Related bis-allylic substrates lead to amido 2-sulfinyl butadiene derivatives in excellent yields, with total chemo- and diastereoselectivity. These amido dienyl sulfoxides undergo highly selective Diels-Alder cycloadditions with N-phenylmaleimide with remarkable stereocontrol by the sulfoxide moiety. © 2016 American Chemical Society.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers and have been detected ubiquitously in the remote atmosphere. Fourteen OPEs were analyzed in 115 aerosol phase samples collected from the tropical and subtropical Atlantic, Pacific, and Indian Oceans during the MALASPINA circumnavigation campaign. OPEs were detected in all samples with concentrations ranging from 360 to 4400 pg m -3 for the sum of compounds. No clear concentration trends were found between the Northern and Southern hemispheres. The pattern was generally dominated by tris(1-chloro-2-propyl) phosphate (TCPP), although tri-n-butyl phosphate (TnBP) had a predominant role in samples close to continents and in those influenced by air masses originating in continents. The dry deposition fluxes of aerosol phase Σ 14 OPE ranged from 4 to 140 ng m -2 d -1 . An estimation of the OPE gas phase concentration and gross absorption fluxes by using three different sets of physical chemical properties suggested that the atmosphere-ocean diffusive exchange of OPEs could be 2-3 orders of magnitude larger than dry deposition. The associated organic phosphorus inputs coming from diffusive OPE fluxes were estimated to potentially trigger up to 1.0\% of the reported primary production in the most oligotrophic oceanic regions. However, the uncertainty associated with these calculations is high and mostly driven by the uncertainty of the physical chemical properties of OPEs. Further constraints of the physical chemical properties and fluxes of OPEs are urgently needed, in order to estimate their environmental fate and relevance as a diffusive source of new organic phosphorus to the ocean. (Figure Presented). © 2016 American Chemical Society.

The complex nature of Alzheimer's disease (AD) has prompted the design of Multi-Target-Directed Ligands (MTDL) able to bind to diverse biochemical targets involved in the progress and development of the disease. In this context, we have designed a number of MTD propargylamines (MTDP) showing antioxidant, anti-beta-amyloid, anti-inflammatory, as well as cholinesterase and monoamine oxidase (MAO) inhibition capacities. Here, we describe these properties in the MTDL ASS234, our lead-compound ready to enter in pre-clinical studies for AD, as a new multipotent, permeable cholinesterase/monoamine oxidase inhibitor, able to inhibit Aß-aggregation, and possessing antioxidant and neuroprotective properties. © 2016 Marco-Contelles, Unzeta, Bolea, Esteban, Ramsay, Romero, Martínez-Murillo, Carreiras and Ismaili.

We report on steady-state and picosecond time-resolved emission studies of (E)-2-(2'-hydroxybenzyliden)amino-4-nitrophenol (HBA-4NP) interacting with MCM41, Al-MCM41 and SBA15. In these materials, the molecule shows spectral changes, with a broadening and shifts of absorption and emission bands, which depend on the concentration used in the preparation of the samples, indicating the aggregates formation. These caged monomers (M), H- and J-aggregates are in enol form at S0 and in keto one at S1, as a result of an excited-state intramolecular proton transfer (ESIPT) reaction. The K lifetime of the caged M is longer (3 ns) than the observed in solution (14 ps), due to the confinement effect on the radiationless pathways. The K lifetimes of J- and H-aggregates are 600 and 100 ps, respectively, and their populations and stability depend on pore size and chemical composition (in terms of Brönsted acidity) of the host. For MCM41 and Al-MCM41 ones, the formation of H- and J-aggregates is higher than using SBA15. This is due to a better encapsulation by the formers (85-95\% MCM41/Al-MCM41 vs 60\% SBA15). Doping MCM41 by Al allows more J-aggregates as result of strong interaction between the guest molecules and the Al-MCM41 framework. Thus, modulating the topological and structural properties of the mesoporous material leads to the formation of different encapsulated species, which could be of great interest to design nanophotonics devices based on this kind of materials. © 2015 Elsevier Inc. All rights reserved.

Two series of thiazolium bis(trifluoromethylsulfonyl)imide [NTf2] room temperature ionic liquids (RTILs) functionalized with oligo(oxyethylene)-chains have been synthesized in multigram scale and characterized. Their thermal properties and conductivity values have been determined. The increase in the number and length of the oligo(oxyethylene)-chains attached to the thiazolium ring resulted in lower values of ionic conductivity. © 2016 Elsevier Ltd

Pressurized liquid extraction of Aglaonema sp. iminosugars has been optimized. A single cycle under optimal conditions (80 mg, 100 °C, 2 min) was enough to extract ≥96\% of most iminosugars. Further incubation with Saccharomyces cerevisiae for 5 h removed coextracted interfering low molecular weight carbohydrates from extracts of different Aglaonema cultivars. A complete characterization of these extracts was carried out by gas chromatography-mass spectrometry: three iminosugars were tentatively identified for the first time; α-homonojirimycin and 2,5-dideoxy-2,5-imino-d-mannitol were the major iminosugars determined. α-Glucosidase inhibition activity, cell viability and thermal stability of Aglaonema extracts were also evaluated. Extracts with IC50 for α-glucosidase activity in the 0.010-0.079 mg mL-1 range showed no decrease of Caco-2 cell viability at concentrations lower than 125 μg mL-1 and were stable at 50 °C for 30 days. These results highlight the potential of Aglaonema extracts as a source of bioactives to be used as functional ingredients. © 2016 Elsevier Ltd. All rights reserved.

Microwave assisted extraction (MAE) and pressurized liquid extraction (PLE) methods using water as solvent have been optimized by means of a Box-Behnken and 3 2 composite experimental designs, respectively, for the effective extraction of bioactive carbohydrates (inositols and inulin) from artichoke (Cynara scolymus L.) external bracts. MAE at 60 °C for 3 min of 0.3 g of sample allowed the extraction of slightly higher concentrations of inositol than PLE at 75 °C for 26.7 min (11.6 mg/g dry sample vs. 7.6 mg/g dry sample). On the contrary, under these conditions, higher concentrations of inulin were extracted with the latter technique (185.4 mg/g vs. 96.4 mg/g dry sample), considering two successive extraction cycles for both techniques. Both methodologies can be considered appropriate for the simultaneous extraction of these bioactive carbohydrates from this particular industrial by-product. To the best of our knowledge this is the first time that these techniques are applied for this purpose. © 2015 Elsevier Ltd.