Synthesis of phenylseleno sugars from epoxides and of α,β-unsaturated carbonyl derivatives for the study of their insecticidal activity

This work reports the synthesis of sugar epoxides and their derivatives obtained by reaction with the dianion of phenyl selenoacetic acid. Approaches to the introduction of α,β-unsaturated carbonyl units in pyranoid systems were investigated. Preparation of a protected D-glycero-hex-3-enepyranosid-2-ulose and of a D-erythro-hex-2-enono-1,5-lactone is described. Some of the synthesized compounds possess insecticidal activity against fruit flies, house flies, and white flies.Treaty of Windsor Programme, British Council, Ministério da Ciência e do Ensino Superiorinfo:eu-repo/semantics/publishedVersio

Capillary electrophoresis-mass spectrometry characterisation of secondary metabolites from the antihyperglycaemic plant Genista tenera

Genista tenera is endemic to the Portuguese island of Madeira, where an infusion of the aerial parts of the plant is used in folk medicine as an antidiabetic agent. Consequently the medicinal properties of the secondary metabolites of this plant have been the subject of an ongoing study. A recently reported LC-MS method using a 100 min separation allowed identification of five flavonoid components in an extract of the aerial parts of this plant. In order to obtain additional information on the range and complexity of the plant’s secondary metabolite components a CE-MS method has been developed and applied for the analysis of an extract of G. tenera. Twenty-six different components are distinguished in an analysis time of only 10 min. Results demonstrate that CE-MS/MS rapidly generates data complementary to those obtainable by LC-MS/MS and is particularly suited to the analysis of plant metabolites where concentration is not limiting.BBSRC, University of York, Treaty of Windsor Anglo-Portuguese joint research programme, Thermo Electron, Analytical Chemistry Trust Fund, Royal Society of Chemistry Analytical Division, Engineering and Physical Sciences Research Council (EPSRC)info:eu-repo/semantics/publishedVersio

New In Vitro studies on the bioprofile of Genista tenera antihyperglycemic extract

The inhibition of a-glucosidase and glucose-6-phosphatase, two enzymes involved in the carbohydrate metabolism, is an important target to control glycaemia on individuals with type 2 diabetes. In this work we report for the first time the inhibition of both enzymes by the antihyperglycemic n-butanol extract from Genista tenera (Fabaceae). This extract decreased a-glucosidase and glucose-6-phosphatase activities to 0.97 and 80.25 %, respectively, being more effective than acarbose, and phlorizin, the positive controls, which reduced enzymes activities only to 17.39 and 96.06 %. Once inflammation and oxidative stress are related to diabetic impairments, the anti-inflammatory activity of the extract was also evaluated, through its inhibitory activity over COX-1 enzyme (47.5 % inhibition). Moreover, after induction of oxidative stress by UV radiation, the viability of irradiated rat liver hepatoma cells exposed to the extract was significantly higher (67.82 %) than that promoted by ascorbic acid, the positive control (45.05 %). In addition, the stability of the extract under gastrointestinal conditions was evaluated by HPLC–DAD-ESI–MS/MS. Flavonoid diglycosides were identified as the main constituents of the extract, and no alterations in the chemical composition nor in the antioxidant activity were observed after in vitro digestion with artificial gastric and pancreatic juices.Fundação para a Ciência e a Tecnologia e Comissão Europeiainfo:eu-repo/semantics/publishedVersio

Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C–C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitors

Microwave-assisted synthesis of oxo-/thioxopyrimidines and tetrazoles linked to furanoses with D-xylo and D-ribo configuration, and to a D-galacto pyranose is reported and compared to conventional methods. Reaction of dialdofuranoses and dialdopyranoses with a b-keto ester and urea or thiourea under micro wave irradiation at 300 W gave in 10 min the target molecules containing the 2-oxo- or 2-thioxo-pyrimidine ring in high yield. The tetrazole-derived compounds were obtained in two steps by reaction of the formyl group with hydroxylamine hydrochloride, copper sulfate, triethylamine and dicyclohexylcarbodiimide to give an intermediate nitrile, which was then treated with sodium azide. The use of microwave irradiation in the latter step also resulted in a considerably shorter reaction time (10 min) compared to hours under conventional heating to obtain a complete starting materials conversion. Acetylcholinesterase inhibition ranged from 20% to 80% for compounds concentration of 100 lg/mL, demonstrating the potential of this family of compounds for the control of Alzheimer’s disease symptoms. Most of the compounds showed antioxidant activity in the b-carotene/linoleic acid assay, some of them exhibiting IC50 values in the same order of magnitude as those of gallic acid. The bioactive compounds did not show cytotoxic effects to human lymphocytes using the MTT method adapted for non-adherent cells, nor geno toxicity determined by the short-term in vitro chromosomal aberration assay.info:eu-repo/semantics/publishedVersio

Tuning the bioactivity of tensioactive deoxy glycosides to structure: antibacterial activity versus selective cholinesterase inhibition rationalized by molecular docking

New octyl/dodecyl 2,6-dideoxy-D-arabino-hexopyranosides have been synthesized by a simple but efficient methodology based on the reaction of glycals with alcohols catalysed by triphenylphosphane hydrobromide, deprotection, regioselective tosylation and reduction. Their surface-active properties were evaluated in terms of adsorption and aggregation parameters and compared with those of 2-deoxy-D-glycosides and 2,6-dideoxy-L-glycosides. Deoxygenation at the 6-position led to a decrease in the critical micelle concentration, and an increase in the adsorption efficiency (pC20) promoting aggregation more efficiently than adsorption. With regard to the antibacterial activity, dodecyl 2,6-dideoxy-α-L-arabino-hexopyranoside was the most active compound towards Bacillus anthracis (MIC 25 μM), whereas its enantiomer exhibited a MIC value of 50 μM. Both 2,6-dideoxy glycosides were active towards Bacillus cereus, Bacillus subtilis, Enterococcus faecalis and Listeria monocytogenes. In contrast, none of the 2-deoxy glycosides was significantly active. These results and the data on surface activity suggest that aggregation is a key issue for antimicrobial activity. Beyond infection, Alzheimer’s disease also threatens elderly populations. In the search for butyrylcholinesterase (BChE) selective inhibition, 2- deoxy glycosides were screened in vitro by using Ellman’s assay. Octyl 2-deoxy-α-D-glycoside was found to be a BChE selective inhibitor promoting competitive inhibition. Docking studies supported these results as they pinpoint the importance of the primary OH group in stabilizing the BChE inhibitor complex. A size-exclusion mechanism for inhibition has been proposed based on the fact that acetylcholinesterase (AChE) exhibits several bulky residues that hinder access to the active-site cavity. This work shows how the deoxygenation pattern, configuration and functionality of the anomeric centre can tune physical and surface properties as well as the bioactivity of these multifunctional and stereochemically rich molecules.FEDER e FCTinfo:eu-repo/semantics/publishedVersio

Discovery of N-methylpiperazinyl flavones as a novel class of compounds with therapeutic potential against Alzheimer’s disease : synthesis, binding affinity towards amyloid β oligomers (Aβo) and ability to disrupt Aβo-PrPC interactions

With no currently available disease-modifying drugs, Alzheimer’s disease is the most common type of dementia affecting over 47 million people worldwide. In light of the most recent discoveries placing the cellular prion protein (PrPC) as a key player in amyloid β oligomer (Aβo)-induced neurodegeneration, we investigated whether the neuroprotective potential of nature-inspired flavonoids against Aβ-promoted toxicity would translate into the ability to disrupt PrPC-Aβo interactions. Hence, we synthesized a small library of flavones and studied their binding affinity towards Aβo by STD-NMR. C-glucosyl flavones exhibited improved binding affinity with morpholine, thiomorpholine or N-methylpiperazine rings attached to the flavone skeleton in ring B para position. Moreover, a N-methylpiperazinyl flavone displayed suitable physicochemical properties and optimal water solubility even without the sugar moiety, and a high interaction with Aβo involving the whole flavone core. Its C-glucosyl derivative, was, however, the best compound to inhibit PrPC-Aβo interactions in a dose-dependent manner, with 41 % of inhibition capacity at 10 μM. The potential of C-glucosyl flavones and their aglycones as protein-protein interaction inhibitors able to tackle PrPC-Aβo interactions is here presented for the first time, and supports this class of compounds as new prototypes for further development in the treatment of Alzheimer’s disease

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters