Browsing by Author "Rauter, A.P."
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- Capillary electrophoresis-mass spectrometry characterisation of secondary metabolites from the antihyperglycaemic plant Genista teneraPublication . Edwards, E.L.; Rodrigues, J.A.; Ferreira, J.; Goodall, D.M.; Rauter, A.P.; Justino, Jorge; Thomas-Oates, J.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.
- Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C–C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitorsPublication . Figueiredo, J.A.; Ismael, M.I.; Pinheiro, J.M.; Silva, A.M.S.; Justino, Jorge; Silva, Filipa V.M.; Goulart, Margarida; Mira, D.; Araújo, M.E.M.; Campoy, R.; Rauter, A.P.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.
- New In Vitro studies on the bioprofile of Genista tenera antihyperglycemic extractPublication . Batista, D.; Falé, P.L.; Serralheiro, M.L.; Araújo, M.E.; Madeira, P.J.A.; Borges, C.; Torgal, Isabel; Goulart, Margarida; Justino, Jorge; Martins, A.; Rauter, A.P.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.
- Synthesis of phenylseleno sugars from epoxides and of α,β-unsaturated carbonyl derivatives for the study of their insecticidal activityPublication . Rauter, A.P.; Canda, T.; Justino, Jorge; Ismael, M.I.; Figueiredo, J.A.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.
- Tuning the bioactivity of tensioactive deoxy glycosides to structure: antibacterial activity versus selective cholinesterase inhibition rationalized by molecular dockingPublication . Martins, A.; Santos, M.S.; Dias, C.; Serra, P.; Cachatra, V.; Pais, J.; Caio, J.; Teixeira, V.H.; Machuqueiro, M.; Silva, M.S.; Pelerito, A.; Justino, Jorge; Goulart, Margarida; Silva, Filipa; Rauter, A.P.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.