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Bolea I.,Autonomous University of Barcelona | Bolea I.,University of Florence | Colivicchi M.A.,University of Florence | Ballini C.,University of Florence | And 4 more authors.
CNS Neuroscience and Therapeutics | Year: 2014

Background: PF9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine] is an inhibitor of monoamine oxidase B (MAO-B), which has shown to possess neuroprotective properties in several in vitro and in vivo models of Parkinson's disease (PD). As there is evidence that excitotoxicity may be implicated in the pathophysiology of several neurodegenerative diseases, the aim of the present work was to investigate the effects of PF9601N in an acute in vivo model of excitotoxicity induced by the local administration of kainic acid during striatal microdialysis in adult rats. Methods: The basal and evoked release of neurotransmitters was monitored by HPLC analysis of microdialysate samples and tissue damage was evaluated histologically "ex vivo." Results: PF9601N (40 mg/kg, single i.p. administration) reduced the kainate-evoked release of glutamate and aspartate and increased taurine release, but it had no effect on the release of dopamine, DOPAC, and HVA. PF9601N pretreatment also resulted in a significant reduction in the kainate-induced astrocytosis, microgliosis, and apoptosis. Conclusions: The results suggest PF9601N to be a good candidate for the treatment of neurodegenerative diseases mediated by excitotoxicity. © 2014 John Wiley & Sons Ltd. Source

Samadi A.,Laboratorio Of Radicales Libres Y Quimica Computacional Iqog Csic | Soriano E.,Laboratorio Of Radicales Libres Y Quimica Computacional Iqog Csic | Revuelta J.,Laboratorio Of Radicales Libres Y Quimica Computacional Iqog Csic | Valderas C.,Laboratorio Of Radicales Libres Y Quimica Computacional Iqog Csic | And 11 more authors.
Bioorganic and Medicinal Chemistry | Year: 2011

The synthesis, structure, theoretical and experimental in vitro antioxidant properties using the DPPH, ORAC, and benzoic acid, as well as preliminary in vitro pharmacological activities of (Z)-α-aryl and heteroaryl N-alkyl-nitrones 6-15, 18, 19, 21, and 23, is reported. In the in vitro antioxidant activity, for the DPPH radical test, only nitrones bearing free phenol groups gave the best RSA (%) values, nitrones 13 and 14 showing the highest values in this assay. In the ORAC analysis, the most potent radical scavenger was nitrone indole 21, followed by the N-benzyl benzene-type nitrones 10 and 15. Interestingly enough, the archetypal nitrone 7 (PBN) gave a low RSA value (1.4%) in the DPPH test, or was inactive in the ORAC assay. Concerning the ability to scavenge the hydroxyl radical, all the nitrones studied proved active in this experiment, showing high values in the 94-97% range, the most potent being nitrone 14. The theoretical calculations for the prediction of the antioxidant power, and the potential of ionization confirm that nitrones 9 and 10 are among the best compounds in electron transfer processes, a result that is also in good agreement with the experimental values in the DPPH assay. The calculated energy values for the reaction of ROS (hydroxyl, peroxyl) with the nitrones predict that the most favourable adduct-spin will take place between nitrones 9, 10, and 21, a fact that would be in agreement with their experimentally observed scavenger ability. The in vitro pharmacological analysis showed that the neuroprotective profile of the target molecules was in general low, with values ranging from 0% to 18.7%, in human neuroblastoma cells stressed with a mixture of rotenone/oligomycin-A, being nitrones 18, and 6-8 the most potent, as they show values in the range 24-18.4%. © 2010 Elsevier Ltd. All rights reserved. Source

Sanchez-Patan F.,Institute Investigacion En Ciencias Of La Alimentacion Cial | Chioua M.,Laboratorio Of Radicales Libres Y Quimica Computacional Iqog Csic | Garrido I.,Institute Investigacion En Ciencias Of La Alimentacion Cial | Cueva C.,Institute Investigacion En Ciencias Of La Alimentacion Cial | And 5 more authors.
Journal of Agricultural and Food Chemistry | Year: 2011

The physiological significance of 5-(3′,4′-dihydroxyphenyl)- γ-valerolactone, an important metabolite derived from the catabolism of flavan-3-ols by gut microbiota, has been often overlooked due to the lack of the commercial standard. In the present work, this metabolite has been chemically synthesized, and its analytical parameters and antioxidant capacity have been determined in comparison to other chemical analogues [isomer 3-(3′,4′-dihydroxyphenyl)-δ-valerolactone and γ-valerolactone] and other structurally related compounds [(+)-catechin, (-)-epicatechin, and 3-(3,4-dihydroxyphenyl)-propionic acid]. The synthesized compound was also used to perform a targeted analysis in samples collected during the in vitro fermentation of a grape seed flavan-3-ol extract with human fecal microbiota from three healthy volunteers. The time-course formation of 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone revealed large interindividual differences among volunteers, with concentrations ranging from 3.31 to 77.54 μM at 10 h of fermentation. These results are further discussed in view of the scarce reports quantifying 5-(3′,4′-dihydroxyphenyl) -γ-valerolactone in in vitro fermentation studies, and pharmacokinetic and intervention studies. © 2011 American Chemical Society. Source

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