Synthesis of N-arylpyridinium salts bearing a nitrone spin trap as potential mitochondria-targeted antioxidants

The generation of excess reactive oxygen species (ROS) in mitochondria is responsible for much of the oxidative stress associated with ageing (aging), and mitochondrial dysfunction is part of the pathology of neurodegeneration and type 2 diabetes. Lipophilic pyridinium ions are known to accumulate in mitochondria and this paper describes a general route for the preparation of nitrone-containing N-arylpyridinium salts having a range of lipophilicities, as potential therapeutic antioxidants. The compatibility of nitrones with the Zincke reaction is the key to their synthesis. Their trapping of carbon-centred radicals and the EPR spectra of the resulting nitroxides are reported

Edgewise et forces directionnelles en denture mixte

L'auteur s'efforce, dans cet article, de développer les possibilités de la méthode edgewise dans les traitements des malocclusions en denture mixte. Il envisage une adaptation des forces directionnelles mises au point par la « Tweed Foundation for Orthodontic Research » sous la direction de MERRIFIELD et CROSS, dans les traitements précoces des classes II, division 1, classe II, division 2 et classe III

Les traitements de la classe II, division 2, de l'adolescent, avec ou sans extractions de prémolaires

L'auteur aborde les traitements des classes II, division 2, en envisageant les particularités dentaires, faciales et squelettiques qui définissent cette malocclusion. Il détaille deux types de traitement, l'un pour des cas nécessitant des extractions de prémolaires maxillaires et mandibulaires, l'autre envisagé pour des cas sans autres extractions que celles de dents très postérieures telles que les troisièmes molaires. La technique orthodontique décrite est inspirée de l'Edgewise de Tweed-Merrifield

Synthèse, études physico-chimiques et biologiques de nouveaux vecteurs amphiphiles porteurs d'antioxydants

AVIGNON-BU Centrale (840072102) / SudocSudocFranceF

Synthesis of cis-5-Trifluoromethylproline from L-Glutamic Acid

International audienceThe diastereoselective synthesis of cis-5-trifluoromethylproline (5-Tfm-Pro) from l-glutamic acid is described. 5-Tfm-Pro could be obtained through a seven-step linear sequence. Trifluoromethylation of the glutamic-derived ester or aldehyde and subsequent reduction of the cyclic imine are the key steps in the synthesis

Synthesis of acetylenic analogue of phenylalanine.

International audienceα -alkyl α-amino acids constitute an interesting class of non proteinogenic amino acids and are used to build new peptidic sequences with enhanced properties in various physiologically active peptides and proteins. The additional alkyl substituent could prevent the free rotation of the residue's side chain leading to unique folding when incorporated into peptides. Peptides containing quaternary α-amino acids also tend to have increased hydrophobicity, as well as an increased stability toward both chemical and metabolic decompositions. Unsaturated a-amino acids have turned out to be especially important building blocks for these studies due to the diverse reactivities of the multiple bonds and their ability to introduce biologically active functionalities. b,c-unsaturated amino acid derivatives have received crucial attention since they are important enzyme inhibitors. a-vinyl glycine is known to inhibit pyridoxal phosphate dependant enzymes in particular decarboxylase. Moreover,a-ethynyl amino acids are described such as potential suicide inhibitors of glutamic acid decarboxylase in particular ethynyl glycine is a well-known natural antibiotic and a suicide substrate for alanine racemase. Given this background, we herein report the synthesis of DL-ethynyl phenylalanine starting from DL-benzylserine in 9 steps

PBN derived amphiphilic spin-traps. II/Study of their antioxidant properties in biomimetic membranes.

International audienceThe work reported herein deals with the evaluation of the antioxidant properties of bitailed amphiphilic ␣-phenyl-N-tert-butylnitrone derivatives (BPBNs) towards oxidation of an unsaturated lipid, the 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLoPC). Oxidation was induced either by UV light irradiation or radical initiators, i.e. the water soluble AAPH and the Fenton reaction, and the antioxidant evaluation was carried out using two biomimetic systems, namely Langmuir monolayers and large unilamellar vesicles. Measurement of the molecular area and the membrane fluidity of pure nitrone monolayers before and after UV-irradiation demonstrated the better stability and antioxidant properties of B 17 PBN, the derivative with two C 17 H 35 alkyl chains, compared to its analogue B 11 PBN with two C 11 H 23 alkyl chains. At only 5% molar ratio of nitrone in mixed DLoPC/nitrone monolayers, a complete inhibition of the molecular area decrease was observed for B 17 PBN whereas B 11 PBN showed lower protection. The oxidation of mixed DLoPC/nitrones large unilamellar vesicles in the presence of free radicals arising from AAPH decomposition or Fenton reaction was assessed by measuring lipid conjugated dienes and thiobarbituric acid reactive substances on the whole series of nitrone, i.e. C 11-, C 13-, C 15-and C 17-based compounds. Compared to the saturated 1,2-dimyristoyl-sn-glycero-3-phosphocholine, all bitailed amphiphilic nitrones were able to decrease conjugated dienes and TBARS in both oxidative paradigms, demonstrating therefore antioxidant property. The inhibition of phospholipids oxidation was increased when increasing the concentration of nitrone with the two B 11 PBN and B 13 PBN derivatives exhibiting higher potency. This study underlines the importance in the choice of a model membrane system when evaluating the potency of antioxidants against lipid oxidation