22 research outputs found

    Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis

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    A convenient method for phosphorylation using trially phosphate

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    International audienceA direct method for the phosphorylation of alcohols, phenols, saccharides and nucleosides using triallyl phosphite is described. From primary or secondary alcohols, the corresponding diallyl-protected phosphorylated compounds are obtained in good to high yields. The method was found to be selective for primary alcohols and to be applicable to diverse simple and functionalized alcohols, including amino acids, carbohydrates and nucleosides

    Traitement par interféron alpha de sarcomes alvéolaires des tissus mous métastatiques à propos de deux cas

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    LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

    Mechanisms and synthetic modulators of AHL-dependent gene regulation.

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    International audienc

    The lipid peroxidation by-product 4-hydroxy-2-Nonenal (4-HNE) induces insulin resistance in skeletal

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    International audienceNumerous oxidants are produced as by-products of aerobic cell metabolism, and there is growing evidence that they play key roles in the pathogenesis of insulin resistance. Under conditions of oxidative stress, lipid peroxidation of ω6-polyunsaturated fatty acids leads to the production of 4-hydroxy-2-nonenal (4-HNE). Several lines of evidence suggest that 4-HNE could be involved in the pathophysiology of metabolic diseases; therefore, in this study we assessed the direct effects of 4-HNE on skeletal muscle insulin sensitivity. Gastrocnemius muscle and L6 muscle cells were treated with 4-HNE. Insulin signaling was measured by Western blotting and glucose uptake using 2-deoxy-d-[3H]glucose. Carbonyl stress, glutathione content, and oxidative stress were assessed as potential mechanisms leading to insulin resistance. Protection of cells was induced by pretreatment with 3H-1,2-dithiole-3-thione, N-acetyl-cysteine, aminoguanidine, or S-adenosyl-methionine. 4-HNE induced a time- and dose-dependent decrease in insulin signaling and insulin-induced glucose uptake in muscle. It induced a state of carbonyl stress through adduction of proteins as well as a depletion in reduced glutathione and production of radical oxygen species. A pharmacological increase in glutathione pools was achieved by 3H-1,2-dithiole-3-thione and protected the cells against all deleterious effects of 4-HNE; furthermore, N-acetylcysteine, aminoguanidine, and S-adenosylmethionine prevented 4-HNE noxious effects. 4-HNE can impair insulin action in muscle cells through oxidative stress and oxidative damage to proteins, eventually leading to insulin resistance. These deleterious effects can be prevented by pretreatment with antioxidants, scavengers, or an increase in intracellular glutathione pools. Use of such molecules could represent a novel strategy to combat insulin resistance and other oxidative stress-associated pathologies

    AHL-dependent quorum sensing inhibition: synthesis and biological evaluation of α-(N-alkyl-carboxamide)-γ-butyrolactones and α-(N-alkyl-sulfonamide)-γ-butyrolactones.

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    International audienceNew N-acylhomoserine lactone (AHL) analogues in which the amide function is replaced by a reverse-amide one have been studied as AHL QS modulators. The series of compounds consists of α-(N-alkyl-carboxamide)-γ-butyrolactones, α-(N-alkyl-sulfonamide)-γ-butyrolactones, and 2-(N-alkyl-carboxamide)-cyclopentanones and cyclopentanols. Most active compounds exhibited antagonist activities against LuxR reaching the 30 μM range
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