Publications (13)32.71 Total impact
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Article: Electrochemical behavior of indolone-N-oxides: Relationship to structure and antiplasmodial activity.
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ABSTRACT: Indolone-N-oxides exert high parasiticidal activity at the nanomolar level in vitro against Plasmodium falciparum, the parasite responsible for malaria. The bioreductive character of these molecules was investigated using cyclic voltammetry and EPR spectroelectrochemistry to examine the relationship between electrochemical behavior and antimalarial activity and to understand their mechanisms of action. For all the compounds (37 compounds) studied, the voltammograms recorded in acetonitrile showed a well-defined and reversible redox couple followed by a second complicated electron transfer. The first reduction (-0.88V<E(1/2)<-0.50V vs. SCE) was attributed to the reduction of the N-oxide function to form a radical nitroxide anion. The second reduction (-1.65V<E(1/2)<-1.14V vs. SCE) was assigned to the reduction of the ketone function. By coupling electrochemistry with EPR spectroscopy, the EPR spectra confirmed the formation of the nitroxide anion radical. Moreover, the experiments demonstrated that a slow protonation occurs at the carbon of the nitrone function and not at the NO function. A relationship between electrochemical behavior and indolone-N-oxide structure can be established for compounds with R(1)=-OCH(3), R(2)=H, and electron-withdrawing substituents on the phenyl group at R(3). The results help in the design of new molecules with more potent in vivo antimalarial activity.Bioelectrochemistry (Amsterdam, Netherlands) 04/2012; 88:57-64. · 2.65 Impact Factor -
Article: Insights into the redox cycle of human quinone reductase 2.
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ABSTRACT: NRH:quinone oxidoreductase 2 (QR2) is a cytosolic enzyme that catalyzes the reduction of quinones, such as menadione and co-enzymes Q. With the aim of understanding better the mechanisms of action of QR2, we approached this enzyme catalysis via electron paramagnetic resonance (EPR) measurements of the by-products of the QR2 redox cycle. The variation in the production of oxidative species such as H(2)O(2), and subsequent hydroxyl radical generation, was measured during the course of QR2 activity under aerobic conditions and using pure human enzyme. The effects on the activity of the following were compared: (i) synthetic (N-benzyldihydronicotinamide, BNAH) or natural (nicotinamide riboside, NRH) co-substrates; (ii) synthetic (menadione) or natural (co-enzyme Q0, Q2) substrates; (iii) QR2 modulators and inhibitors (melatonin, resveratrol and S29434); (iv) a pro-drug activated via a redox cycle [CB1954, 5-(aziridin-1-yl)-2,4-dinitrobenzamide]. The results were also compared with those obtained with human QR1. The production of hydroxyl radicals is: (i) observed whatever the substrate/co-substrate used; ii) quenched by adding catalase; (iii) not observed with the specific QR2 inhibitor S29434; (iv) observed with the pro-drug CB1954. While QR2 produced free radicals with this pro-drug, QR1 gave no EPR signal showing the strong reducing capacity of QR2. In conclusion, EPR analysis of QR2 enzyme activity through free radical production enables modulators and effective inhibitors to be distinguished.Free radical research 08/2011; 45(10):1184-95. · 2.22 Impact Factor -
Article: Characterization of oxidative stress in Leishmaniasis-infected or LPS-stimulated macrophages using electrochemical impedance spectroscopy.
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ABSTRACT: The physiological changes caused by external stimuli can be employed as parameters to study pathogen infection in cells and the effect of drugs. Among analytical methods, impedance is potentially useful to give insight into cellular behavior by studying morphological changes, alterations in the physiological state, production of charged or redox species without interfering with in vitro cellular metabolism and labeling. The present work describes the use of electrochemical impedance spectroscopy to simply monitor by modeling impedance plots (Nyquist diagram) in appropriate equivalent circuit, the changes affecting murine macrophage cell line (RAW 264.7) in response to parasite infection by Leishmania amazonensis or to lipopolysaccharide (LPS) treatment. These results demonstrate the ability of electrochemical impedance spectroscopy to discriminate between two opposite cell responses associated to two different stimuli, one caused by the internalization of a parasite, and the other by activation by a bacterium component. Indeed, the study has allowed the characterization, from an electrical point of view, of the extra-cellular NO radical produced endogenously and in great quantities by the inducible form of NO-synthase in the case of LPS-stimulated macrophages. This production was not observed in the case of Leishmania-infected macrophages for which to survive and multiply, the parasite itself possesses mechanisms which may interfere with NO production. In this latest case, only the intracellular production of ROS was observed. To confirm these interpretations confocal microscopy analysis using the ROS (reactive oxygen species) fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate and electron paramagnetic resonance experiments using Fe(DETC)(2) as NO radical spin trap were carried out.Biosensors & bioelectronics 08/2010; 25(12):2566-72. · 5.43 Impact Factor -
Article: Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives
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ABSTRACT: A series of 66 new indolone-N-oxide derivatives was synthesized with three different methods. Compounds were evaluated for in vitro activity against CQ-sensitive (3D7), CQ-resistant (FcB1), and CQ and pyrimethamine cross-resistant (K1) strains of Plasmodium falciparum (P.f.), as well as for cytotoxic concentration (CC50) on MCF7 and KB human tumor cell lines. Compound 26 (5-methoxy-indolone-N-oxide analogue) had the most potent antiplasmodial activity in vitro (<3 nM on FcB1 and = 1.7 nM on 3D7) with a very satisfactory selectivity index (CC50 MCF7/IC50 FcB1: 14623; CC50 KB/IC50 3D7: 198823). In in vivo experiments, compound 1 (dioxymethylene derivatives of the indolone-N-oxide) showed the best antiplasmodial activity against Plasmodium berghei, 62% inhibition of the parasitaemia at 30 mg/kg/day.12/2009; -
Article: Synthesis and antiplasmodial activity of new indolone N-oxide derivatives.
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ABSTRACT: A series of 66 new indolone-N-oxide derivatives was synthesized with three different methods. Compounds were evaluated for in vitro activity against CQ-sensitive (3D7), CQ-resistant (FcB1), and CQ and pyrimethamine cross-resistant (K1) strains of Plasmodium falciparum (P.f.), as well as for cytotoxic concentration (CC(50)) on MCF7 and KB human tumor cell lines. Compound 26 (5-methoxy-indolone-N-oxide analogue) had the most potent antiplasmodial activity in vitro (<3 nM on FcB1 and = 1.7 nM on 3D7) with a very satisfactory selectivity index (CC(50) MCF7/IC(50) FcB1: 14623; CC(50) KB/IC(50) 3D7: 198823). In in vivo experiments, compound 1 (dioxymethylene derivatives of the indolone-N-oxide) showed the best antiplasmodial activity against Plasmodium berghei, 62% inhibition of the parasitaemia at 30 mg/kg/day.Journal of Medicinal Chemistry 12/2009; 53(2):699-714. · 4.80 Impact Factor -
Article: Ability of certain plant extracts traditionally used to treat ciguatera fish poisoning to inhibit nitric oxide production in RAW 264.7 macrophages.
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ABSTRACT: Ciguatera fish poisoning (CFP) is an intertropical ichthyosarcotoxism that manifests in complex assortment of symptoms in humans. Ciguatoxins (CTXs), issued from Gambierdicus spp., are causative agents of this intoxication. We have recently demonstrated that a Pacific CTX (P-CTX-1B) strongly modulated iNOS expression, leading to overproduction of nitric oxide (NO) in RAW 264.7 murine macrophage cells. NO produced in large amounts is involved in a wide range of pathophysiological processes. Many traditional remedies are commonly used in the Pacific against CFP. In this context, bioassay-guided screening was carried out to study NO inhibiting capacity of 28 selected plant extracts. We prepared aqueous extracts of plants used in New Caledonia in the treatment of CFP and screened their NO inhibitory activity in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Among 28 plants tested, Euphorbia hirta (Euphorbiaceae), Syzygium malaccense (Myrtaceae), Schinus terebenthifolius (Anacardiaceae), Punica granatum (Punicaceae), Cerbera manghas (Apocynaceae), Vitex trifolia (Labiateae) and Ximenia americana (Olacaceae) showed inhibitory activity, validating their use as traditional remedies in CFP, and the potential for use in the treatment of conditions accompanied by NO overproduction. These plants are promising candidates for further screening of their active compounds through activity-guided fractionation.Journal of ethnopharmacology 07/2009; 123(3):369-77. · 2.32 Impact Factor -
Article: Electrochemical impedance spectroscopy to study physiological changes affecting the red blood cell after invasion by malaria parasites.
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ABSTRACT: The malaria parasite, Plasmodium falciparum, invades human erythrocytes and induces dramatic changes in the host cell. The idea of this work was to use RBC modified electrode to perform electrochemical impedance spectroscopy (EIS) with the aim of monitoring physiological changes affecting the erythrocyte after invasion by the malaria parasite. Impedance cell-based devices are potentially useful to give insight into cellular behavior and to detect morphological changes. The modelling of impedance plots (Nyquist diagram) in equivalent circuit taking into account the presence of the cellular layer, allowed us pointing out specific events associated with the development of the parasite such as (i) strong changes in the host cell cytoplasm illustrated by changes in the film capacity, (ii) perturbation of the ionic composition of the host cell illustrated by changes in the film resistance, (iii) releasing of reducer (lactic acid or heme) and an enhanced oxygen consumption characterized by changes in the charge transfer resistance and in the Warburg coefficient characteristic of the redox species diffusion. These results show that the RBC-based device may help to analyze strategic events in the malaria parasite development constituting a new tool in antimalarial research.Biosensors & bioelectronics 01/2009; 24(8):2721-5. · 5.43 Impact Factor -
Article: Concentration and purification by magnetic separation of the erythrocytic stages of all human Plasmodium species.
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ABSTRACT: BACKGROUND: Parasite concentration methods facilitate molecular, biochemical and immunological research on the erythrocytic stages of Plasmodium. In this paper, an adaptation of magnetic MACS(R) columns for the purification of human Plasmodium species is presented. This method was useful for the concentration/purification of either schizonts or gametocytes. RESULTS AND CONCLUSIONS: The magnetic removal of non-parasitized red blood cells (in vivo and in vitro) using magnetic columns (MACS) was evaluated. This easy-to-use technique enriched schizonts and gametocytes from Plasmodium falciparum in vitro cultures with a very high degree of purity. In addition, all haemozoin-containing stages (schizonts and/or gametocytes) from the peripheral blood of infected patients could be concentrated using this method. This method is particularly useful for the concentration of non-falciparum species, which do not grow in culture and are otherwise difficult to obtain in large amounts.Malaria Journal 02/2008; 7:45. · 3.19 Impact Factor -
Article: Radical trapping properties of imidazolyl nitrones.
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ABSTRACT: The ability of ten imidazolyl nitrones to directly scavenge free radicals (R(*)) generated in polar ((*)OH, O(*)(2)(-), SO(*)(3)(-) cysteinyl, (*)CH(3)) or in apolar (CH(3)-(*)CH-CH(3)) media has been studied. When oxygen or sulfur-centered radicals are generated in polar media, EPR spectra are not or weakly observed with simple spectral features. Strong line intensities and more complicated spectra are observed with the isopropyl radical generated in an apolar medium. Intermediate results are obtained with (*)CH(3) generated in a polar medium. EPR demonstrates the ability of these nitrones to trap radicals to the nitrone C(alpha) atom (alpha radical adduct) and to the imidazol C(5) atom (5-radical adduct). Beside the nucleophilic addition of the radical to the C(alpha) atom, the EPR studies suggest a two-step mechanism for the overall reaction of R(*) attacking the imidazol core. The two steps seem to occur very fast with the (*)OH radical obtained in a polar medium and slower with the isopropyl radical prepared in benzene. In conclusion, imidazolyl nitrones present a high capacity to trap and stabilize carbon-centered radicals.Free Radical Research 02/2006; 40(1):11-20. · 2.88 Impact Factor -
Article: The use of polyethyleneimine for fabrication of potentiometric cholinesterase biosensors.
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ABSTRACT: Potentiometric biosensors based on butyrylcholinesterase are developed by co-reticulation of the enzyme with glutaraldehyde on an electropolymerized polyethyleneimine film at the electrode surface. The BuChE-electrode was tested as biochemical sensor for detection of an organophosphorus pesticide, trichlorfon in liquid, the detection being based on the enzyme inhibition. The enzyme electrode showed a detection limit for trichlorfon below 10(-7) M.Talanta 05/2002; 56(6):1015-20. · 3.79 Impact Factor -
Article: Antioxidant capacity of cotyledons and germs of soybean in relation to their isoflavone content
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ABSTRACT: The aim was to study the relationship between the antioxidant capacity and the isofla-vone content of soybean extracts depending on both geographic origin and cultivar. Soy-bean samples were obtained from two soybean seed parts, germ and cotyledon, from two geographical locations (L1, L2) and two cultivars (Queen, Imari), which gave 8 different samples. HPLC determination confirmed higher isoflavone content in germs than in coty-ledons, with higher contents in site L2, and in the Queen cultivar. The antioxidant capacity of soybean samples was determined with two methods, the 2,2-diphenyl-1-picrylhydrazyl scavenging assay and the oxygen radical absorbance capacity assay. The results obtained with both assays showed differences in antioxidant capacity between germ and cotyledon extracts, with a higher antioxidant activity of germ extracts. -
Article: Surface modification of p-Si by a polyethylenimine coating: influence of the surface pre-treatment. Application to a potentiometric transducer as pH sensor
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ABSTRACT: p-Si electrodes coated with linear polyethylenimine (L-PEI) allow the fabrication of a pH sensitive film for potentiometric transducers. The coating is realized in one step through the anodic oxidation of pure ethylenediamine (EDA) charged with 0.1 M LiCF 3 SO 3 (Lithium Triflate). Such an electrochemical procedure leads to the thickness control of the coating. The best silicon surface pre-treatment before any coating is obtained with potassium dichromate in sulfuric acid, which leads to OH-terminated p-Si. This pre-treatment allows a uniform thin coating. In this work, the thickness is 2.6 nm. The pH response is high and close to 50 mV per pH unit. # 2002 Elsevier Science B.V. All rights reserved. -
Article: Polyethyleneimine as a pH sensitive film for potentiometric transducers
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ABSTRACT: The anodic oxidation of ethylenediamine (EDA) leads to the formation of polyethyleneimine (PEI) as a pH sensitive thin film on conducting and semi-conducting electrode surfaces. The passivated electrodes exhibit a sub-nerstian response which depends strongly on the electrode material. In particular, the PEI-coated silicon electrodes present a linear pH sensitivity close to 50 mV per pH unit over a large pH range. This response could be fitted with the site-binding model applied to the acido-basic equilibrium of amino groups present at PEI/electrolyte interface.Materials Science and Engineering: C. 14:47-53.
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Institutions
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2006–2012
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Université Paul Sabatier - Toulouse 3
- Faculté des sciences pharmaceutiques
Toulouse, Midi-Pyrenees, France
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2011
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Université de Toulouse
Toulouse, Midi-Pyrenees, France
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