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Plant resistance inducers are among the most promising alternatives to develop sustainable crop protection. Here, we examined the ability of saccharin, a metabolite derived from probenazole, to protect wheat against Zymoseptoria tritici, the most frequently occurring and damaging foliar pathogen on this crop. The experiments were performed in the greenhouse by treating seedlings of the wheat cultivar ‘Alixan’ with 15 mM of saccharin 2 days before challenge inoculation with the Z. tritici pathogenic strain T02596. Foliar application of saccharin resulted in 77% lower disease severity than in nontreated control plants. In vitro and in planta assays showed that saccharin did not exhibit any direct antifungal effect on spore germination or hyphal growth. Molecular investigations from 2 to 7 days posttreatment (dpt) revealed that saccharin treatment upregulates the expression of genes encoding for lipoxygenase (LOX) at all sampled time points and pathogenesis-related protein 1 (PR1) at 7 dpt, in both noninfectious and infectious contexts, as well as peroxidase (POX2) in noninfectious conditions. However, saccharin did not induce significant change in the expression of PAL gene encoding for phenylalanine ammonia-lyase. Our findings report for the first time the potential of saccharin to confer protection in wheat against Z. tritici through an elicitation and priming of LOX and PR gene-related defense pathways. Additional investigations would provide a better deciphering of defense mechanisms activated by this molecule in wheat against Z. tritici.
Samara Mejri; Maryline Magnin-Robert; Beatrice Randoux; Alina Ghinet; Patrice Halama; Ali Siah; Philippe Reignault. Saccharin Provides Protection and Activates Defense Mechanisms in Wheat Against the Hemibiotrophic Pathogen Zymoseptoria tritici. Plant Disease 2021, 105, 780 -786.
AMA StyleSamara Mejri, Maryline Magnin-Robert, Beatrice Randoux, Alina Ghinet, Patrice Halama, Ali Siah, Philippe Reignault. Saccharin Provides Protection and Activates Defense Mechanisms in Wheat Against the Hemibiotrophic Pathogen Zymoseptoria tritici. Plant Disease. 2021; 105 (4):780-786.
Chicago/Turabian StyleSamara Mejri; Maryline Magnin-Robert; Beatrice Randoux; Alina Ghinet; Patrice Halama; Ali Siah; Philippe Reignault. 2021. "Saccharin Provides Protection and Activates Defense Mechanisms in Wheat Against the Hemibiotrophic Pathogen Zymoseptoria tritici." Plant Disease 105, no. 4: 780-786.
Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor-bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a strategy that may be active against NSCLC.
Laetitia Douguet; Serena Janho Dit Hreich; Jonathan Benzaquen; Laetitia Seguin; Thierry Juhel; Xavier Dezitter; Christophe Duranton; Bernhard Ryffel; Jean Kanellopoulos; Cecile Delarasse; Nicolas Renault; Christophe Furman; Germain Homerin; Chloé Féral; Julien Cherfils-Vicini; Régis Millet; Sahil Adriouch; Alina Ghinet; Paul Hofman; Valérie Vouret-Craviari. A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy. Nature Communications 2021, 12, 1 -17.
AMA StyleLaetitia Douguet, Serena Janho Dit Hreich, Jonathan Benzaquen, Laetitia Seguin, Thierry Juhel, Xavier Dezitter, Christophe Duranton, Bernhard Ryffel, Jean Kanellopoulos, Cecile Delarasse, Nicolas Renault, Christophe Furman, Germain Homerin, Chloé Féral, Julien Cherfils-Vicini, Régis Millet, Sahil Adriouch, Alina Ghinet, Paul Hofman, Valérie Vouret-Craviari. A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy. Nature Communications. 2021; 12 (1):1-17.
Chicago/Turabian StyleLaetitia Douguet; Serena Janho Dit Hreich; Jonathan Benzaquen; Laetitia Seguin; Thierry Juhel; Xavier Dezitter; Christophe Duranton; Bernhard Ryffel; Jean Kanellopoulos; Cecile Delarasse; Nicolas Renault; Christophe Furman; Germain Homerin; Chloé Féral; Julien Cherfils-Vicini; Régis Millet; Sahil Adriouch; Alina Ghinet; Paul Hofman; Valérie Vouret-Craviari. 2021. "A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy." Nature Communications 12, no. 1: 1-17.
Based on previously reported chiral separation of free amino-acids (AAs) using packed-column supercritical fluid chromatography (pSFC), it was desirable to investigate parameters influencing the response of evaporative light scattering detector (ELSD). The effect of several parameters, such as SFC conditions (outlet pressure, temperature and flow rate) and ELSD settings (drift tube temperature of nebulisation and nebulizer gas pressure) on the sensitivity (response) of ELSD have been studied. Based on optimization an outlet pressure of 170 bar, a temperature of 40 °C and a flow rate of 3 mL/min were chosen, and a drift tube temperature of 60 °C and a nebulizer gas pressure of 3.0 bar were found to be optimal. Limits of detection (LOD) and limits of quantification (LOQ) were determined for studied amino acids (AAs) and were found to be lower than values determined without optimization. The enantiomeric elution order was also determined for leucine, phenylalanine, isoleucine, valine, carnitine and histidine by the injection of the L-AAs in the above-mentioned optimized conditions. The L-enantiomers eluted first for four out of the six AAs studied. Conclusions on the influence of the screened variables on ELSD sensitivity and recommendations for AAs analytical studies in SFC are given.
Germain Homerin; Alina Ghinet; Adrian Sorin Nica; Bezhan Chankvetadze; Emmanuelle Lipka. Optimization of Detection of Native Amino Acids with Evaporative Light Scattering Detector in Chiral Supercritical Fluid Chromatography. Chromatographia 2021, 84, 179 -185.
AMA StyleGermain Homerin, Alina Ghinet, Adrian Sorin Nica, Bezhan Chankvetadze, Emmanuelle Lipka. Optimization of Detection of Native Amino Acids with Evaporative Light Scattering Detector in Chiral Supercritical Fluid Chromatography. Chromatographia. 2021; 84 (2):179-185.
Chicago/Turabian StyleGermain Homerin; Alina Ghinet; Adrian Sorin Nica; Bezhan Chankvetadze; Emmanuelle Lipka. 2021. "Optimization of Detection of Native Amino Acids with Evaporative Light Scattering Detector in Chiral Supercritical Fluid Chromatography." Chromatographia 84, no. 2: 179-185.
The conception of two biosourced catalysts (biocatalysts) using stems of miscanthus from the first part of this study are described herein. The temperature and the process used to extract metals from plant as mixture of Lewis acids were investigated in detail and proved to be essential in the design of the biosourced catalysts and their catalytic efficiency. One part of the crude mixture of Lewis acids extracted from the aerial parts of miscanthus plants was used without further treatment as a homogeneous biocatalyst (M1), and the other part was supported on montmorillonite K10 to provide a heterogeneous biocatalyst (MM1). M1 and MM1 were next tested in the synthesis of moclobemide (main ingredient of a drug used to treat depression) and led to excellent yield. Additional comparative experiments with different commercial metallic salts (NaCl, KCl, CaCl2, MgCl2, CuCl2, ZnCl2, FeCl2, FeCl3, MnCl2, and AlCl3) and their mixtures were carried out and underlined the importance of the multimetallic synergy on catalytic activity. Finally, a comparison of this new synthetic method assisted by the biosourced catalyst with the previously described procedures to access moclobemide was realized by calculating their green chemistry metrics. This study revealed that the use of the biosourced catalyst led to one of the greenest synthetic methods described today to produce moclobemide.
Théo Guérin; Alina Ghinet; Christophe Waterlot. Toward a New Way for the Valorization of Miscanthus Biomass Produced on Metal-Contaminated Soils Part 2: Miscanthus-Based Biosourced Catalyst: Design, Preparation, and Catalytic Efficiency in the Synthesis of Moclobemide. Sustainability 2020, 13, 34 .
AMA StyleThéo Guérin, Alina Ghinet, Christophe Waterlot. Toward a New Way for the Valorization of Miscanthus Biomass Produced on Metal-Contaminated Soils Part 2: Miscanthus-Based Biosourced Catalyst: Design, Preparation, and Catalytic Efficiency in the Synthesis of Moclobemide. Sustainability. 2020; 13 (1):34.
Chicago/Turabian StyleThéo Guérin; Alina Ghinet; Christophe Waterlot. 2020. "Toward a New Way for the Valorization of Miscanthus Biomass Produced on Metal-Contaminated Soils Part 2: Miscanthus-Based Biosourced Catalyst: Design, Preparation, and Catalytic Efficiency in the Synthesis of Moclobemide." Sustainability 13, no. 1: 34.
Lolium perenne L., a common plant perennial ryegrass from Europe, northern Africa and Asia, was selected to produce biomass under field conditions. The biomass of this nonfood crop was from a highly contaminated agricultural soil by potentially toxic metals (Cd, Pb and Zn) with the aim of maintaining the agricultural vocation of these soils. In this perspective and in view of the metal concentration (Cd, Pb, Zn, macro- and micro-nutrients), the biomass of ryegrass was considered as a bio 'ore' resource and was used as the starting material for the preparation of contemporary biosourced catalysts. The heterogeneous catalyst from the current work was successfully used in the synthesis of Moclobemide, used to treat anxiety and major depressive episodes. Through this original approach, Moclobemide was synthesized in one step, in 80% yield under solvent-free conditions. GRAPHICAL ABSTRACT
Marie Hechelski; Christophe Waterlot; Pierrick Dufrénoy; Brice Louvel; Adam Daïch; Alina Ghinet. Biomass of ryegrass from field experiments: toward a cost-effective and efficient biosourced catalyst for the synthesis of Moclobemide. Green Chemistry Letters and Reviews 2020, 14, 15 -22.
AMA StyleMarie Hechelski, Christophe Waterlot, Pierrick Dufrénoy, Brice Louvel, Adam Daïch, Alina Ghinet. Biomass of ryegrass from field experiments: toward a cost-effective and efficient biosourced catalyst for the synthesis of Moclobemide. Green Chemistry Letters and Reviews. 2020; 14 (1):15-22.
Chicago/Turabian StyleMarie Hechelski; Christophe Waterlot; Pierrick Dufrénoy; Brice Louvel; Adam Daïch; Alina Ghinet. 2020. "Biomass of ryegrass from field experiments: toward a cost-effective and efficient biosourced catalyst for the synthesis of Moclobemide." Green Chemistry Letters and Reviews 14, no. 1: 15-22.
Heme’s interaction with toll‐like receptor 4 (TLR4) does not fully explain the pro‐inflammatory properties of this hemoglobin‐derived molecule during intravascular hemolysis. The receptor for advanced glycation end‐products (RAGE) shares many features with TLR4 such as common ligands and pro‐inflammatory, ‐thrombotic and ‐oxidative signaling pathways, prompting us to study its involvement as a heme sensor. Stable RAGE‐heme complexes with micromolar affinity were detected as heme‐mediated RAGE oligomerization. The heme binding site was located in the V domain of RAGE. This interaction was Fe3+‐dependent and competitive with carboxymethyllysine, another RAGE ligand. We confirmed a strong basal gene expression of RAGE in mouse lungs. After intraperitoneal heme injection, pulmonary TNFα, IL1β and tissue factor gene expression levels increased in WT mice but were significantly lower in their RAGE‐/‐ littermates. This may be related to the lower activation of ERK1/2 and Akt observed in the lungs of heme‐treated, RAGE‐/‐ mice. Overall, heme binds to RAGE with micromolar affinity and could promote pro‐inflammatory and pro‐thrombotic signaling in vivo, suggesting that this interaction could be implicated in heme overload conditions.
Olivia May; Laure Yatime; Nicolas S. Merle; Florian Delguste; Mike Howsam; Marie V. Daugan; Charles Paul‐Constant; Muriel Billamboz; Alina Ghinet; Steve Lancel; Jordan D. Dimitrov; Eric Boulanger; Lubka T. Roumenina; Marie Frimat. The receptor for advanced glycation end products is a sensor for cell‐free heme. The FEBS Journal 2020, 288, 3448 -3464.
AMA StyleOlivia May, Laure Yatime, Nicolas S. Merle, Florian Delguste, Mike Howsam, Marie V. Daugan, Charles Paul‐Constant, Muriel Billamboz, Alina Ghinet, Steve Lancel, Jordan D. Dimitrov, Eric Boulanger, Lubka T. Roumenina, Marie Frimat. The receptor for advanced glycation end products is a sensor for cell‐free heme. The FEBS Journal. 2020; 288 (11):3448-3464.
Chicago/Turabian StyleOlivia May; Laure Yatime; Nicolas S. Merle; Florian Delguste; Mike Howsam; Marie V. Daugan; Charles Paul‐Constant; Muriel Billamboz; Alina Ghinet; Steve Lancel; Jordan D. Dimitrov; Eric Boulanger; Lubka T. Roumenina; Marie Frimat. 2020. "The receptor for advanced glycation end products is a sensor for cell‐free heme." The FEBS Journal 288, no. 11: 3448-3464.
Gina-Mirabela Dumitriu; Elena Bîcu; Benoît Rigo; Ján Moncol; Adam Daïch; Alina Ghinet. In-depth examination of the pterolactams behaviour in Lewis/Brönsted acid catalysis environment: Total isolation of the reaction products. Arkivoc 2020, 2020, 94 -114.
AMA StyleGina-Mirabela Dumitriu, Elena Bîcu, Benoît Rigo, Ján Moncol, Adam Daïch, Alina Ghinet. In-depth examination of the pterolactams behaviour in Lewis/Brönsted acid catalysis environment: Total isolation of the reaction products. Arkivoc. 2020; 2020 (8):94-114.
Chicago/Turabian StyleGina-Mirabela Dumitriu; Elena Bîcu; Benoît Rigo; Ján Moncol; Adam Daïch; Alina Ghinet. 2020. "In-depth examination of the pterolactams behaviour in Lewis/Brönsted acid catalysis environment: Total isolation of the reaction products." Arkivoc 2020, no. 8: 94-114.
Dihydro‐1,4‐thiazine skeletons bearing olefin fragment at their α‐position were prepared through a robust Pd(OAc)2–catalysed Fujiwara‐Moritani type reaction via C–H alkenylation with olefins. This approach is selective, generalizable to a wide range of olefins and requires only 1 eq. of Ag2CO3 without the need of co‐oxidant. The C–H bond activation proved to be strongly dependent on the olefin’s substitution while unfused dihydro‐1,4‐thiazines seemed to be affected by the oxidation state of the sulfur atom. The utility of olefins obtained was demonstrated by their implication in the dipolar cycloaddition reaction with a non‐stabilized azomethine ylide.
Fanny Danton; Riham Najjar; Mohamed Othman; Ata Martin Lawson; Ján Moncol; Alina Ghinet; Benoît Rigo; Hassan Oulyadi; Adam Daïch. Site‐Selective Pd‐Catalysed Fujiwara‐Moritani type Reaction of N,S ‐Heterocyclic Systems with Olefins. Advanced Synthesis & Catalysis 2020, 363, 1088 -1095.
AMA StyleFanny Danton, Riham Najjar, Mohamed Othman, Ata Martin Lawson, Ján Moncol, Alina Ghinet, Benoît Rigo, Hassan Oulyadi, Adam Daïch. Site‐Selective Pd‐Catalysed Fujiwara‐Moritani type Reaction of N,S ‐Heterocyclic Systems with Olefins. Advanced Synthesis & Catalysis. 2020; 363 (4):1088-1095.
Chicago/Turabian StyleFanny Danton; Riham Najjar; Mohamed Othman; Ata Martin Lawson; Ján Moncol; Alina Ghinet; Benoît Rigo; Hassan Oulyadi; Adam Daïch. 2020. "Site‐Selective Pd‐Catalysed Fujiwara‐Moritani type Reaction of N,S ‐Heterocyclic Systems with Olefins." Advanced Synthesis & Catalysis 363, no. 4: 1088-1095.
The effects of P-fertilizers (mono- and di-calcium phosphates) on the bioavailability of metals and nutrients in leaves and stems of Miscanthus × giganteus were studied in mesocosm and field experiments in order to propose a new way for the valorization of miscanthus biomass. The concentration of potentially toxic elements was generally higher in stems than in leaves. Although P-fertilizers were added to contaminated soils under sustainable conditions (from 0.022% to 0.026% w/w), the average of leaf and stem biomass generally increased in the presence of P-fertilizers due to the changes in the speciation of phosphorus. Leaves of the investigated miscanthus may be of great interest as a catalyst in organic chemistry, since the Ca concentration was up to 9000 mg kg−1 DW. Stems represent a potential biomass that can be used as renewable resource of Lewis acids, currently used in organic syntheses (the sum of Zn, Cu, Mn, Fe, Mg, Si and Al was near 1000 mg kg−1 DW). The percentage of Cd and Pb in leaves and stems of miscanthus did not significantly change with P-fertilizers. Depending on the mesocosm and field experiments, it ranged from 0.004% to 0.016% and from 0.009% and 0.034% for Cd in leaves and stems, respectively, and from 0.004% to 0.015% and from 0.009% and 0.033% for Pb in leaves and stems, respectively.
Marie Hechelski; Brice Louvel; Pierrick Dufrénoy; Alina Ghinet; Christophe Waterlot. Toward a New Way for the Valorization of Miscanthus Biomass Produced on Metal-Contaminated Soils Part 1: Mesocosm and Field Experiments. Sustainability 2020, 12, 9370 .
AMA StyleMarie Hechelski, Brice Louvel, Pierrick Dufrénoy, Alina Ghinet, Christophe Waterlot. Toward a New Way for the Valorization of Miscanthus Biomass Produced on Metal-Contaminated Soils Part 1: Mesocosm and Field Experiments. Sustainability. 2020; 12 (22):9370.
Chicago/Turabian StyleMarie Hechelski; Brice Louvel; Pierrick Dufrénoy; Alina Ghinet; Christophe Waterlot. 2020. "Toward a New Way for the Valorization of Miscanthus Biomass Produced on Metal-Contaminated Soils Part 1: Mesocosm and Field Experiments." Sustainability 12, no. 22: 9370.
In the incessant search for innovative cancer control strategies, this study was devoted to the design, synthesis and pharmacological evaluation of dual inhibitors of farnesyltransferase and tubulin polymerization (FTI/MTIs). A series of indolizine-phenothiazine hybrids 16 (amides) and 17 (ketones) has been obtained in a 4-step procedure. The combination of the two heterocycles provided potent tubulin polymerization inhibitors with similar efficiency as the reference phenstatin and (-)-desoxypodophyllotoxin. Ketones 17 were also able to inhibit human farnesyltransferase (FTase) in vitro. Interestingly, three molecules 17c, 17d and 17f were very effective against both considered biological targets. Next, nine indolizine-phenothiazine hybrids 16c, 16f, 17a-f and 22b were evaluated for their cell growth inhibition potential on the NCI-60 cancer cell lines panel. Ketones 17a-f were the most active and displayed promising cellular activities. Not only they arrested the cell growth of almost all tested cancer cells, but they displayed cytotoxicity potential with GI50 values in the low nanomolar range. The most sensitive cell lines upon treatment with indolizine-phenothiazine hybrids were NCI-H522 (lung cancer), COLO-205 and HT29 (colon cancer), SF-539 (human glioblastoma), OVCAR-3 (ovarian cancer), A498 (renal cancer) and especially MDA-MB-435 (melanoma). Demonstrating the preclinical effectiveness of these dual inhibitors can be crucial. A single dual molecule could induce a synergy of antitumor activity, while increasing the effectiveness and reducing the toxicity of the classical combo treatments currently used in chemotherapy.
Iuliana-Monica Moise; Elena Bîcu; Amaury Farce; Joëlle Dubois; Alina Ghinet. Indolizine-phenothiazine hybrids as the first dual inhibitors of tubulin polymerization and farnesyltransferase with synergistic antitumor activity. Bioorganic Chemistry 2020, 103, 104184 .
AMA StyleIuliana-Monica Moise, Elena Bîcu, Amaury Farce, Joëlle Dubois, Alina Ghinet. Indolizine-phenothiazine hybrids as the first dual inhibitors of tubulin polymerization and farnesyltransferase with synergistic antitumor activity. Bioorganic Chemistry. 2020; 103 ():104184.
Chicago/Turabian StyleIuliana-Monica Moise; Elena Bîcu; Amaury Farce; Joëlle Dubois; Alina Ghinet. 2020. "Indolizine-phenothiazine hybrids as the first dual inhibitors of tubulin polymerization and farnesyltransferase with synergistic antitumor activity." Bioorganic Chemistry 103, no. : 104184.
A particular reactivity of 1-cyanomethylpyridinium salts was revealed in the [3 + 2] cycloaddition conditions with alkyl propiolates. Cycloadducts 3 were obtained in reactions carried out at room temperature while refluxing in CH3CN provided unexpected ethyl or methyl 3-(3-cyanoimidazo[1,2-a]pyridin-2-yl)indolizine-1-carboxylates 4. The structure of the new 2:1 azaindolizine-indolizine adducts was secured by X-ray analysis. Methodological efforts have enabled the adjustment of the reactivity towards the formation of 3-cyanoindolizines 3 or cyanoazaindolizine-indolizines 4. A mechanism for the formation of azaindolizine-indolizines was proposed. A portfolio of rare cyanoindolizines and cyanoazaindolizine-indolizines has been successfully obtained.
Iuliana-Monica Moise; Alina Ghinet; Sergiu Shova; Elena Bîcu. Switching the reactivity of cyanomethylpyridinium salts in the 1,3-cycloaddition conditions with alkyl propiolates to cyanoindolizines or cyanoazaindolizinyl-indolizines. Tetrahedron 2020, 76, 131502 .
AMA StyleIuliana-Monica Moise, Alina Ghinet, Sergiu Shova, Elena Bîcu. Switching the reactivity of cyanomethylpyridinium salts in the 1,3-cycloaddition conditions with alkyl propiolates to cyanoindolizines or cyanoazaindolizinyl-indolizines. Tetrahedron. 2020; 76 (41):131502.
Chicago/Turabian StyleIuliana-Monica Moise; Alina Ghinet; Sergiu Shova; Elena Bîcu. 2020. "Switching the reactivity of cyanomethylpyridinium salts in the 1,3-cycloaddition conditions with alkyl propiolates to cyanoindolizines or cyanoazaindolizinyl-indolizines." Tetrahedron 76, no. 41: 131502.
The aim of this study was to determine the impact of the origin and the manufacturing processes of the chiral stationary phases (CSPs) on their chromatographic behaviors. Hence, four chiral stationary phases based on immobilized tris (3,5-dichlorophenylcarbamate) derivative of cellulose supplied by four different manufacturers were evaluated. A set of twenty-nine compounds, including commercially available and in-house synthesized compounds, with a broad range of lipophilicity and polarity was chosen. Three main parameters were evaluated on all stationary phases: retention factor, selectivity and loading capacity. This work highlighted that the retention factor strongly varied according to the manufacturer. Regardless of the characteristic of the tested compounds i.e. neutral, acidic or basic, there was a trend in retention ability of the four chiral stationary phases: retention was increasing from CHIRAL ART Cellulose-SC, REFLECT I-Cellulose C, Chiralpak IC to Lux i-Cellulose-5. On the contrary, selectivity did not follow the same trend as retention. The difference in selectivity between each column towards one compound was quite low while the difference in resolution depended on the nature of the compounds investigated and was significant in certain cases. Finally, the four different columns presented similar and high loading capacity.
Anca-Elena Dascalu; David Speybrouck; Muriel Billamboz; David Corens; Alina Ghinet; Emmanuelle Lipka. Analytical and preparative enantioseparations in supercritical fluid chromatography using different brands of immobilized cellulose tris (3,5-dichlorophenylcarbamate) columns: Some differences. Journal of Chromatography A 2020, 1622, 461125 .
AMA StyleAnca-Elena Dascalu, David Speybrouck, Muriel Billamboz, David Corens, Alina Ghinet, Emmanuelle Lipka. Analytical and preparative enantioseparations in supercritical fluid chromatography using different brands of immobilized cellulose tris (3,5-dichlorophenylcarbamate) columns: Some differences. Journal of Chromatography A. 2020; 1622 ():461125.
Chicago/Turabian StyleAnca-Elena Dascalu; David Speybrouck; Muriel Billamboz; David Corens; Alina Ghinet; Emmanuelle Lipka. 2020. "Analytical and preparative enantioseparations in supercritical fluid chromatography using different brands of immobilized cellulose tris (3,5-dichlorophenylcarbamate) columns: Some differences." Journal of Chromatography A 1622, no. : 461125.
Twenty-eight 5-pyrrolidine-2-ones decorated by hydrazine or acyl hydrazones groups have been designed, synthesized and evaluated as antifungal agents on a panel of twelve fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. Half of the target compounds exhibited good to high antifungal activities on at least one strain with MIC50 lower than the control antifungal agent – hymexazol or ketoconazole. 5-Arylhydrazino-pyrrolidin-2-ones were found active and the –NH-NH- linker proved to be essential to maintain the antifungal potential. Compound 2a is a broad-spectrum antifungal, active on 60% of the tested strains. Replacing the hydrazine linker by an acylhydrazone one narrowed the spectrum of activity but pyroglutamylaryl hydrazones, mainly aromatic ones, exhibited good activity, adequate “fungicide-like” properties and were devoted of cytotoxicity.
Anca-Elena Dascalu; Alina Ghinet; Emmanuelle Lipka; Christophe Furman; Benoît Rigo; Antoine Fayeulle; Muriel Billamboz. Design, synthesis and evaluation of hydrazine and acyl hydrazone derivatives of 5-pyrrolidin-2-one as antifungal agents. Bioorganic & Medicinal Chemistry Letters 2020, 30, 127220 .
AMA StyleAnca-Elena Dascalu, Alina Ghinet, Emmanuelle Lipka, Christophe Furman, Benoît Rigo, Antoine Fayeulle, Muriel Billamboz. Design, synthesis and evaluation of hydrazine and acyl hydrazone derivatives of 5-pyrrolidin-2-one as antifungal agents. Bioorganic & Medicinal Chemistry Letters. 2020; 30 (13):127220.
Chicago/Turabian StyleAnca-Elena Dascalu; Alina Ghinet; Emmanuelle Lipka; Christophe Furman; Benoît Rigo; Antoine Fayeulle; Muriel Billamboz. 2020. "Design, synthesis and evaluation of hydrazine and acyl hydrazone derivatives of 5-pyrrolidin-2-one as antifungal agents." Bioorganic & Medicinal Chemistry Letters 30, no. 13: 127220.
A broad range of chalcones and derivatives were easily and rapidly synthesized, following Claisen-Schmidt condensation of (hetero)aryl ketones and (hetero)aryl aldehydes using a ultrasound probe. A comparison was made with classical magnetic stirring experiments, and an optimization study was realized, showing lithium hydroxide to be the best basic catalyst of the studied condensations. By-products of the reactions (β-hydroxy-ketone, diketones, and cyclohexanols) were also isolated. All compounds were evaluated in vitro for their ability to inhibit human farnesyltransferase, a protein implicated in cancer and rare diseases and on the NCI-60 cancer cell lines panel. Molecules showed inhibitory activity on the target protein and cytostatic effect on different cell lines with particular activity against MCF7, breast cancer cells.
Germain Homerin; Adrian Sorin Nica; Amaury Farce; Joëlle Dubois; Alina Ghinet. Ultrasounds-mediated 10-seconds synthesis of chalcones as potential farnesyltransferase inhibitors. Bioorganic & Medicinal Chemistry Letters 2020, 30, 127149 .
AMA StyleGermain Homerin, Adrian Sorin Nica, Amaury Farce, Joëlle Dubois, Alina Ghinet. Ultrasounds-mediated 10-seconds synthesis of chalcones as potential farnesyltransferase inhibitors. Bioorganic & Medicinal Chemistry Letters. 2020; 30 (11):127149.
Chicago/Turabian StyleGermain Homerin; Adrian Sorin Nica; Amaury Farce; Joëlle Dubois; Alina Ghinet. 2020. "Ultrasounds-mediated 10-seconds synthesis of chalcones as potential farnesyltransferase inhibitors." Bioorganic & Medicinal Chemistry Letters 30, no. 11: 127149.
The chromatographic properties of a new coated amylose tris(3-chloro-5-methylphenylcarbamate) were evaluated in supercritical fluid chromatography for the separation of enantiomers of chiral 1-aryl-5-aryl-pyrrolidin-2-one derivatives, potential anticancer agents, and some commercial drugs. The mobile phase consisted of CO2-modifier mixtures with 30% of either methanol or ethanol, the flow rate was 3 mL/min. The column oven temperature was 40 °C and the outlet pressure was 15 MPa, in order to limit the compressibility of the CO2, thus limiting density variation along the column. The obtained results were then compared to those observed toward 3 other stationary phases: the coated amylose tris(3,5-dimethylphenylcarbamate), the immobilized amylose tris(3,5-dimethylphenylcarbamate) and the coated amylose tris(5-chloro-2-methylphenylcarbamate). It was shown that the new coated amylose tris(3-chloro-5-methylphenylcarbamate) was the most retentive column whatever the studied compounds, particularly for thalidomide and omeprazole with retention factors up to 73.3 and 29.5for the second enantiomer, respectively. Concerning the enantioselectivity, even most of the compounds are separated on all the four columns, the coated amylose tris(3-chloro-5-methylphenylcarbamate) allows the best resolution for most of the ten studied analytes (except omeprazole for which the resolution values are equal to 7.8 and 9.7 on the coated amylose tris(3-chloro-5-methylphenylcarbamate) and amylose tris(3,5-dimethylphenylcarbamate), respectively). Acting in complementary ways, the two chlorinated stationary phases permitted the complete separation of enantiomers of nine compounds out of the ten.
Anca-Elena Dascalu; Alina Ghinet; Bezhan Chankvetadze; Emmanuelle Lipka. Comparison of dimethylated and methylchlorinated amylose stationary phases, coated and covalently immobilized on silica, for the separation of some chiral compounds in supercritical fluid chromatography. Journal of Chromatography A 2020, 1621, 461053 .
AMA StyleAnca-Elena Dascalu, Alina Ghinet, Bezhan Chankvetadze, Emmanuelle Lipka. Comparison of dimethylated and methylchlorinated amylose stationary phases, coated and covalently immobilized on silica, for the separation of some chiral compounds in supercritical fluid chromatography. Journal of Chromatography A. 2020; 1621 ():461053.
Chicago/Turabian StyleAnca-Elena Dascalu; Alina Ghinet; Bezhan Chankvetadze; Emmanuelle Lipka. 2020. "Comparison of dimethylated and methylchlorinated amylose stationary phases, coated and covalently immobilized on silica, for the separation of some chiral compounds in supercritical fluid chromatography." Journal of Chromatography A 1621, no. : 461053.
The majority of cancers detected every year are treated with anti-cancer compounds. Unfortunately, many tumors become resistant to antineoplastic drugs. One option is to use cocktails of compounds acting on different targets to try to overcome the resistant cells. This type of approach can produce good results, but is often accompanied by a sharp increase of associated side effects. The strategy presented herein focuses on the use of a single compound acting on two different biological targets enhancing potency and lowering the toxicity of the chemotherapy. In this light, the approach presented in the current study involves the dual inhibition of human pyruvate dehydrogenase kinase-1 (PDHK1) and tubulin polymerization using mono-, di- and tri-chloroacetate-loaded benzophenones and benzothiophenones. Synthesized molecules were evaluated in vitro on tubulin polymerization and on pyruvate dehydrogenase kinase 1. The cell cycle distribution after treatment of DA1-3b leukemic cells with active compounds was tested. Twenty-two benzo(thio)phenones have been selected by the National Cancer Institute (USA) for evaluation of their anti-proliferative potential against NCI-60 cancer cell lines including multidrug-resistant tumor cell lines. Seventeen molecules proved to be very effective in combating the growth of tumor cells exhibiting inhibitory activities up to nanomolar range. The molecular docking of best antitumor molecules in the study was realized with GOLD in the tubulin and PDHK1 binding sites, and allowed to understand the positioning of active molecules. Chloroacetate-loaded benzo(thio)phenones are dual targeted tubulin- and pyruvate dehydrogenase kinase 1 (PDHK1)-binding antitumor agents and exhibited superior antitumor activity compared to non-chlorinated congeners particularly on leukemia, colon, melanoma and breast cancer cell lines.
Alina Ghinet; Xavier Thuru; Emilie Floquet; Joëlle Dubois; Amaury Farce; Benoît Rigo. Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands. Bioorganic Chemistry 2020, 96, 103643 .
AMA StyleAlina Ghinet, Xavier Thuru, Emilie Floquet, Joëlle Dubois, Amaury Farce, Benoît Rigo. Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands. Bioorganic Chemistry. 2020; 96 ():103643.
Chicago/Turabian StyleAlina Ghinet; Xavier Thuru; Emilie Floquet; Joëlle Dubois; Amaury Farce; Benoît Rigo. 2020. "Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands." Bioorganic Chemistry 96, no. : 103643.
New environment friendly approach for the synthesis of idrocilamide (1), the marketed myorelaxant and anti-inflammatory agent, is reported. The synthetic strategy involves a solvent free aminolysis reaction catalyzed by different zinc-containing catalysts: ZnCl2, montmorillonite K10 impregnated with ZnCl2 or ecocatalysts. The latter have been prepared from the aerial parts of Lolium perenne L. plants grown on contaminated soils from North of France region The best aminolysis catalysts in the current study (ZnCl2 and Ecocat2) have been selected for additional aminolyses. Ecocat2 had the advantage of being reusable over five runs and constituted a sustainable catalyst allowing a green route to idrocilamide. Ecocat2 proved to be a versatile catalyst for amide bond formation via aminolysis of different methyl esters. Synthesized derivatives 1-4, 6 and 9 have been first evaluated for their effect on reactive oxygen species (ROS) generation from macrophages and displayed antioxidant properties by preventing ROS generation. Next, the analysis of the effect of molecules 1-4, 6 and 9 on macrophage migration between epithelial cells to human opportunistic fungus Candida albicans indicated that molecules 2-4, 6 and 9 exert anti-inflammatory properties via reducing macrophage migration while parent idrocilamide (1) did not show any significant effect. This work opens the way for the discovery of new analogues of idrocilamide with improved antioxidant and anti-inflammatory properties.
Pierrick Dufrénoy; Rogatien Charlet; Marie Hechelski; Adam Daïch; Christophe Waterlot; Samir Jawhara; Alina Ghinet. New Efficient Eco‐Friendly Supported Catalysts for the Synthesis of Amides with Antioxidant and Anti‐Inflammatory Properties. ChemMedChem 2020, 15, 459 -467.
AMA StylePierrick Dufrénoy, Rogatien Charlet, Marie Hechelski, Adam Daïch, Christophe Waterlot, Samir Jawhara, Alina Ghinet. New Efficient Eco‐Friendly Supported Catalysts for the Synthesis of Amides with Antioxidant and Anti‐Inflammatory Properties. ChemMedChem. 2020; 15 (5):459-467.
Chicago/Turabian StylePierrick Dufrénoy; Rogatien Charlet; Marie Hechelski; Adam Daïch; Christophe Waterlot; Samir Jawhara; Alina Ghinet. 2020. "New Efficient Eco‐Friendly Supported Catalysts for the Synthesis of Amides with Antioxidant and Anti‐Inflammatory Properties." ChemMedChem 15, no. 5: 459-467.
Imidazo[1,2‐a]pyridines (azaindolizines) 1a‐k have been designed and easily synthesized by the [3+2] cycloaddition reaction between cycloimmonium salts and ethyl cyanoformate used as dipolarophile. The behavior of the latter in cycloaddition reactions has been studied using different pyridinium, (iso)quinolinium or benzimidazolium salts and demonstrated the substrate‐dependent reactivity, and the observation in many cases of its reaction as a cyano or an ethoxycarbonyl donor reagent. New chemical platforms have been identified thanks to the different reactivity of ethyl cyanoformate. Final molecules were subjected to a biological evaluation on ESKAPE pathogens (five bacteria: Escherichia coli, Klebsiella pneumoniae (MDR), Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus (MRSA) and two fungi: Cryptococcus neoformans (H99) and Candida albicans). Azaindolizines 1b and 1e displayed antifungal activity on Candida albicans and ylide 11 inhibited both fungi Candida albicans and Cryptococcus neoformans. These results open the way for the development of analogues with improved antifungal activity.
Anca‐Elena Dascălu; Elena Bîcu; Segiu Shova; Emmanuelle Lipka; Benoît Rigo; Muriel Billamboz; Alina Ghinet. Insights on the Chemical Behavior of Ethyl Cyanoformate: Dipolarophile, Cyano or Ethoxycarbonyl Source. ChemistrySelect 2019, 4, 13724 -13730.
AMA StyleAnca‐Elena Dascălu, Elena Bîcu, Segiu Shova, Emmanuelle Lipka, Benoît Rigo, Muriel Billamboz, Alina Ghinet. Insights on the Chemical Behavior of Ethyl Cyanoformate: Dipolarophile, Cyano or Ethoxycarbonyl Source. ChemistrySelect. 2019; 4 (46):13724-13730.
Chicago/Turabian StyleAnca‐Elena Dascălu; Elena Bîcu; Segiu Shova; Emmanuelle Lipka; Benoît Rigo; Muriel Billamboz; Alina Ghinet. 2019. "Insights on the Chemical Behavior of Ethyl Cyanoformate: Dipolarophile, Cyano or Ethoxycarbonyl Source." ChemistrySelect 4, no. 46: 13724-13730.
A restoration of highly contaminated garden soil is proposed as a greener alternative to the production of vegetables. Depending on potentially toxic elements and their concentration, ryegrass shoots accumulate these elements in sufficient quantity to be used as a catalyst in organic synthesis. The analysis of Cd, Pb, Zn, Cu, Fe, Mn, and Al in ashes issued from the calcination of ryegrass shoots revealed that the concentration of Zn was highest (>7000 mg kg–1). The ratios between potential Lewis acids (Zn, Cu, Fe, Mn, and Al) to carcinogenic metals (Cd or Pb) were 191 ± 7 for LA/Cd and 235 ± 13 for LA/Pb, making the shoots of ryegrass suitable for the production of Zn-rich polymetallic biosourced catalysts. This material was used in the synthesis of idrocilamide under free-solvent condition, providing the drug in a good yield (69.9%). Data show that a limitation of waste, a maximization of the material incorporation in the process, a minimization of the steps, and an optimization of the stoichiometric factor are the main innovative factors in the current process in comparison with those previously reported.
Christophe Waterlot; Pierrick Dufrénoy; Marie Hechelski; Brice Louvel; Adam Daïch; Alina Ghinet. Benefits of Ryegrass on Multicontaminated Soils Part 2: A Green Process to Provide Idrocilamide. Sustainability 2019, 11, 6685 .
AMA StyleChristophe Waterlot, Pierrick Dufrénoy, Marie Hechelski, Brice Louvel, Adam Daïch, Alina Ghinet. Benefits of Ryegrass on Multicontaminated Soils Part 2: A Green Process to Provide Idrocilamide. Sustainability. 2019; 11 (23):6685.
Chicago/Turabian StyleChristophe Waterlot; Pierrick Dufrénoy; Marie Hechelski; Brice Louvel; Adam Daïch; Alina Ghinet. 2019. "Benefits of Ryegrass on Multicontaminated Soils Part 2: A Green Process to Provide Idrocilamide." Sustainability 11, no. 23: 6685.
This report deals with the design, the synthesis and the pharmacological evaluation of pyroglutamide-based P2X7 antagonists. A dozen were shown to possess improved properties, among which inhibition of YO-PRO-1/TO-PRO-3 uptake and IL1β release upon BzATP activation of the receptor and dampening signs of DSS-induced colitis on mice, in comparison with reference antagonist GSK1370319A. Docking study and biological evaluation of synthesized compounds has highlighted new SAR, and low toxicity profiles of pyroglutamides herein described are clues for the finding of a usable h-P2X7 antagonist drug. Such a drug would raise the hope for a cure to many P2X7-dependant pathologies, including inflammatory, neurological and immune diseases.
Germain Homerin; Samir Jawhara; Xavier Dezitter; Davy Baudelet; Pierrick Dufrénoy; Benoît Rigo; Régis Millet; Christophe Furman; Guillaume Ragé; Emmanuelle Lipka; Amaury Farce; Nicolas Renault; Boualem Sendid; Rogatien Charlet; Jordan Leroy; Mélodie Phanithavong; Camille Richeval; Jean-François Wiart; Delphine Allorge; Sahil Adriouch; Valérie Vouret-Craviari; Alina Ghinet. Pyroglutamide-Based P2X7 Receptor Antagonists Targeting Inflammatory Bowel Disease. Journal of Medicinal Chemistry 2019, 63, 2074 -2094.
AMA StyleGermain Homerin, Samir Jawhara, Xavier Dezitter, Davy Baudelet, Pierrick Dufrénoy, Benoît Rigo, Régis Millet, Christophe Furman, Guillaume Ragé, Emmanuelle Lipka, Amaury Farce, Nicolas Renault, Boualem Sendid, Rogatien Charlet, Jordan Leroy, Mélodie Phanithavong, Camille Richeval, Jean-François Wiart, Delphine Allorge, Sahil Adriouch, Valérie Vouret-Craviari, Alina Ghinet. Pyroglutamide-Based P2X7 Receptor Antagonists Targeting Inflammatory Bowel Disease. Journal of Medicinal Chemistry. 2019; 63 (5):2074-2094.
Chicago/Turabian StyleGermain Homerin; Samir Jawhara; Xavier Dezitter; Davy Baudelet; Pierrick Dufrénoy; Benoît Rigo; Régis Millet; Christophe Furman; Guillaume Ragé; Emmanuelle Lipka; Amaury Farce; Nicolas Renault; Boualem Sendid; Rogatien Charlet; Jordan Leroy; Mélodie Phanithavong; Camille Richeval; Jean-François Wiart; Delphine Allorge; Sahil Adriouch; Valérie Vouret-Craviari; Alina Ghinet. 2019. "Pyroglutamide-Based P2X7 Receptor Antagonists Targeting Inflammatory Bowel Disease." Journal of Medicinal Chemistry 63, no. 5: 2074-2094.