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91.
Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites
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Dr. Marie‐Aude Richard Dr. Didier Hamels Dr. Pascal Pigeon Dr. Siden Top Dr. Patrick M. Dansette Hui Zhi Shirley Lee Dr. Anne Vessières Dr. Daniel Mansuy Prof. Gérard Jaouen 《ChemMedChem》2015,10(6):981-990
Ferrociphenols have been found to have high antiproliferative activity against estrogen‐independent breast cancer cells. The rat and human liver microsome‐mediated metabolism of three compounds of the ferrocifen ( FC ) family, 1,1‐bis(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC1 ), 1‐(4‐hydroxyphenyl)‐1‐(phenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC2 ), and 1‐[4‐(3‐dimethylaminopropoxy)phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC3 ), was studied. Three main metabolite classes were identified: quinone methides ( QM s) deriving from two‐electron oxidation of FC s, cyclic indene products ( CP s) deriving from acid‐catalyzed cyclization of QM s, and allylic alcohols ( AA s) deriving from hydroxylation of FC s. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N‐benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450‐dependent oxidation of the phenol function and hydroxylation of the allylic CH2 group of FC s leads to the formation of QM and AA metabolites, respectively. Some of the new ferrociphenols obtained in this study were found to exhibit remarkable antiproliferative effects toward MDA‐MB‐231 hormone‐independent breast cancer cells. 相似文献
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In-situ fabrication of polyacrylate-silver nanocomposite through photoinduced tandem reactions involving eosin dye 总被引:1,自引:0,他引:1
A silver-acrylate nanocomposite was prepared using a novel one-pot strategy involving eosin dye as visible sensitizer and an amine derivative as radicals' source. The mechanism highlighted by steady state photolysis and time-resolved absorption spectroscopy lies on the initial formation of a strong ion-pair complex between eosin and Ag+. Upon visible irradiation, the excited triplet state of the metal complex efficiently abstracts a hydrogen atom from the amine and produces an α-aminoalkyl radical. In acrylate monomer matrix, such a strong reactive species initiates a free radical photopolymerization and also provides the reduction of the silver cation. Through this ‘in-situ’ fabrication method, the kinetics formation of the nanocomposite and its detailed structural analysis are characterized by UV-visible, real-time FTIR absorption spectroscopy and by transmission electron microscopy. 相似文献
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The development of a conducting composite from its one-step synthesis in aqueous dispersed medium to the characterization of its chemical sensor performance is detailed. Composite films of polyaniline and polyacrylate were processed from the crude dispersion with no need for post-formulation. The synthesis has been optimized to be as simple, cheap and transferable as possible. The composite composition is tunable, i.e. the nature of the dopant was varied and its effect on kinetic parameters was observed. Ab initio calculations have been performed on a series of six ionic systems to gain a deeper insight into the contribution of both the stability of the anilinium salts in the composite polymerization. The conductivities of all composites were recorded from room temperature to 150 °C and the thermal stability versus dopant highlighted. The conducting films were then studied as active layers in a chemical sensor. The results showed that these composites, easily synthesized and processed, are ammonia sensitive and exhibit a fast response when exposed to air pollution. 相似文献
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Geoffray Labar Cédric Bauvois Dr. Franck Borel Dr. Jean‐Luc Ferrer Dr. Johan Wouters Prof. Didier M. Lambert Prof. 《Chembiochem : a European journal of chemical biology》2010,11(2):218-227
2‐Arachidonoylglycerol plays a major role in endocannabinoid signaling, and is tightly regulated by the monoacylglycerol lipase (MAGL). Here we report the crystal structure of human MAGL. The protein crystallizes as a dimer, and despite structural homologies to haloperoxidases and esterases, it distinguishes itself by a wide and hydrophobic access to the catalytic site. An apolar helix covering the active site also gives structural insight into the amphitropic character of MAGL, and likely explains how MAGL interacts with membranes to recruit its substrate. Docking of 2‐arachidonoylglycerol highlights a hydrophobic and a hydrophilic cavity that accommodate the lipid into the catalytic site. Moreover, we identified Cys201 as the crucial residue in MAGL inhibition by N‐arachidonylmaleimide, a sulfhydryl‐reactive compound. Beside the advance in the knowledge of endocannabinoids degradation routes, the structure of MAGL paves the way for future medicinal chemistry works aimed at the design of new drugs exploiting 2‐arachidonoylglycerol transmission. 相似文献
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Illa Tea Thierry Genter Norbert Naulet Marie Lummerzheim Didier Kleiber 《Journal of the science of food and agriculture》2007,87(15):2853-2859
BACKGROUND: Optimization of nitrogen (N) and sulfur (S) nutrition of wheat influences the bread‐making quality of grain. This study was conducted to determine whether the application of N and S in winter wheat at anthesis stage during two field trials could influence the absorption and distribution of N and S in grain and flour bread‐making quality RESULTS: The incorporation of 15N and 34S tracers in various plant parts (leaves, stems, spikes) was determined by isotopic ratio mass spectrometry coupled with an elemental analyser (EA‐IRMS). The effects of foliar fertilization on percentage of 15N and 34S recovery in various plant parts, grain yield, flour protein content, and dough properties were investigated after a combination of treatments: N (urea), S (micronized elemental S) and NS (both urea and micronized elemental S). Nitrogen (70–80%) and S (35–55%) were quickly assimilated during the days following application. Sixty days after application, 42–68% N and 6–12% S were recovered in the grain. When N and S fertilizers were applied simultaneously, N and S recoveries (68% and 12%), N/S ratios (11–14), flour protein content (115 g kg?1) and dough strength (310 × 10?4 J), swelling (21.8 mmH2O) and extensibility (96.4 mm) were increased. CONCLUSION: A synergistic effect between the foliar applied N and S fertilizers appears to increase N and S assimilation in grain and may improve bread‐making qualities. Copyright © 2007 Society of Chemical Industry 相似文献
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