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Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells
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Dr. Ramesh Dasari Annelise De Carvalho Derek C. Medellin Kelsey N. Middleton Dr. Frédéric Hague Marie N. M. Volmar Prof. Liliya V. Frolova Dr. Mateus F. Rossato Jorge J. De La Chapa Nicholas F. Dybdal‐Hargreaves Akshita Pillai Prof. Véronique Mathieu Prof. Snezna Rogelj Prof. Cara B. Gonzales Prof. João B. Calixto Prof. Antonio Evidente Dr. Mathieu Gautier Dr. Gnanasekar Munirathinam Prof. Rainer Glass Prof. Patricia Burth Dr. Stephen C. Pelly Prof. Willem A. L. van Otterlo Prof. Robert Kiss Prof. Alexander Kornienko 《ChemMedChem》2015,10(12):2014-2026
Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1‐agonist and anticancer activities. These experiments led to the identification of 9‐epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9‐Epipolygodial was found to maintain potency against apoptosis‐resistant cancer cells as well as those displaying the multidrug‐resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal–Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products. 相似文献
75.
Stéphane Mathieu Lionel Aranda Léo Portebois Sandrine Mathieu Michel Vilasi 《Oxidation of Metals》2018,90(1-2):43-63
The short-term oxidation behaviour of RA 602CA, Inconel 693, Manaurite 40XO and Sumitomo 696, which are four alloys recommended for hydrocarbon processing, was studied both in air and in Ar–H2O to determine the conditions of pre-oxidation treatments. Regardless of the considered material, the oxidation rate at 950 °C was systematically higher in Ar–H2O than in dry air. Surface examination of the Al-containing alloys indicated that they were not uniformly oxidized all over the surface. All Al-containing alloys (from 1.6 to 3.2% wt) formed an external protective alumina scale and behaved as alumina-forming alloys in dry air at 950 °C. In contrast, these alloys developed a rate-controlling chromia scale and severe internal oxidation in a H2O-containing atmosphere. Compared with their oxidation behaviour in air + H2O, the phenomenon was significantly enhanced in the atmosphere that coupled water vapour with a low oxygen pressure. Consequently, the Al-containing alloys should not be pre-oxidized in a water vapour atmosphere prior to long exposure to a corrosive atmosphere. In contrast, the chromia-forming Al-free 696 alloy exhibited identical oxidation behaviour in both atmospheres, demonstrating that the degradation of this alloy was not significantly affected by water vapour. 相似文献
76.
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
77.
Mathieu Martinez Laure Cointeaux Jean-Claude Leprêtre Patrick Judeinstein 《Journal of power sources》2010,195(18):5829-1379
The paper deals with the synthesis and characterisation of proton-conducting ionic liquids (PCILs) and their polymer electrolytes obtained by blending modified Nafion membranes with different concentrations of PCILs. The PCILs are obtained by the neutralization of triethylamine with different organic acids. The first part of the paper studies the influence of acidity and acid structure on PCIL thermal and electrochemical performance, while the second part examines membrane conductivity and reveals it to depend more on PCIL structure than on its intrinsic conductivity. At 130 °C, conductivities exceeding 10 mS cm−1 were obtained in fully anhydrous conditions. 相似文献
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Diana P. English Alessandro D. Santin 《International journal of molecular sciences》2013,14(5):10412-10437
Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE), a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents. 相似文献
80.
Prashant Sonar Luke Oldridge Andrew C. Grimsdale Klaus Müllen Mathieu Surin Roberto Lazzaroni Philippe Leclère Jason Pinto Lay-Lay Chua Henning Sirringhaus Richard H. Friend 《Synthetic Metals》2010,160(5-6):468-474
The synthesis of alternating copolymers of tetraalkylindenofluorene with bithiophene and terthiophene using Suzuki polycondensation route is reported. We report on the optical and electrochemical properties of these copolymers. AFM analysis of the microscopic morphology of thin deposits showed that the copolymer with terthiophene units produced the more ordered films, with well-defined fibrillar structures, resulting from highly-regular dense packing due to strong π–π interchain interactions, in contrast to the amorphous bithiophene copolymer. Upon testing these materials in FETs the terthienyl copolymers displayed the higher charge mobilities among the studied compounds, with values of over 10?4 cm2 V?1 s?1 being obtained. 相似文献