Project description:Heteroaromatic analogs of DMU-212 (8-15) have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. These novel analogs contain a trans-3,4,5-trimethoxystyryl moiety attached to the C2 position of indole, benzofuran, benzothiazole or benzothiophene ring (8, 11, 13 and 14, respectively) and showed potent growth inhibition in 85% of the cancer cell lines examined, with GI50 values <1 μM. Interestingly, trans-3,4- and trans-3,5-dimethoxystyryl DMU-212 analogs 9, 10, 12 and 15 exhibited significantly less growth inhibition than their 3,4,5-trimethoxystyryl counterparts, suggesting that the trans-3,4,5-trimethoxystyryl moiety is an essential structural element for the potent anti-cancer activity of these heterocyclic DMU-212 analogs. Molecular modeling studies showed that the four most active compounds (8, 11, 13 and 14) all bind to the colchicine binding site on tubulin, and that their binding modes are similar to that of DMU-212.
Project description:This study investigated the physico-chemical and textural properties of 3D-printed pea protein-only and pea protein-chicken-based hybrid meat analogs. Both pea protein isolate (PPI)-only and hybrid cooked meat analogs had a similar moisture content of approximately 70%, which was similar to that of chicken mince. However, the protein content increased significantly with the amount of chicken in the hybrid paste undergoing 3D printing and cooking. Significant differences were observed in the hardness values of the non-printed cooked pastes and the 3D printed cooked counterparts, suggesting that the 3D printing process reduces the hardness of the samples and is a suitable method to produce a soft meal, and has significant potential in elderly health care. Scanning electron microscopy (SEM) revealed that adding chicken to the plant protein matrix led to better fiber formation. PPI itself was not able to form any fibers merely by 3D printing and cooking in boiling water. Protein-protein interactions were also studied through the protein solubility test, which indicated that hydrogen bonding was the major bonding that contributed to the structure formation in cooked printed meat analogs. In addition, disulfide bonding was correlated with improved fibrous structures, as observed through SEM.
Project description:trans-Resveratrol (RSV) is a natural phenolic molecule of the stilbene family known for its anti-oxidant properties in the field of nutraceuticals and cosmetics. Its production by grapevine cell suspensions is induced by the addition to the culture medium of elicitor compounds, methyl jasmonate (MeJA) and cyclodextrins (CDs). Physico-chemical studies were performed to understand the mechanism of action of CDs on this bioproduction of RSV. Inclusion complexes of RSV in CDs were first observed and then interactions with MeJA were identified using various analytical techniques such as UV and nuclear magnetic resonance (NMR) spectroscopies, mass spectrometry (MS) and isothermal titration calorimetry (ITC).
Project description:The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.
Project description:The transthyretin amyloidoses are a subset of protein misfolding diseases characterized by the extracellular deposition of aggregates derived from the plasma homotetrameric protein transthyretin (TTR) in peripheral nerves and the heart. We have established a robust disease-relevant human cardiac tissue culture system to explore the cytotoxic effects of amyloidogenic TTR variants. We have employed this cardiac amyloidosis tissue culture model to screen 23 resveratrol analogs as inhibitors of amyloidogenic TTR-induced cytotoxicity and to investigate their mechanisms of protection. Resveratrol and its analogs kinetically stabilize the native tetramer preventing the formation of cytotoxic species. In addition, we demonstrate that resveratrol can accelerate the formation of soluble non-toxic aggregates and that the resveratrol analogs tested can bring together monomeric TTR subunits to form non-toxic native tetrameric TTR.
Project description:Developing greener hydrometallurgical processes implies offering alternatives to conventional solvents used for liquid-liquid extraction (LLE) of metals. In this context, it is proposed to substitute the organic phase by a hydrophobic silica-based porous liquid (PL). Two different sulfonated hollow silica particles (HSPs) are modified with various polyethoxylated fatty amines (EthAs) forming a canopy that provides both the targeted hydrophobicity and liquefying properties. This study shows that these properties can be tuned by varying the number of ethylene oxide units in the EthA: middle-range molecular weight EthAs allow obtaining a liquid at room temperature, while too short or too long EthA leads to solid particles. Viscosity is also impacted by the density and size of the silica spheres: less viscous PLs are obtained with small low-density spheres, while for larger spheres (c.a. 200 nm) the density has a less significant impact on viscosity. According to this approach, hydrophobic PLs are successfully synthesized. When contacted with an aqueous phase, the most hydrophobic PLs obtained allow a subsequent phase separation. Preliminary extraction tests on three rare earth elements have further shown that functionalization of the PL is necessary to observe metal extraction.
Project description:A group of four selected non-ionic surfactants based on carbohydrates, namely octyl d-xyloside (C8X), nonyl d-xyloside (C9X), decyl d-xyloside (C10X) and dodecyl d-xyloside (C12X), have been investigated to accomplish a better understanding of their physico-chemical properties as well as biological activities. The surface-active properties, such as critical micelle concentration (CMC), emulsion and foam stability, the impact of the compounds on cell surface hydrophobicity and cell membrane permeability together with their toxicity on the selected bacterial strains have been determined as well. The studied group of surfactants showed high surface-active properties allowing a decrease in the surface tension to values below 25 mN m-1 for dodecyl d-xyloside at the CMC. The investigated compounds did not have any toxic influence on two Pseudomonas bacterial strains at concentrations below 25 mg L-1. The studied long-chain alkyl xylosides influenced both the cell inner membrane permeability and the cell surface hydrophobicity. Furthermore, the alkyl chain length, as well as the surfactant concentration, had a significant impact on the modifications of the cell surface properties. The tested non-ionic surfactants exhibited strong surface-active properties accompanied by the significant influence on growth and properties of Pseudomonas bacteria cells.
Project description:A series of imidazolium-based symmetrical and asymmetrical dicationic ionic liquids (DcILs) with alkyl spacers of different length and with [FeCl3 Br]- as counter ion have been synthesized. The synthesized DcILs are characterized by using FTIR and Raman spectroscopy as well as mass spectrometry, along with single-crystal XRD analysis. Physicochemical properties such as solubility, thermal stability and magnetic susceptibility are also measured. These compounds show low melting points, good solubility in water and organic solvents, thermal stability, and paramagnetism. The products of molar susceptibility and temperature (χmol ⋅T) for the synthesized DcILs have been found between 4.05 to 4.79 emu mol-1 K Oe-1 and effective magnetic moment values have also been determined to be compared to that expected from the spin-only approximation.
Project description:A series of dicationic ionic liquids (ILs) including [C4(MIM)2][PF6]2, [C5(MIM)2][PF6]2, [C6(MIM)2][PF6]2 and [C4(PYR)2][PF6]2 were synthesized. Their thermal stability and melting points were analysed. It was found that dicationic ILs presented important implications in the design of homogeneous and heterogeneous system with water. A homogeneous system of dicationic ILs with water could be formed at a relatively high temperature and then a heterogeneous system was formed when the solution was cooled to a low temperature. The ILs recovered by altering the temperature were obtained in high percentage yields of [C4(MIM)2][PF6]2 (97.6%), [C5(MIM)2][PF6]2 (97.3%), [C6(MIM)2][PF6]2 (98.0%) and [C4(PYR)2][PF6]2 (94.2%). On the other hand, [C4(MIM)2][PF6]2 and [C5(MIM)2][PF6]2 exhibited good solubility in acetonitrile and acetone. A homogeneous system could be achieved with imidazolium-based ILs with a relatively low amount of water and acetonitrile at room temperature. All of the properties of dicationic ILs have a strong correlation with the nature of dications, the linkage chain and the symmetry of dications. Dicationic ILs may provide a new opportunity for some specific applications in order to enable the effective separation and isolation of products.
Project description:In this paper, the results on the fabrication of ferroelectric membranes as vascular patches with modified surfaces are presented. For the modification of a membrane surface contacting blood, DLC coating was deposited using the pulsed vacuum arc deposition technique. The physico-chemical properties and cytotoxicity of the membranes modified under various conditions were studied. It was found that DLC coatings do not affect membrane microstructure, preserving its crystal structure as well as its high strength and elongation. It was revealed that an increase in the capacitor storage voltage results in the rise in sp2- and sp-hybridized carbon concentration, which makes it possible to control the chemical structure and surface energy of the modified surface. The experiments with 3T3L1 fibroblasts showed no toxic effects of the materials extracts.