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Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献
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In this study, further analysis of the osmotic drying process was conducted to identify the optimum combination of parameters for drying rectangular alumina-gelatin beams. This study was designed to determine the effect of three variables related to the osmotic drying process (osmotic pressure, molecular weight, and immersion time) on the interaction between the liquid desiccant and the submerged alumina-gelatin samples. The water loss from the alumina-gelatin samples was positively correlated with the molecular weight, osmotic pressure, and immersion time. Up to 40% by weight of the initial water content was removed during the osmotic drying process. The samples also experienced solids gain due to the counterflow of solute from the liquid desiccant. The least amount of solids gain resulted from drying for the shortest immersion time at low osmotic pressure and high molecular weight. Evidence of possible interactions between variables was noted for the sintered density metric. Statistical methods were used to form regression equations for the measured responses (water loss, solids gain, bulk density). A verification experiment was conducted to compare the experimental outcomes to the predicted outcomes. The responses were simultaneously optimized to identify the combination of variable settings required to meet specified goals. In order to maximize water loss, minimize solids gain, and maximize bulk density, the ceramic-gelatin object should be immersed for approximately 60?min in an aqueous solution of 100,000?g/mol poly(ethylene oxide) at an osmotic pressure of 2.50?MPa. These values are valid for the range of parameter settings tested and the sample fabrication and drying methods used. 相似文献
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O.N. Kondrateva G.E. Nikiforova A.V. Tyurin M.A. Ryumin V.M. Gurevich A.P. Kritskaya K.S. Gavrichev 《Ceramics International》2018,44(15):18103-18107
The heat capacity of ytterbium orthovanadate was first measured by adiabatic calorimetry in the temperature range T?=?12.28–344.06?K. No obvious anomalies were observed on the curve obtained. The values of standard thermodynamic functions in the temperature range T?=?0–400 K were calculated. Based on low-temperature calorimetry data obtained, previously published data on the high-temperature heat capacity of ytterbium orthovanadate were corrected. The anomalous contribution to heat capacity for YbVO4 was compared with the data known for YbPO4. 相似文献
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S.K. Vimala Bharathi M. Maria Leena J.A. Moses C. Anandharamakrishnan 《International Journal of Food Science & Technology》2020,55(3):1238-1245
The usage of cling wraps is emerging as an easy and cost-effective approach to protect fresh-cut fruits and vegetables from dust, whilst improving visual appeal on retail counters. This study focused on developing an alternate, protein-based packaging material as a food grade cling wrap for food packaging applications. Zein-based cling wraps were produced, and their physical and mechanical characteristics were evaluated and compared with conventionally used chitosan biopolymer films and commercial synthetic polymer films. Antioxidant potential of the prepared films was studied, and the effectiveness of the developed films as anti-browning cling wraps was evaluated using studies conducted on fresh-cut apple slices at ambient conditions. Anti-browning effects were in par with polymeric counterparts; however, zein cling wraps could better prevent weight loss in apple slices. Zein-based films can be adopted as biodegradable food grade cling wraps as an alternative to chitosan and synthetic polymeric materials. 相似文献
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