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971.
972.
Dr. Florian C. Schrader Dr. Serghei Glinca Dr. Julia M. Sattler Dr. Hans‐Martin Dahse Gustavo A. Afanador Prof. Dr. Sean T. Prigge Prof. Dr. Michael Lanzer Dr. Ann‐Kristin Mueller Prof. Dr. Gerhard Klebe Prof. Dr. Martin Schlitzer 《ChemMedChem》2013,8(3):442-461
Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood‐ and pre‐erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver‐stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood‐stage parasite growth with IC50 values of 1.7 and 3.0 μM and lead to a more prominent developmental attenuation of liver‐stage parasites than the gold‐standard drug, primaquine. 相似文献
973.
Dr. Peter I. Dosa Dr. Tim Ward Dr. Rui E. Castro Prof. Dr. Cecília M. P. Rodrigues Prof. Dr. Clifford J. Steer 《ChemMedChem》2013,8(6):1002-1011
Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti‐apoptotic activity in both in vitro and in vivo models. However, its utility is hampered by limited aqueous solubility. As such, water‐soluble prodrugs of UDCA could have an advantage over the parent bile acid in indications where intravenous administration might be preferable, such as decreasing damage from stroke or acute kidney injury. Five phosphate prodrugs were synthesized, including one incorporating a novel phosphoryloxymethyl carboxylate (POMC) moiety. These prodrugs were highly water‐soluble, but showed significant differences in chemical stability, with oxymethylphosphate prodrugs being the most unstable. In a series of NMR experiments, the POMC prodrug was bioactivated to UDCA by alkaline phosphatase (AP) faster than a prodrug containing a phosphate directly attached to the alcohol at the 3‐position of UDCA. Both of these prodrugs showed significant anti‐apoptotic activity in a series of in vitro assays, although the POMC prodrug required the addition of AP for activity, while the other compound was active without exogenous AP. 相似文献
974.
Bacterial infections are a constant and serious threat to human health. With the increase of multidrug resistance of clinically pathogenic bacteria, common antibiotic therapies have been less effective. Fatty acid synthesis type II (FASII) system enzymes are essential for bacterial membrane lipid biosynthesis and represent increasingly promising targets for the discovery of antibacterial agents with new mechanisms of action. This review highlights recent advances in inhibitors of bacterial FASII as potential antibacterial agents, paying special attention to the activities, mechanisms, and structure–activity relationships of those inhibitors that mainly target β‐ketoacyl‐ACP synthase, β‐ketoacyl‐ACP reductase, β‐hydroxyacyl‐ACP dehydratase, and enoyl‐ACP reductase. Although inhibitors with low nanomolar and selective activity against various bacterial FASII have entered clinical trials, further research is needed to expand upon both available and yet unknown scaffolds to identify new FASII inhibitors that may have antibacterial potential, particularly against resistant bacterial strains. 相似文献
975.
Álvaro Fernández‐Cuesta José M. Fernández‐Martínez Rafel Socias i Company Leonardo Velasco 《European Journal of Lipid Science and Technology》2013,115(2):211-216
Almond kernels show large variability for oil content and fatty acid profile. The objective of this research was to evaluate the potential of near infrared (NIR) reflectance spectroscopy (NIRS) for the analysis of these traits in almond flour. Ground kernels of 181 accessions collected in 2009 were used for developing calibration equations for oil content and concentrations of individual fatty acids. Calibration equations were developed using second derivative transformation and modified partial least squares regression. They were validated with samples from 179 accessions collected in 2010. The accuracy of calibration equations was measured through the coefficient of determination (r2) in external validation and the ratio of the SD in the validation set to the standard error of prediction (RPD). Both r2 and RPD were high for oil content (r2 = 0.99; RPD = 9.24) and concentrations of oleic (r2 = 0.97; RPD = 5.37) and linoleic acids (r2 = 0.98; RPD = 7.35), revealing that calibration equations for these traits are highly accurate. Conversely, the accuracy of the calibration equations for palmitic (r2 = 0.54; RPD = 1.41) and stearic acids (r2 = 0.52; RPD = 1.44) was too low for allowing their application in practice. NIRS discrimination of oil content and concentrations of oleic and linoleic acids was mainly based on the spectral region from 2240 to 2380 nm. Practical applications : NIRS is a high‐throughput analytical technique that allows fast measurement of several traits in a single analysis without using chemical reagents. We evaluated the feasibility of analyzing oil content and concentrations of palmitic, stearic, oleic, and linoleic acids in almond flour using fruits collected during 2 years from a world germplasm collection. The fruits collected in 2009 were used for NIRS calibration, whereas the fruits collected in 2010 were used for validation. NIRS equations were highly accurate for measuring oil content and concentrations of oleic and linoleic acids, which are important traits defining the quality of almond flour for specific uses in the food industry. These results have applications both in the research laboratory and the food industry, where NIRS is becoming a widely used technique for quality control. 相似文献
976.
977.
The structure, porosity and crystallization behavior of poly (L-lactic acid) and poly (L-lactic acid)/polyurethane porous membranes, prepared from ethanol/dioxane and ethanol/water coagulation baths through immersion precipitation, have been systematically investigated. The diffusion rate between solvent and nonsolvent as well as the equilibrium phase diagram of PLLA/solvent/nonsolvent system were also well studied. It has been proved that the ultimate structure and performance of the membranes could be mediated under control by suitable adjustment on phase separation behavior of the ternary system through varying coagulation bath compositions. The results show that the presence of lower ratio of dioxane in ethanol baths endows the resulting membranes with uniform sponge-like structure, higher porosity and crystallinity due to the moderate solidification and crystallization of PLLA, while increasing the water concentration tends to have a modestly opposite effect and obtains membranes with irregular finger-like structure, lower porosity and crystallinity. Under the same coagulation baths, PLLA/PU membranes possess slightly larger pores size and porosity than pure PLLA membranes, but the presence of PU appears to have no effect on the crystallinity of PLLA. 相似文献
978.
Sun‐Mou Lai Kun‐Che Hung Hui Cheng Kao Liang‐Chuan Liu Xue Fen Wang 《应用聚合物科学杂志》2013,130(4):2399-2409
The properties of metallocene polyethylene (mPE)/polylactic acid (PLA) bio‐based blends containing an ethylene‐glycidyl methacrylate‐vinyl acetate (EGMA‐VA) compatibilizer, with or without the annealing effect of PLA were investigated. The results from SEM (Scanning electron microscope) morphology observation revealed that the dispersed PLA particles sizes within the mPE matrix tended to decrease with the added compatibilizer due to the enhanced interfacial interaction. DSC (Differential scanning calorimetry) and XRD (X‐ray diffractometer) results indicated that the addition of the compatibilizer completely hindered the cold crystallization and rearrangement crystallization of PLA, even though the additional annealing effect tended to increase the crystallization of PLA. Tensile test results showed the synergistic effects by compatibilization and annealing treatment improved the tensile strength and Young's modulus, up to 38 % and 62 % increase, respectively. With the incorporation of the compatibilizer, the viscosity increased and reached the highest level among all neat resins and blends, which was attributed to the enhanced interfacial interaction between mPE and PLA. Hopefully, the incorporated bio‐based PLA materials could be helpful in reducing the use of petroleum‐based materials and are beneficial to the environment in terms of the sustainable development concern. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2399–2409, 2013 相似文献
979.
980.
For practical applications, especially in an organic-solution situation, the surface of TiO2 nanoparticles (NP)s requires modification with an organic coupling agent. Therefore, in this study, the surface of TiO2 NPs with average diameter of 30 nm was modified with bioactive dicarboxylic acids (DA)s containing different natural amino acids such as l-valine, l-methionine, l-leucine, and l-isoleucine. The prepared DAs-modified TiO2 NPs were studied with Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis techniques. The results showed that the modifiers were grafted on the surface of TiO2 NPs. Modified TiO2 NPs could be environmentally friendly due to the presence of bioactive DAs. 相似文献