Neuraminidase activity is essential for the infection and propagation of paramyxoviruses, including human parainfluenza viruses (hPIVs) and the Newcastle disease virus (NDV). Thus, many inhibitors have been developed based on the 2‐deoxy‐2,3‐didehydro‐d ‐N‐acetylneuraminic acid inhibitor (DANA) backbone. Along this line, herein we report a series of neuraminidase inhibitors, having C4 (p‐toluenesulfonamido and azido substituents) and C5 (N‐perfluorinated chains) modifications to the DANA backbone, resulting in compounds with 5‐ to 15‐fold greater potency than the currently most active compound, the N‐trifluoroacetyl derivative of DANA (FANA), toward the NDV hemagglutinin‐neuraminidase (NDV‐HN). Remarkably, these inhibitors were found to be essentially inactive against the human sialidase NEU3, which is present on the outer layer of the cell membrane and is highly affected by the current NDV inhibitor FANA. 相似文献
The quinoline‐5,8 dicarboxylic acid scaffold has been identified by a fragment‐based approach as new potential lead compound for the development of JMJD3 inhibitors. Among them, 3‐(2,4‐dimethoxypyrimidin‐5‐yl)quinoline‐5,8‐dicarboxylic acid (compound 3 ) shows low micromolar inhibitory activity against Jumonji domain‐containing protein 3 (JMJD3). The experimental evaluation of inhibitory activity against seven related isoforms of JMJD3 highlighted an unprecedented selectivity toward the biological target of interest. 相似文献
Within the actinide and lanthanide co-extraction strategy, three rigidified diglycolamides, namely 2,6-bis (N-dodecyl-carboxamide)-4-oxo-4H-pyran (1), 2,6-bis-[N-(4-tert-butylphenyl)carboxamide]-4-oxo-4H-pyran (2), 2,6-?bis[(N-docecyl-N-methyl)carboxamide]-?4-methoxy-?tetrahydro-pyran (3), were synthesized. Moreover, the effect of structural rigidification on Am(III) and Eu(III) extraction under different conditions was investigated. The carboxamide extractant 3 resembles the extracting behavior of N,N,N′,N′‐tetraoctyl diglycolamide (TODGA) in terms of efficiency and affinity within the lanthanide family, together with fast kinetics and satisfactory cation back-extraction. The presence of 1-octanol in the diluent mixture strongly affects the ligand stability. Moreover, despite the low extraction efficiency showed by 1 and 2, all the three ligands exhibit a higher affinity for Am with respect to TODGA, resulting in a lower lanthanide/Americium separation factor, of around 4 for ligand 3 and close to 1 for ligands 1 and 2. 相似文献
The Virgo interferometer, aimed at detecting gravitational waves, is now in a commissioning phase. Measurements of its optical properties are needed for the understanding of the instrument. We present the techniques developed for the measurement of the optical parameters of Virgo. These parameters are compared with the Virgo specifications. 相似文献
Multitarget therapeutic leads for Alzheimer’s disease were designed on the models of compounds capable of maintaining or restoring cell protein homeostasis and of inhibiting β‐amyloid (Aβ) oligomerization. Thirty‐seven thioxanthen‐9‐one, xanthen‐9‐one, naphto‐ and anthraquinone derivatives were tested for the direct inhibition of Aβ(1–40) aggregation and for the inhibition of electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBChE). These compounds are characterized by basic side chains, mainly quinolizidinylalkyl moieties, linked to various bi‐ and tri‐cyclic (hetero)aromatic systems. With very few exceptions, these compounds displayed inhibitory activity on both AChE and BChE and on the spontaneous aggregation of β‐amyloid. In most cases, IC50 values were in the low micromolar and sub‐micromolar range, but some compounds even reached nanomolar potency. The time course of amyloid aggregation in the presence of the most active derivative (IC50=0.84 μM ) revealed that these compounds might act as destabilizers of mature fibrils rather than mere inhibitors of fibrillization. Many compounds inhibited one or both cholinesterases and Aβ aggregation with similar potency, a fundamental requisite for the possible development of therapeutics exhibiting a multitarget mechanism of action. The described compounds thus represent interesting leads for the development of multitarget AD therapeutics. 相似文献
Background: Nanotechnology is a promising area in industry with a broad range of applications including in the agri-food sector. Several studies have investigated the potential benefits deriving from use of nanomaterials in the context of the whole food chain drawing scenarios of benefits but also potential for concerns. Among the agri-food sector, animal production has potential for nanomaterial application but also for safety concerns due to the possibility of nanomaterial accumulation along the farm-to-fork path.
Scope and Approach: The aim of this work was to define the state of the art of nanomaterial applications in the animal production sector by assessing data belonging to recently publishes studies. To do this, a qualitative synthesis approach was applied to build a fit-for-purpose framework and to summarise relevant themes in the context of effectiveness, feasibility and health concerns.
Key findings and conclusions: Nanomaterials have potential for use in a wide range of applications from feed production and farming to food packaging, including several detection tools designed for the benefit of consumer protection. The current high degree of variability in nanomaterials tested and in study designs impairs external validation of research results. Further research is required to clearly define which safe nanomaterial applications have the potential to reach the market. 相似文献
The aim of this study as a part of the food traceability project “TRACE” funded by the EU was to investigate if honeys produced in regions with different climatic and geological characteristics could be discriminated on the basis of the isotopic data. The hydrogen, carbon, nitrogen and sulphur stable isotope ratios of 516 authentic honeys from 20 European regions are presented and discussed. As honey contains only small quantities of nitrogen and sulphur, the honey protein was precipitated in order to obtain measurable amounts of these elements. The mean hydrogen isotopic ratios of the honey protein were found to be significantly correlated with the mean hydrogen isotopic ratios of precipitation and groundwater in the production regions. Carbon isotopic ratios were influenced by climate. The sulphur stable isotope composition is clearly influenced by geographical location (sea spray effect) and surface geology of the production regions. The results show that the stable isotope ratios of the four bio-elements carbon, nitrogen, hydrogen and sulphur in honey protein can be applied to verify the origin of honey. Carbon and sulphur were identified by canonical discriminant analysis as providing the maximum discrimination between honey samples. For seven regions the percentage of correct classified samples is greater than 70%. It was concluded that the methodology in its current state can be used to provide reliable origin information. 相似文献