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91.
Arpita Dey Ran Chen Feng Li Subhamita Maitra Jean-Francois Hernandez Guo-Chun Zhou Bruno Vincent 《Molecules (Basel, Switzerland)》2021,26(24)
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aβ) in the brain. Whereas β-secretase supports Aβ formation along the amyloidogenic processing of the β-amyloid precursor protein (βAPP), α-secretase counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting β-secretase can be considered a promising anti-AD therapeutic track. In this context, we tested andrographolide, a labdane diterpene derived from the plant Andrographis paniculata, as well as 24 synthesized derivatives, for their ability to induce sAPPα production in cultured SH-SY5Y human neuroblastoma cells. Following several rounds of screening, we identified three hits that were subjected to full characterization. Interestingly, andrographolide (8,17-olefinic) and its close derivative 14α-(5′,7′-dichloro-8′-quinolyloxy)-3,19-acetonylidene (compound 9) behave as moderate α-secretase activators, while 14α-(2′-methyl-5′,7′-dichloro-8′-quinolyloxy)-8,9-olefinic compounds 31 (3,19-acetonylidene) and 37 (3,19-diol), whose two structures are quite similar although distant from that of andrographolide and 9, stand as β-secretase inhibitors. Importantly, these results were confirmed in human HEK293 cells and these compounds do not trigger toxicity in either cell line. Altogether, these findings may represent an encouraging starting point for the future development of andrographolide-based compounds aimed at both activating α-secretase and inhibiting β-secretase that could prove useful in our quest for the therapeutic treatment of AD. 相似文献
92.
93.
A class of zero-sum, two-person stochastic games is shown to have a value which can be calculated by transfinite iteration
of an operator. The games considered have a countable state space, finite action spaces for each player, and a payoff sufficiently
general to include classical stochastic games as well as Blackwell’s infiniteG
δ games of imperfect information.
Research supported by National Science Foundation Grants DMS-8801085 and DMS-8911548. 相似文献
94.
A continuous-flow system is reported for the determination of horseradish peroxidase (HRP) with a fluoride-selective electrode. Reaction conditions are optimized for the HRP-catalysed oxidation of p-fluoroaniline (0.104 M) with hydrogen peroxide (4.0 mM) as the oxidant in 0.16 M acetate buffer at pH 4.6. HRP is determined in the concentration range 0.016–0.12 U ml?1 in the flow system at a sampling rate of 24 h?1. Interfering effects caused by known HRP inhibitors, including metal ions, cyanide and sulphide, are reported for the range 1 μM–1 mM. Applications of the system for determination of the enzyme in turnip extract and milk are described. 相似文献
95.
96.
We prove that a two-person, zero-sum stochastic game with arbitrary state and action spaces, a finitely additive law of motion
and a bounded Borel measurable payoff has a value.
Received December 1996/Final version November 1997 相似文献
97.
A newchola lariat ether (1, a 21-crown-6) was constructed fromreadily available precursors. The association constant of compound1 with alkali metal picrates was measured using Cram’s extraction protocol. Evidence is presented for the involvement of the
3-methoxy group for the complexation. Energy minimised structures show that the A-ring gets slightly distorted upon metal
ion binding.
Dedicated to Professor C N R Rao on his 70th birthday 相似文献
98.
17-Chlorosteroids from template-directed halogenation can be converted to 17(20) olefins with DBU or DBN. The dependence of this reaction on base-structure and reaction conditions suggests geometric control by liquid packing effects related to those operating in liquid crystals. 相似文献
99.
The aggregation properties of novel bile acid analogs-phosphonobile salts (PBS)-have been studied. The critical micellar concentration of 23 and 24-phosphonobile salts were measured using fluorescence and 31P NMR methods. All the ten synthesized phosphonobile salts formed gels at different pH ranges in water. The pH range at which individual PBSs could gelate water was narrow and influenced by the number and conformation of hydroxyl groups. A reversible thermochromic system has been developed (with 23-phosphonodeoxycholate at pH 3.3), which changes color upon gelation. The investigation of the first hydrogels derived from trihydroxy bile acid analogs 1 and 6 was made using fluorescence, 31P NMR, X-ray crystallography, circular dichroism and SEM. The present studies reveal that the gel network consists of a chiral, fibrous structure possessing hydrophobic interiors. 相似文献
100.
Maitra NT 《The Journal of chemical physics》2005,122(23):234104
Long-range charge-transfer excited states are notoriously badly underestimated in time-dependent density-functional theory (TDDFT). We discuss how exact TDDFT captures charge transfer between open-shell species: in particular, the role of the step in the ground-state potential, and the severe frequency dependence of the exchange-correlation kernel. An expression for the latter is derived, that becomes exact in the limit that the charge-transfer excitations are well separated from other excitations. The exchange-correlation kernel has the task of undoing the static correlation in the ground state introduced by the step, in order to accurately recover the physical charge-transfer states. 相似文献