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91.
Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids 下载免费PDF全文
Mohamed Benchekroun Dr. Manuela Bartolini Dr. Javier Egea Dr. Alejandro Romero Dr. Elena Soriano Dr. Marc Pudlo Vincent Luzet Prof. Vincenza Andrisano Dr. María‐Luisa Jimeno Dr. Manuela G. López Sarah Wehle Prof. Tijani Gharbi Prof. Bernard Refouvelet Lucía de Andrés Clara Herrera‐Arozamena Prof. Barbara Monti Prof. Maria Laura Bolognesi Prof. María Isabel Rodríguez‐Franco Prof. Dr. Michael Decker Prof. José Marco‐Contelles Dr. Lhassane Ismaili 《ChemMedChem》2015,10(3):523-539
Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC50=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ1–40, Aβ1–42, H2O2, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease. 相似文献
92.
Kazadi N. Mutoji Mingxia Sun Garrett Elliott Isabel Y. Moreno Clare Hughes Tarsis F. Gesteira Vivien J. Coulson-Thomas 《International journal of molecular sciences》2021,22(11)
Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of glycosaminoglycans (GAGs) and PGs after a chemical injury. The chemical composition of chondroitin sulfate (CS)/dermatan sulfate (DS) and heparan sulfate (HS) were characterized in mouse corneas 5 and 14 days after alkali burn (AB), and compared to uninjured corneas. The expression profile and corneal distribution of CS/DSPGs and keratan sulfate (KS) PGs were also analyzed. We found a significant overall increase in CS after AB, with an increase in sulfated forms of CS and a decrease in lesser sulfated forms of CS. Expression of the CSPGs biglycan and versican was increased after AB, while decorin expression was decreased. We also found an increase in KS expression 14 days after AB, with an increase in lumican and mimecan expression, and a decrease in keratocan expression. No significant changes in HS composition were noted after AB. Taken together, our study reveals significant changes in the composition of the extracellular matrix following a corneal chemical injury. 相似文献
93.
Isabel Pagani Pietro Demela Silvia Ghezzi Elisa Vicenzi Massimo Pizzato Guido Poli 《International journal of molecular sciences》2022,23(6)
In addition to CD4+ T lymphocytes, myeloid cells and, particularly, differentiated macrophages are targets of human immunodeficiency virus type-1 (HIV-1) infection via the interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication, although with substantial differences. In contrast to activated CD4+ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by the virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing or curtailing virus replication in macrophages and T cells, particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factors determining the restriction or reactivation of virus replication in these cells. 相似文献
94.
Ana Isabel Gonzlez-Hernndez Loredana Scalschi Begonya Vicedo Emilio Luis Marcos-Barbero Rosa Morcuende Gemma Camaes 《International journal of molecular sciences》2022,23(6)
Putrescine (Put) is the starting point of the polyamines (PAs) pathway and the most common PA in higher plants. It is synthesized by two main pathways (from ornithine and arginine), but recently a third pathway from citrulline was reported in sesame plants. There is strong evidence that Put may play a crucial role not only in plant growth and development but also in the tolerance responses to the major stresses affecting crop production. The main strategies to investigate the involvement of PA in plant systems are based on the application of competitive inhibitors, exogenous PAs treatments, and the most efficient approaches based on mutant and transgenic plants. Thus, in this article, the recent advances in understanding the role of this metabolite in plant growth promotion and protection against abiotic and biotic stresses will be discussed to provide an overview for future research. 相似文献
95.
Lamb loins were subjected to sous-vide cooking at different combinations of temperature (60, 70, and 80 °C) and time (6, 12, and 24 h). Different physicochemical, histological and structural parameters were studied. Increasing cooking temperatures led to higher weight losses and lower moisture contents, whereas the effect of cooking time on these variables was limited. Samples cooked at 60 °C showed the highest lightness and redness, while increasing cooking temperature and cooking time produced higher yellowness values. Most textural variables in a texture profile analysis showed a marked interaction between cooking temperature and time. Samples cooked for 24 h showed significantly lower values for most of the studied textural parameters for all the temperatures considered. Connective tissue granulation at 60 °C and gelation at 70 °C were observed in the SEM micrographs. The sous-vide cooking of lamb loins dramatically reduced microbial population even with the less intense heat treatment studied (60 °C–6 h). 相似文献
96.
97.
Ferran V. García-Ferrer Isabel Pérez-Arjona Germán J. de Valcárcel Eugenio Roldán 《Journal of Modern Optics》2013,60(5):763-773
It is well known that the squeezing spectrum of the field exiting a nonlinear cavity can be directly obtained from the fluctuation spectrum of normally ordered products of creation and annihilation operators of the cavity mode. In this article we show that the output field squeezing spectrum can be derived also by combining the fluctuation spectra of any pair of s -ordered products of creation and annihilation operators. The interesting result is that the spectrum obtained in this way from the linearized Langevin equations is exact, and this occurs in spite of the fact that no s -ordered quasiprobability distribution verifies a true Fokker–Planck equation; that is, the Langevin equations used for deriving the squeezing spectrum are not exact. The (linearized) intracavity squeezing obtained from any s -ordered distribution is also exact. These results are exemplified in the problem of dispersive optical bistability. 相似文献
98.
“Castelo Branco” cheese is a Portuguese DOP cheese made from raw ewe’s milk coagulated with Cynara cardunculus, ripened for at least 40 days. “Merino da Beira Baixa” pure race is frequently used to produce milk for this cheese, however, exotic races such as Assaf and crusade of these two races are also used. The aim of this work has been to compare the volatile profile and sensory characteristics of DOP “Castelo Branco” cheeses manufactured during winter season with milk of breeds from Merino, Assaf and crusade of these two races and identify volatile compounds that can distinguish these cheeses. 相似文献
99.
Maria Clariana Isabel D��az Carmen S��rraga Jose A. Garc��a-Regueiro 《Food Analytical Methods》2011,4(4):465-474
The analysis of eight cholesterol oxidation products: 7α–hydroxycholesterol, 7β–hydroxycholesterol, α–epoxycholesterol, β–epoxycholesterol,
20α–hydroxycholesterol, cholestanetriol, 25–hydroxycholesterol, and 7–ketocholesterol in dry–cured shoulder was carried out.
The extraction of lipids was performed by using the Bligh and Dyer method (1959). Interferences were removed by solid-phase extraction (SPE) in two steps with silica and aminipropylsilica SPE columns.
The separation of the eight cholesterol oxidation products was done by gas chromatography, and the detection was performed
by flame ionization detection (FID) and mass spectrometry (MS). The results obtained from the use of both systems of detection
were compared. The results showed that gas chromatography-mass spectrometry (GC–MS) was the most suitable technique to obtain
reliable quantitative data, and significant differences (p < 0.05) between FID and MS determining 7α–hydroxycholesterol, 20α–hydroxycholesterol, and 25–hydroxycholesterol were observed.
For the determination of cholesterol oxidation products, it was necessary to apply gas chromatography-tandem mass spectrometry
to increase the sensitivity and to avoid interference from other compounds. 相似文献
100.
Isabel Escriche Mircea Oroian Mario Visquert María L. Gras Daniel Vidal 《International Journal of Food Properties》2016,19(11):2575-2586
This study evaluated the rheological behavior of Burkina Faso honey and the use of exponential and polynomial models to predict the influence of chemical composition and temperature on the viscoelastic parameters: complex viscosity (η*) and loss modulus (G’’). Samples were first characterized by evaluating: water activity, 5-hydroxy methyl furfural, sugars (fructose, glucose, and sucrose), electrical conductivity, moisture, and color. Dynamic rheological properties were obtained at different temperatures (5, 10, 15, 20, 25, 30, and 40°C). All the honeys displayed Newtonian behavior. Complex viscosity and loss modulus can be predicted based on the chemical composition and temperature using polynomial models (R2 > 98.00%). 相似文献