共查询到20条相似文献,搜索用时 31 毫秒
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Matilde S. Rodrigues Samira G. Ferreira Csar Quiroz Christopher J. Earley Diego García-Borreguero Rodrigo A. Cunha Francisco Ciruela Attila Kfalvi Sergi Ferr 《Molecules (Basel, Switzerland)》2022,27(5)
Brain iron deficiency (BID) constitutes a primary pathophysiological mechanism in restless legs syndrome (RLS). BID in rodents has been widely used as an animal model of RLS, since it recapitulates key neurochemical changes reported in RLS patients and shows an RLS-like behavioral phenotype. Previous studies with the BID-rodent model of RLS demonstrated increased sensitivity of cortical pyramidal cells to release glutamate from their striatal nerve terminals driving striatal circuits, a correlative finding of the cortical motor hyperexcitability of RLS patients. It was also found that BID in rodents leads to changes in the adenosinergic system, a downregulation of the inhibitory adenosine A1 receptors (A1Rs) and upregulation of the excitatory adenosine A2A receptors (A2ARs). It was then hypothesized, but not proven, that the BID-induced increased sensitivity of cortico-striatal glutamatergic terminals could be induced by a change in A1R/A2AR stoichiometry in favor of A2ARs. Here, we used a newly developed FACS-based synaptometric analysis to compare the relative abundance on A1Rs and A2ARs in cortico-striatal and thalamo-striatal glutamatergic terminals (labeled with vesicular glutamate transporters VGLUT1 and VGLUT2, respectively) of control and BID rats. It could be demonstrated that BID (determined by measuring transferrin receptor density in the brain) is associated with a selective decrease in the A1R/A2AR ratio in VGLUT1 positive-striatal terminals. 相似文献
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Margherita Mastromarino Mauro Niso Carmen Abate Ewgenij Proschak Mariam Dubiel Holger Stark Marin Castro Enza Lacivita Marcello Leopoldo 《Molecules (Basel, Switzerland)》2022,27(4)
Long-chain arylpiperazine scaffold is a versatile template to design central nervous system (CNS) drugs that target serotonin and dopamine receptors. Here we describe the synthesis and biological evaluation of ten new arylpiperazine derivatives designed to obtain an affinity profile at serotonin 5-HT1A, 5-HT2A, 5-HT7 receptor, and dopamine D2 receptor of prospective drugs to treat the core symptoms of autism spectrum disorder (ASD) or psychosis. Besides the structural features required for affinity at the target receptors, the new compounds incorporated structural fragments with antioxidant properties to counteract oxidative stress connected with ASD and psychosis. All the new compounds showed CNS MultiParameter Optimization score predictive of desirable ADMET properties and cross the blood–brain barrier. We identified compound 12a that combines an affinity profile compatible with antipsychotic activity (5-HT1A Ki = 41.5 nM, 5-HT2A Ki = 315 nM, 5-HT7 Ki = 42.5 nM, D2 Ki = 300 nM), and compound 9b that has an affinity profile consistent with studies in the context of ASD (5-HT1A Ki = 23.9 nM, 5-HT2A Ki = 39.4 nM, 5-HT7 Ki = 45.0 nM). Both compounds also had antioxidant properties. All compounds showed low in vitro metabolic stability, the only exception being compound 9b, which might be suitable for studies in vivo. 相似文献
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《Analytical letters》2012,45(13):1071-1087
Abstract A nephelometric procedure for quantitative measurement of glycohemoglobin (Hb A1) was developed, evaluated, and compared with the semi-quantitative mini-column chromatographic procedure. Hb A1 was purified from human red cell hemolystate by Bio-Rex 70 ion-exchange liquid chromatography and was used for standards and immunization. The antisera raised in rabbits showed high cross-reactivities with normal human hemoglobin (Hb A). The latter was separated by mixing 25 μl of patients' hemolystate with 2 ml ion-exchange resin suspension for 15 minutes. One hundred microiters of the supernatant was incubated with 900 μl antiserum (dilution 1:50) for 45 minutes at room temperature. Samples were then read on a laser nephelometer. The sensitivity of the assay was found to be 0.1 mg Hb A1. The intraassay relative standard deviation (RSD) was 5.6% and the interassay RSD was 6.5%. 相似文献
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Stefania Merighi Pier Andrea Borea Katia Varani Fabrizio Vincenzi Alessia Travagli Manuela Nigro Silvia Pasquini R. Rama Suresh Sung Won Kim Nora D. Volkow Kenneth A. Jacobson Stefania Gessi 《Molecules (Basel, Switzerland)》2022,27(9)
The A2A adenosine receptor is a protein belonging to a family of four GPCR adenosine receptors. It is involved in the regulation of several pathophysiological conditions in both the central nervous system and periphery. In the brain, its localization at pre- and postsynaptic level in striatum, cortex, hippocampus and its effects on glutamate release, microglia and astrocyte activation account for a crucial role in neurodegenerative diseases, including Alzheimer’s disease (AD). This ailment is considered the main form of dementia and is expected to exponentially increase in coming years. The pathological tracts of AD include amyloid peptide-β extracellular accumulation and tau hyperphosphorylation, causing neuronal cell death, cognitive deficit, and memory loss. Interestingly, in vitro and in vivo studies have demonstrated that A2A adenosine receptor antagonists may counteract each of these clinical signs, representing an important new strategy to fight a disease for which unfortunately only symptomatic drugs are available. This review offers a brief overview of the biological effects mediated by A2A adenosine receptors in AD animal and human studies and reports the state of the art of A2A adenosine receptor antagonists currently in clinical trials. As an original approach, it focuses on the crucial role of pharmacokinetics and ability to pass the blood–brain barrier in the discovery of new agents for treating CNS disorders. Considering that A2A receptor antagonist istradefylline is already commercially available for Parkinson’s disease treatment, if the proof of concept of these ligands in AD is confirmed and reinforced, it will be easier to offer a new hope for AD patients. 相似文献
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Abstract With a 1:1 and a 2:1 host-guest stoichiometry, α-cyclodextrin (α-CD) forms inclusion complexes with 2-chloronaphthalene. From simulations concerning observed chemical-shift differences (Δδobs) of proton signals of 2-chloronaphthalene, intrinsic Δδ values are estimated for all the guest protons in the 1:1 and 2:1 inclusion complexes. The intrinsic Δδ values indicate that α-CD first binds to a part of a naphthalene ring bearing a C1 atom to form the 1:1 inclusion complex. In the 1:1 and 2:1 inclusion complexes, the symmetry axes of α-CD are tilted approximately 30° relative to a naphthalene longitudinal axis. In the 2:1 inclusion complex, the association through hydrogen bonding most likely occurs between two α-CD molecules whose symmetry axes are laterally shifted. 相似文献
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《合成通讯》2013,43(15):2605-2611
Abstract The o-nitrobenzyl group, possessing distinct advantage of being photolabile under mild conditions, was successfully connected to 8-(5,6-epoxynorbornan-2-yl)-1,3-dipropylxanthine (5), a high specific A1 adenosine receptor antagonist. The resulting compound 4 would have potential use as a prodrug. 相似文献
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Wang Y Yuan B Deng X He L Wang S Zhang Y Han Q 《Analytical and bioanalytical chemistry》2006,386(7-8):2003-2011
A G-protein-coupled receptor-cell-membrane stationary phase (CMSP) has been prepared by immobilizing cell membranes on the
surface of silica, as carrier. The resulting HEK293
α
1A
adrenoceptor cell-membrane stationary phase can be used for rapid on-line chromatographic determination of potential subtype-selective
α
1
-adrenoceptor ligand-binding affinities for α
1
-adrenoceptor subtypes. The objective of the research was to study whether cell lines stably overexpressing subtype receptors
could improve the sensitivity and specificity of cell-membrane chromatography (CMC) compared with use of homogenized tissue
and cells in primary culture. Effects of mobile-phase ionic strength, sample concentration, and the presence of competitive
agents on ligand-receptor interaction in CMSP were also evaluated. We found that cell lines stably overexpressing subtype
receptors led to improved sensitivity and specificity in CMC. The technique leads to useful procedures-cell-membrane stationary
phases may, for example, facilitate exploration of ligand-receptor interaction and determination of ligand-receptor binding
affinity in initial screening and separation of lead compounds or active components in Chinese traditional natural medicine
and herbs. This might eventually be an important contribution and an addition to our collection of techniques. 相似文献
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Xuesong Wang Willem Jespers Kim A. N. Wolff Jill Buytelaar Adriaan P. IJzerman Gerard J. P. van Westen Laura H. Heitman 《Molecules (Basel, Switzerland)》2022,27(12)
Overexpression of the adenosine A1 receptor (A1AR) has been detected in various cancer cell lines. However, the role of A1AR in tumor development is still unclear. Thirteen A1AR mutations were identified in the Cancer Genome Atlas from cancer patient samples. We have investigated the pharmacology of the mutations located at the 7-transmembrane domain using a yeast system. Concentration–growth curves were obtained with the full agonist CPA and compared to the wild type hA1AR. H78L3.23 and S246T6.47 showed increased constitutive activity, while only the constitutive activity of S246T6.47 could be reduced to wild type levels by the inverse agonist DPCPX. Decreased constitutive activity was observed on five mutant receptors, among which A52V2.47 and W188C5.46 showed a diminished potency for CPA. Lastly, a complete loss of activation was observed in five mutant receptors. A selection of mutations was also investigated in a mammalian system, showing comparable effects on receptor activation as in the yeast system, except for residues pointing toward the membrane. Taken together, this study will enrich the view of the receptor structure and function of A1AR, enlightening the consequences of these mutations in cancer. Ultimately, this may provide an opportunity for precision medicine for cancer patients with pathological phenotypes involving these mutations. 相似文献
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A novel selective and sensitive colorimetric receptor 1 (1, 10-phenanthroline-2, 9-dialdehyde bis-(-p-nitrophenylureasemicarbo-hydrazone)) based on urea showing distinctive color fading phenomenon towards H2PO4? ion was reported. Fancifully, the recognition process of receptor 1 to H2PO4? was not interfered by the existence of others anions. We have probed the binding mechanism of 1-H2PO4? that H2PO4? ion induced competitive hydrogen binding process via intramolecular hydrogen-bond by UV–vis, fluorescence, 1H NMR titrations and ESI-MS experiments. 相似文献
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In this comment to a recent paper [Anal. Chim. Acta 585 (2007) 241-245], we report a comparison study on Mn oxide-related compounds with different crystallographic forms, which distinguish between β-MnO2 and α-MnO2 type materials via Raman scattering (RS) spectroscopy. The tetragonal rutile-type β-MnO2 is characterized by a RS band at ∼667 cm−1 of symmetry A1g, whereas the α-MnO2 type materials feature two main RS contributions at about 574 and 634 cm−1, belonging to Ag spectroscopic species of a tetragonal hollandite-type framework. These data represent a clear signature for identifying β-MnO2 and α-MnO2 type materials via RS spectroscopy. 相似文献
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Kanhokthron Boonkitpattarakul Darunee Soorukram Patoomratana Tuchinda Vichai Reutrakul Manat Pohmakotr 《Journal of fluorine chemistry》2011,132(11):987-990
The synthetic utility of α,α-difluoro-α-phenylsulfanyl-α-trimethylsilylmethane (PhSCF2SiMe3; 1) as a difluoromethyl building block providing a general strategy to α,α-difluoromethyl aryl ketones was demonstrated. Oxidation, by using m-chloroperoxybenzoic acid, of the readily available 1-aryl-2,2-difluoro-2-phenylsulfanyl-1-trimethylsiloxyethanes obtained from fluoride-catalyzed nucleophilic addition of PhSCF2SiMe3 with aromatic aldehydes followed by flash vacuum pyrolytic elimination provided α,α-difluoromethyl aryl ketones in moderate overall yields. 相似文献
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Yiman Guo Toru Uyama S. M. Khaledur Rahman Mohammad Mamun Sikder Zahir Hussain Kazuhito Tsuboi Minoru Miyake Natsuo Ueda 《Molecules (Basel, Switzerland)》2021,26(17)
Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other N-acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via N-acyl-phosphatidylethanolamine (NAPE). The ɛ isoform of cytosolic phospholipase A2 (cPLA2) functions as an N-acyltransferase to form NAPE. Since the cPLA2 family consists of six isoforms (α, β, γ, δ, ɛ, and ζ), the present study investigated a possible involvement of isoforms other than ɛ in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA2 isoforms were labeled with [14C]ethanolamine, the increase in the production of [14C]NAPE was observed only with the ɛ-expressing cells. Secondly, when the cells co-expressing ɛ and one of the other isoforms were analyzed, the increase in [14C]N-acyl-lysophosphatidylethanolamine (lysoNAPE) and [14C]NAE was seen with the combination of ɛ and γ isoforms. Furthermore, the purified cPLA2γ hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-N-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA2γ is involved in the biosynthesis of NAE by its phospholipase A1/A2 and lysophospholipase activities. 相似文献
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《Analytical letters》2012,45(2):187-201
Abstract The synthesis of tetradeuterated 15-methyl-PGF2α and 17-phenyl-18, 19, 20-trinor-PGF2α, is described. Gas chromatographic -mass spectrometric methods, using the deuterated compounds as internal standards and carriers, for quantitation of corresponding unlabeled prostaglandin analogues is described. With acceptable accuracy and precision the sensitivity is in the subpicomole range. 相似文献
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α-Fe2O3 nanorods were incorporated into poly(methyl methacrylate) (PMMA) by in situ radical polymerisation of methyl methacrylate initiated by 2,2′-azobisisobutyronitrile. The α-Fe2O3 nanorods were synthesized by forced hydrolysis of FeCl3 and structural characterization was performed by X-ray diffraction and transmission electron microscopy. The molar mass and the polydispersity index of synthesized PMMA samples were determined by gel permeation chromatography. The content of residual monomer was determined by 1H NMR spectroscopy. The influence of α-Fe2O3 nanorods on the thermal stability of the polymer was investigated using thermogravimetry and differential scanning calorimetry. The molar mass and polydispersity index of PMMA were dependent on the content of α-Fe2O3 nanorods. The values of the glass transition temperature of the nanocomposites were lower compared to pure PMMA. Also, the thermal stability of nanocomposites in nitrogen and air was different from that of pure PMMA. 相似文献
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Upon being brought into contact with each other, α-Cu2Se and α-CuSe pellets reacted entirely forming Cu3Se2 at room temperature. After 10 days, the reaction was almost completed. Weight measurements revealed that copper atoms migrated from α-Cu2Se to α-CuSe. Solid-state reactions were also observed in the (α-Cu2Se+Cu3Se2) and (α-Cu2Se+CuS) systems, but not in the (Cu3Se2+α-CuSe), (Cu2S+CuS) and (α-CuSe+Cu2S) systems. Therefore, the high ionic conductivity of copper ions in α- and β-Cu2Se is considered to be responsible for the solid-state reactions observed in these systems. 相似文献
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《Analytical letters》2012,45(6):537-542
Abstract An enzymatic determination of urinary 7α-hydroxy bile acids is described. The principle of the method is as follows: after hydrolysis with β-glucuronidase and solvolysis, the ethyl acetate extract is washed with alkalin solution and water, then the alkali and water washes of the ethyl acetate extract are combined and the solution is acidified to pH 1 and sodium chloride added. Shake solution with ethyl acetate to re-extract the acidic fraction and the ethyl acetate layer is evaporated. Add enzyme color solution of 7α-hydroxysteroid dehydrogenase (7α-HSD, from E. coli) to a tube of extract residue and then after incubation, measure the absorbance of the solution. Excretion values of urinary total 7α-hydroxy bile acids was measured with patients of acute hepatitis and normal subjects and excretion pattern of 7α-hydroxy bile acids by the use of chromatographic fractionation was also shown. 相似文献
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Kandula Madhu Kumar Reddy Sarva Santhisudha Gundluru Mohan Kotha Peddanna Chippada Appa Rao 《Phosphorus, sulfur, and silicon and the related elements》2016,191(6):933-938
A one pot three-component nano Gd2O3 catalyzed neat reaction of 2-morpholinoethanamine and dimethylphosphite with various salicylaldehydes under microwave irradiation afforded a series of new α-aminophosphonates in high yields. The synthesized compounds were characterized by FT-IR, (1H, 13C, 31P)-NMR, and mass spectral methods. The antioxidant activity of these compounds was evaluated against DPPH, NO, and H2O2 methods and found that the compound Dimethyl (2-hydroxy-5-nitrophenyl) (2-morpholinoethylamino) methylphosphonate (4h) has higher antioxidant activity than the corresponding standards. 相似文献