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排序方式: 共有260条查询结果,搜索用时 15 毫秒
71.
Rosa Purgatorio Nicola Gambacorta Francesco Samarelli Gianfranco Lopopolo Modesto de Candia Marco Catto Orazio Nicolotti Cosimo D. Altomare 《Molecules (Basel, Switzerland)》2022,27(13)
The rational discovery of new peptidomimetic inhibitors of the coagulation factor Xa (fXa) could help set more effective therapeutic options (to prevent atrial fibrillation). In this respect, we explored the conformational impact on the enzyme inhibition potency of the malonamide bridge, compared to the glycinamide one, as a linker connecting the P1 benzamidine anchoring moiety to the P4 aryl group of novel selective fXa inhibitors. We carried out structure–activity relationship (SAR) studies aimed at investigating para- or meta-benzamidine as the P1 basic group as well as diversely decorated aryl moieties as P4 fragments. To this end, twenty-three malonamide derivatives were synthesized and tested as inhibitors of fXa and thrombin (thr); the molecular determinants behind potency and selectivity were also studied by employing molecular docking. The malonamide linker, compared to the glycinamide one, does significantly increase anti-fXa potency and selectivity. The meta-benzamidine (P1) derivatives bearing 2′,4′-difluoro-biphenyl as the P4 moiety proved to be highly potent reversible fXa-selective inhibitors, achieving inhibition constants (Ki) in the low nanomolar range. The most active compounds were also tested against cholinesterase (ChE) isoforms (acetyl- or butyrylcholinesterase, AChE, and BChE), and some of them returned single-digit micromolar inhibition potency against AChE and/or BChE, both being drug targets for symptomatic treatment of mild-to-moderate Alzheimer’s disease. Compounds 19h and 22b were selected as selective fXa inhibitors with potential as multimodal neuroprotective agents. 相似文献
72.
Summary: The solubilization and encapsulation of the weakly soluble protein hemoglobin was investigated at the nanoscale using self-assembly with the branched polymer polyethyleneimine (PEI), the lipid glycerol monooleate (GMO), and two amphiphilic poly(ethylenglycol) monooleate derivatives with molecular weights 2100 g/mol (MO-PEG1) and 860 g/mol (MO-PEG2). The created self-assembly nanovehicles were analyzed by quasi-elastic light scattering (QELS) in order to determine their sizes as well as by circular dichroism in order to characterize the protein presence in the nanoobjects. The cationic polymer PEI formed mixed nano-objects with the protein hemoglobin. The polymer conformation in the nanovehicle was established to be sensitive to dilution, a property that can be essential for the protein release upon administration. The amphiphile MO-PEG1 was a co-surfactant in the dispersion of monoglyceride lipid nanoobjects needed for the hemoglobin encapsulation. The amphiphile MO-PEG2 formed small micelles in the absence of a lipid. The nanoobjects dispersions were studied for their stability on storage and reproducibility. 相似文献
73.
Fiorentino A D'Abrosca B Pacifico S Izzo A D'Angelo G Monaco P 《Natural product communications》2010,5(10):1539-1542
Two new clerodane diterpenes were isolated from roots of Carex distachya Desf., a perennial plant widely distributed in the coastal area of the Mediterranean basin. Chemical characterization of the metabolites was carried out mainly by 1D and 2D NMR spectroscopy. The isolated compounds influenced either positively or negatively the plant growth (root and shoot elongation) of three coexisting herbaceous species. 相似文献
74.
Vladimir V. Baranov Maria M. Antonova Valentina A. Karnoukhova Angelina N. Kravchenko 《Tetrahedron letters》2017,58(23):2203-2205
An unexpected reductive transformation of 1-substituted 5-hydroxy-4,5-diphenyl-1H-imidazol-2(5H)-ones (imidazolones) and their cyclic analogs to give 1-substituted 4,5-diphenyl-1H-imidazol-2(5H)-ones (imidazolinones) upon reaction with thiourea and hydrochloric acid was discovered. 相似文献
75.
Graham Kendall Ruibin Bai Jacek Błazewicz Patrick De Causmaecker Michel Gendreau Robert John Jiawei Li Barry McCollum Erwin Pesch Rong Qu Nasser Sabar Greet Vanden Berghe Angelina Yee 《The Journal of the Operational Research Society》2016,67(4):676-689
Good Laboratory Practice has been a part of non-clinical research for over 40 years. Optimization Research, despite having many papers discussing standards being published over the same period of time, has yet to embrace standards that underpin its research. In this paper we argue the need to adopt standards in optimization research. Building on previous papers, many of which have suggested that the optimization research community should adopt certain standards, we suggest a concrete set of recommendations that the community should adopt. We also discuss how the proposals in this paper could be progressed. 相似文献
76.
A. Altomare C. Carlini F. Ciardelli R. Solaro N. Rosato 《Journal of polymer science. Part A, Polymer chemistry》1984,22(6):1267-1280
Copolymers of trans-4-acryloxyazobenzene ( AAB ) with (?)-menthyl acrylate ( MtA ) have been prepared by free radical initiation; comonomer reactivity ratios have been found to be r AAB = 0.89 and r MtA = 0.53. Dependence of chiroptical properties on copolymer composition has been investigated and contribution to circular dichroism by azobenzene chromophores of isolated and sequence AAB units, as well as the influence of the trans to cis photoisomerization, have been determined. Kinetics of photoinduced trans → cis and thermally induced cis → trans isomerization of azobenzene side chains have also been examined and the kinetic parameters evaluated with relation to copolymer structure. The results have been discussed in terms of light-induced secondary structure reversible modifications. 相似文献
77.
78.
Licia Pantano Giovanni Lo Cascio Angelina Alongi Antonio Vella Andrea Macaluso 《Natural product research》2016,30(20):2378-2382
A gas chromatographic with flame ionization detector (GC-MS FID) method for the identification and quantification of fatty acids based on the extraction of lipids and derivatisation of free acids to form methyl esters was developed and validated. The proposed method was evaluated to a number of standard FAs, and Bronte pistachios samples were used for that purpose and to demonstrate the applicability of the proposed method. In this regard, repeatability, mean and standard deviation of the analytical procedure were calculated. The results obtained have demonstrated oleic acid as the main component of Bronte pistachios (72.2%) followed by linoleic acid (13.4%) and showed some differences in composition with respect to Tunisian, Turkish and Iranian pistachios. 相似文献
79.
A novel LC-fluorescence detection method based on the use of a monolithic column for the determination of norfloxacin, ciprofloxacin, and enrofloxacin antibiotic residues in environmental waters was developed. Fluoroquinolones (FQs) were isocratically eluted using a mobile phase consisting of 0.025 M phosphoric acid solution at pH 3.0 with tetrabutylammonium and methanol (960:40, v/v) through a Chromolith Performance RP-18e column (100x4.6 mm) at a flow rate of 2.5 mL/min and detected at excitation and emission wavelengths of 278 and 450 nm, respectively. After acidification and addition of EDTA, water samples were extracted using an Oasis HLB cartridge. Linearity was evaluated in the range of 0.05 to 1 microg/mL and correlation coefficients of 0.9945 for norfloxacin, 0.9974 for ciprofloxacin, and 0.9982 for enrofloxacin were found. The limit of quantification was 25 ng/L for the three FQs. The recovery of FQs spiked into river water samples at 25, 50, and 100 ng/L fortification levels ranged from 76.5 to 91.0% for norfloxacin, 78.5 to 97.2% for ciprofloxacin, and 79.4 to 93.6% for enrofloxacin. This method was successfully applied to the analysis of water samples from the Mondego River, and ciprofloxacin and enrofloxacin residues were detected in eight water samples. 相似文献
80.