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121.
This work aims at studying the optimization of an on‐line capillary electrophoresis (CE)‐based tryptic digestion methodology for the analysis of therapeutic polypeptides (PP). With this methodology, a mixture of surrogate peptide fragments and amino acid were produced on‐line by trypsin cleavage (enzymatic digestion) and subsequently analyzed using the same capillary. The resulting automation of all steps such as injection, mixing, incubation, separation and detection minimizes the possible errors and saves experimental time. In this paper, we first study the differents parameters influencing PP cleavage inside the capillary (plug length, reactant concentration, incubation time, diffusion and electrophoretic plugs mixing). In a second part, the optimization of the electrophoretic separation conditions of generated hydrolysis products (nature, pH and ionic strength (I) of the background electrolyte (BGE)) is described. Using the optimized conditions, excellent repeatability was obtained in terms of separation (migration times) and proteolysis (number of products from enzymatic hydrolysis and corresponding amounts) demonstrating the robustness of the proposed methodology. 相似文献
122.
Reactivity of N,N″‐1,ω‐alkanediyl‐bis‐[N′‐organylthiourea] Derivatives Towards Isatylidene Malononitrile
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Alaa A. Hassan Kamal M. A. El‐Shaieb Amal S. Abd El‐Aal Stefan Bräse Martin Nieger 《Journal of heterocyclic chemistry》2016,53(6):2025-2029
(Z)‐2‐(2‐Oxoindolin‐3‐ylidene)‐2‐(substituted amino)acetonitriles, 2‐thioxoimidazolidine‐1‐carbothioamides, and 2‐thioxotetrahydropyrimidine‐1(2H)‐carbothioamides were synthesized via conventional thermal or microwave‐assisted reaction of isatylidene malononitrile with N,N″‐1,ω‐alkanediyl‐bis‐[N′‐organylthiourea] derivatives. Rationale for these conversations involving the nucleophilic addition on the dicyanomethylene carbon atom and intramolecular heterocyclization of the title compounds is presented. The structure of the (Z)‐2‐(2‐oxoindolin‐3‐ylidene)‐2‐(phenylamino)acetonitrile has been confirmed by the X‐ray analysis. 相似文献
123.
Ashraf N. Abdalla Waleed H. Malki Amal Qattan Imran Shahid Mohammad Akbar Hossain Muhammad Ahmed 《Molecules (Basel, Switzerland)》2021,26(2)
Colorectal cancer (CRC) remains one of the main causes of death worldwide and in Saudi Arabia. The toxicity and the development of resistance against 5 fluorouracil 5FU pose increasing therapeutic difficulties, which necessitates the development of personalized drugs and drug combinations. Objectives: First, to determine the most important kinases and kinase pathways, and the amount of ABC transporters and KRAS in samples taken from Saudi CRC patients. Second, to investigate the chemosensitizing effect of LY294002 and HAA2020 and their combinations with 5FU on HT29, HT29-5FU, HCT116, and HCT116-5FU CRC cells, their effect on the three ABC transporters, cell cycle, and apoptosis, in light of the important kinase pathways resulting from the first part of this study. Methods: The PamChip® peptide micro-array profiling was used to determine the level of kinase and targets in the Saudi CRC samples. Next, RT-PCR, MTT cytotoxicity, Western blotting, perturbation of cell cycle, annexin V, and immunofluorescence assays were used to investigate the effect on CRC, MRC5, and HUVEC cells. Results: The kinase activity profiling highlighted the importance of the PI3K/AKT, MAPK, and the growth factors pathways in the Saudi CRC samples. PIK3CA was the most overexpressed, and it was associated with increased level of mutated KRAS and the three ABC transporters, especially ABCC1 in the Saudi samples. Next, combining HAA2020 with 5FU exhibited the best synergistic and resistance-reversal effect in the four CRC cells, and the highest selectivity indices compared to MRC5 and HUVEC normal cells. Additionally, HAA2020 with 5FU exerted significant inhibition of ABCC1 in the four CRC cells, and inhibition of PIK3CA/AKT/MAPK7/ERK in HT29 and HT29-5FU cells. The combination also inhibited EGFR, increased the preG1/S cell cycle phases, apoptosis, and caspase 8 in HT29 cells, while it increased the G1 phase, p21/p27, and apoptosis in HT29-5FU cells. Conclusion: We have combined the PamChip kinase profiling of Saudi CRC samples with in vitro drug combination studies in four CRC cells, highlighting the importance of targeting PIK3CA and ABCC1 for Saudi CRC patients, especially given that the overexpression of PIK3CA mutations was previously linked with the lack of activity for the anti-EGFRs as first line treatment for CRC patients. The combination of HAA2020 and 5FU has selectively sensitized the four CRC cells to 5FU and could be further studied. 相似文献
124.
Imane Es-safi Hamza Mechchate Amal Amaghnouje Omkulthom Mohamed Al Kamaly Fatima Zahra Jawhari Hamada Imtara Andriy Grafov Dalila Bousta 《Molecules (Basel, Switzerland)》2021,26(7)
Depression and anxiety are major mental health problems in all parts of the world. These illnesses are associated with a number of risk factors, including oxidative stress. Psychotropic drugs of a chemical nature have demonstrated several side effects that elevated the impact of those illnesses. Faced with this situation, natural products appear to be a promising alternative. The aim of this study was to evaluate the anxiolytic and antidepressant effects of the Petroselinum sativum polyphenols in vivo, as well as its correlated antioxidant properties in vitro. Anxiolytic activity of the extract (50 and 100 mg/kg) was evaluated using the open field and the light-dark chamber tests, while the antidepressant activity was evaluated using the forced swimming test. The antioxidant activity of the extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical test and the FRAP (iron-reducing capacity) test. The phenolic extract showed very powerful anxiolytic and antidepressant-like effects, especially at a dose of 100 mg/kg, decreasing the depressive behavior in mice (decreased immobility time) and also the anxiolytic behavior (tendency for discovery in the center and illuminated areas) better even than those of paroxetine and bromazepam (classic drugs) concomitant with those results the extract also showed an important antioxidant capacity. These preliminary results suggest that Petroselinum sativum exhibits anxiolytic and antidepressant potential for use as a complement or independent phytomedicine to treat depression and anxiety. 相似文献
125.
Shakeel Ahmad Khan Shafi Ullah Khan Fozia Najeeb Ullah Mohibullah Shah Riaz Ullah Ijaz Ahmad Amal Alotaibi 《Molecules (Basel, Switzerland)》2021,26(7)
Admittedly, the disastrous emergence of drug resistance in prokaryotic and eukaryotic human pathogens has created an urgent need to develop novel chemotherapeutic agents. Onosma chitralicum is a source of traditional medicine with cooling, laxative, and anthelmintic effects. The objective of the current research was to analyze the biological potential of Onosma chitralicum, and to isolate and characterize the chemical constituents of the plant. The crude extracts of the plant prepared with different solvents, such as aqueous, hexane, chloroform, ethyl acetate, and butanol, were subjected to antimicrobial activities. Results corroborate that crude (methanol), EtoAc, and n-C6H14 fractions were more active against bacterial strains. Among these fractions, the EtoAc fraction was found more potent. The EtoAc fraction was the most active against the selected microbes, which was subjected to successive column chromatography, and the resultant compounds 1 to 7 were isolated. Different techniques, such as UV, IR, and NMR, were used to characterize the structures of the isolated compounds 1–7. All the isolated pure compounds (1–7) were tested for their antimicrobial potential. Compounds 1 (4′,8-dimethoxy-7-hydroxyisoflavone), 6 (5,3′,3-trihydroxy-7,4′-dimethoxyflavanone), and 7 (5′,7,8-trihydroxy-6,3′,4′-trimethoxyflavanone) were found to be more active against Staphylococcus aureus and Salmonella Typhi. Compound 1 inhibited S. typhi and S. aureus to 10 ± 0.21 mm and 10 ± 0.45 mm, whereas compound 6 showed inhibition to 10 ± 0.77 mm and 9 ± 0.20 mm, respectively. Compound 7 inhibited S. aureus to 6 ± 0.36 mm. Compounds 6 and 7 showed significant antibacterial potential, and the structure–activity relationship also justifies their binding to the bacterial enzymes, i.e., beta-hydroxyacyl dehydratase (HadAB complex) and tyrosyl-tRNA synthetase. Both bacterial enzymes are potential drug targets. Further, the isolated compounds were found to be active against the tested fungal strains. Whereas docking identified compound 7, the best binder to the lanosterol 14α-demethylase (an essential fungal cell membrane synthesizing enzyme), reported as an antifungal fluconazole binding enzyme. Based on our isolation-linked preliminary structure-activity relationship (SAR) data, we conclude that O. chitralicum can be a good source of natural compounds for drug development against some potential enzyme targets. 相似文献
126.
Moez Guettari Amal Belaidi Stéphane Abel Tahar Tajouri 《Journal of solution chemistry》2017,46(7):1404-1417
The objective of this work is to study the behavior of a neutral polymer, polyvinylpyrrolidone (PVP), in a mixture of water and ethanol. A comparison of the experimental results with a theoretical model of effective solvent interaction with polymer (ESIP) was made. To do so, dynamic light scattering experiments were used to measure the hydrodynamic radius of PVP (M w = 3.6 × 105 g·mol?1) as a function of the ethanol fraction, x A, in the medium at 25 °C. We show that the polymer adopts an ideal chain–globule–coil conformation transition as the ethanol molar fraction varies. This transition is attributed to the change of the solvent quality which results from water and ethanol complex formation. On the other hand, the ternary PVP/water/ethanol system was described by the ESIP model. From the polymer–effective solvent interaction, the second virial coefficient of the polymer/effective solvent and the preferential adsorption parameter were calculated. The obtained results are in agreement with the reported experiments. 相似文献
127.
128.
Amal A. El-Naggar Sahar S. El Sayed Sayeda M. Ibrahim 《Russian Journal of Applied Chemistry》2017,90(2):277-283
Alkaline TiO2 nanoparticles treated cotton/polyester (50/50) blend fabric were prepared, and then exposed to UV irradiation. It was found that the addition of a small amount of TiO2 nanoparticles to the coating solution improves the hydrophilicity and mechanical strength of the fabrics. The treated fabrics exhibited high water absorption as well as better hydrophilicity compared to the untreated sample. Compared to the surface of untreated blend fabric, scanning electron microscopy showed that the surface of the modified blend fabric becomes rough and covered by a layer of other materials. Furthermore, X-ray diffraction demonstrated the formation of crystalline material. In addition, thermograms showed that the modification process improved the thermostability of blend fabric. 相似文献
129.
130.
Awen BZ Unnithan CR Ravi S Kermagy A Sasikumar JM Khrbash AS Ekreem WL 《Natural product research》2011,25(9):927-933
Retama raetam (Forssk) Webb & Berthel is well known in the folk medicine of North and East Mediterranean regions for the treatment of microbial infections. The powdered leaves are used to heal circumcision wounds and used as an antiseptic for wounds, skin rash and pruritus. In this study, to validate this antiseptic property, the chemical composition and antimicrobial activity of the essential oil from the flowers of R. raetam was evaluated. The oil was obtained using hydrodistillation and was analysed by gas chromatography-mass spectrometry. The antibacterial activity was achieved using disc diffusion and broth dilution assay against six bacteria species. Analysis of the essential oil revealed the presence of β-linalool (51%), 2-decen-1-ol (6.6%) and limonene (7.4%) as the major components. The results showed significant activity against microorganisms, especially Staphylococcus aureus, with inhibition zones and minimal inhibitory concentration values in the range of 5.0 mm and 3.0 mg mL?1, respectively. The results on the antibacterial activity provide scientific support for the use of these plants in traditional herbal preparations. 相似文献