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1.
  • Denisova V, Aleksandra, et al. (författare)
  • A Computational Investigation of the Substituent Effects on Geometric, Electronic, and Optical Properties of Siloles and 1,4-Disilacyclohexa-2,5-dienes
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Thirty two differently substituted siloles 1a–1p and 1,4-disilacyclohexa-2,5-dienes 2a–2p were investigated by quantum chemical calculations using the PBE0 hybrid density functional theory (DFT) method. The substituents included σ-electron donating and withdrawing, as well as Ï€-electron donating and withdrawing groups, and their effects when placed at the Si atom(s) or at the C atoms were examined. Focus was placed on geometries, frontier orbital energies and the energies of the first allowed electronic excitations. We analyzed the variation in energies between the orbitals which correspond to HOMO and LUMO for the two parent species, here represented as ΔεHL, motivated by the fact that the first allowed transitions involve excitation between these orbitals. Even though ΔεHL and the excitation energies are lower for siloles than for 1,4-disilacyclohexa-2,5-dienes the latter display significantly larger variations with substitution. The ΔεHL of the siloles vary within 4.57–5.35 eV (ΔΔεHL = 0.78 eV) while for the 1,4-disilacyclohexa-2,5-dienes the range is 5.49–7.15 eV (ΔΔεHL = 1.66 eV). The excitation energy of the first allowed transitions display a moderate variation for siloles (3.60–4.41 eV) whereas the variation for 1,4-disilacyclohexa-2,5-dienes is nearly doubled (4.69–6.21 eV). Cyclobutadisiloles combine the characteristics of siloles and 1,4-disilacyclohexa-2,5-diene by having even lower excitation energies than siloles yet also extensive variation in excitation energies to substitution of 1,4-disilacyclohexa-2,5-dienes (3.47–4.77 eV, variation of 1.30 eV).
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2.
  • Ghalambaz, Mohammad, et al. (författare)
  • Phase-Transition Thermal Charging of a Channel-Shape Thermal Energy Storage Unit : Taguchi Optimization Approach and Copper Foam Inserts
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26
  • Tidskriftsartikel (refereegranskat)abstract
    • Thermal energy storage is a technique that has the potential to contribute to future energy grids to reduce fluctuations in supply from renewable energy sources. The principle of energy storage is to drive an endothermic phase change when excess energy is available and to allow the phase change to reverse and release heat when energy demand exceeds supply. Unwanted charge leakage and low heat transfer rates can limit the effectiveness of the units, but both of these problems can be mitigated by incorporating a metal foam into the design of the storage unit. This study demonstrates the benefits of adding copper foam into a thermal energy storage unit based on capric acid enhanced by copper nanoparticles. The volume fraction of nanoparticles and the location and porosity of the foam were optimized using the Taguchi approach to minimize the charge leakage expected from simulations. Placing the foam layer at the bottom of the unit with the maximum possible height and minimum porosity led to the lowest charge time. The optimum concentration of nanoparticles was found to be 4 vol.%, while the maximu possible concentration was 6 vol.%. The use of an optimized design of the enclosure and the optimum fraction of nanoparticles led to a predicted charging time for the unit that was approximately 58% shorter than that of the worst design. A sensitivity analysis shows that the height of the foam layer and its porosity are the dominant variables, and the location of the porous layer and volume fraction of nanoparticles are of secondary importance. Therefore, a well-designed location and size of a metal foam layer could be used to improve the charging speed of thermal energy storage units significantly. In such designs, the porosity and the placement-location of the foam should be considered more strongly than other factors.
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3.
  • Isroi, Isroi, 1974, et al. (författare)
  • Structural Changes of Oil Palm Empty Fruit Bunch (OPEFB) after Fungal and Phosphoric Acid Pretreatment
  • 2012
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049 .- 1431-5157. ; 17:12, s. 14995-15012
  • Tidskriftsartikel (refereegranskat)abstract
    • Oil palm empty fruit bunch (OPEFB) was pretreated using white-rot fungus Pleurotus floridanus, phosphoric acid or their combination, and the results were evaluated based on the biomass components, and its structural and morphological changes. The carbohydrate losses after fungal, phosphoric acid, and fungal followed by phosphoric acid pretreatments were 7.89%, 35.65%, and 33.77%, respectively. The pretreatments changed the hydrogen bonds of cellulose and linkages between lignin and carbohydrate, which is associated with crystallinity of cellulose of OPEFB. Lateral Order Index (LOI) of OPEFB with no pretreatment, with fungal, phosphoric acid, and fungal followed by phosphoric acid pretreatments were 2.77, 1.42, 0.67, and 0.60, respectively. Phosphoric acid pretreatment showed morphological changes of OPEFB, indicated by the damage of fibre structure into smaller particle size. The fungal-, phosphoric acid-, and fungal followed by phosphoric acid pretreatments have improved the digestibility of OPEFB's cellulose by 4, 6.3, and 7.4 folds, respectively.
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4.
  • Kostag, Marc, et al. (författare)
  • Recent Advances in Solvents for the Dissolution, Shaping and Derivatization of Cellulose : Quaternary Ammonium Electrolytes and their Solutions in Water and Molecular Solvents.
  • 2018
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:3
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a sustained interest in developing solvents for physically dissolving cellulose, i.e., without covalent bond formation. The use of ionic liquids, ILs, has generated much interest because of their structural versatility that results in efficiency as cellulose solvents. Despite some limitations, imidazole-based ILs have received most of the scientific community's attention. The objective of the present review is to show the advantages of using quaternary ammonium electrolytes, QAEs, including salts of super bases, as solvents for cellulose dissolution, shaping, and derivatization, and as a result, increase the interest in further investigation of these important solvents. QAEs share with ILs structural versatility; many are liquids at room temperature or are soluble in water and molecular solvents (MSs), in particular dimethyl sulfoxide. In this review we first give a historical background on the use of QAEs in cellulose chemistry, and then discuss the common, relatively simple strategies for their synthesis. We discuss the mechanism of cellulose dissolution by QAEs, neat or as solutions in MSs and water, with emphasis on the relevance to cellulose dissolution efficiency of the charge and structure of the cation and. We then discuss the use of cellulose solutions in these solvents for its derivatization under homogeneous and heterogeneous conditions. The products of interest are cellulose esters and ethers; our emphasis is on the role of solvent and possible side reactions. The final part is concerned with the use of cellulose dopes in these solvents for its shaping as fibers, a field with potential commercial application.
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5.
  • Stenström, Patrik, et al. (författare)
  • UV-Cured Antibacterial Hydrogels Based on PEG and Monodisperse Heterofunctional Bis-MPA Dendrimers
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:8, s. 2364-
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial infections are one of the major threats to human health due to the raising crisis of antibiotic resistance. Herein, second generation antibacterial heterofunctional dendrimers based on 2,2-bis(methylol)propionic acid were synthesized. The dendrimers possessed six alkenes and 12 ammonium end-groups per molecule and were used to fabricate antibacterial hydrogels together with dithiol-functional polyethylene glycol (mol wt of 2, 6 and 10 kDa) as crosslinkers via thiol-ene chemistry. The network formation can be completed within 10 s upon UV-irradiation as determined by the stabilization of the storage modulus in a rheometer. The hydrogels swelled in aqueous media and could be functionalized with the N-hydroxysuccinimide ester of the dye disperse red 13, which allowed for visually studying the degradation of the hydrogels through the hydrolysis of the ester bonds of the dendritic component. The maximum swelling ratio of the gels was recorded within 4–8 h and the swelling ratios increased with higher molecular weight of the polyethylene glycol crosslinker. The gel formed with 10 kDa polyethylene glycol crosslinker showed the highest swelling ratio of 40 and good mechanical properties, with a storage modulus of 8 kPa. In addition, the hydrogels exhibited good biocompatibility towards both human fibroblasts and mouse monocytes, while showing strong antibacterial activity against both gram-positive and gram-negative bacteria.
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6.
  • Abdissa, Negera, et al. (författare)
  • Cytotoxic Quinones from the roots of Aloe dawei
  • 2014
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 19:3, s. 3264-3273
  • Tidskriftsartikel (refereegranskat)abstract
    • Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC50 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells.
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7.
  • Abouelela, M. E., et al. (författare)
  • Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 26:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease is a global rapidly spreading virus showing very high rates of complications and mortality. Till now, there is no effective specific treatment for the disease. Aloe is a rich source of isolated phytoconstituents that have an enormous range of biological activities. Since there are no available experimental techniques to examine these compounds for antiviral activity against SARS-CoV-2, we employed an in silico approach involving molecular docking, dynamics simulation, and binding free energy calculation using SARS-CoV-2 essential proteins as main protease and spike protein to identify lead compounds from Aloe that may help in novel drug discovery. Results retrieved from docking and molecular dynamics simulation suggested a number of promising inhibitors from Aloe. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) calculations indicated that compounds 132, 134, and 159 were the best scoring compounds against main protease, while compounds 115, 120, and 131 were the best scoring ones against spike glycoprotein. Compounds 120 and 131 were able to achieve significant stability and binding free energies during molecular dynamics simulation. In addition, the highest scoring compounds were investigated for their pharmacokinetic properties and drug-likeness. The Aloe compounds are promising active phytoconstituents for drug development for SARS-CoV-2.
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8.
  • Acevedo Gomez, Yasna, et al. (författare)
  • Performance Recovery after Contamination with Nitrogen Dioxide in a PEM Fuel Cell
  • 2020
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:5
  • Tidskriftsartikel (refereegranskat)abstract
    • While the market for fuel cell vehicles is increasing, these vehicles will still coexist with combustion engine vehicles on the roads and will be exposed to an environment with significant amounts of contaminants that will decrease the durability of the fuel cell. To investigate different recovery methods, in this study, a PEM fuel cell was contaminated with 100 ppm of NO2 at the cathode side. The possibility to recover the cell performance was studied by using different airflow rates, different current densities, and by subjecting the cell to successive polarization curves. The results show that the successive polarization curves are the best choice for recovery; it took 35 min to reach full recovery of cell performance, compared to 4.5 h of recovery with pure air at 0.5 A cm(-2) and 110 mL min(-1). However, the performance recovery at a current density of 0.2 A cm(-2) and air flow 275 mL min(-1) was done in 66 min, which is also a possible alternative. Additionally, two operation techniques were suggested and compared during 7 h of operation: air recovery and air depletion. The air recovery technique was shown to be a better choice than the air depletion technique.
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9.
  • Agback, Peter, et al. (författare)
  • Novel NMR Assignment Strategy Reveals Structural Heterogeneity in Solution of the nsP3 HVD Domain of Venezuelan Equine Encephalitis Virus
  • 2020
  • Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 25
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, intrinsically disordered proteins (IDPs) and disordered domains have attracted great attention. Many of them contain linear motifs that mediate interactions with other factors during formation of multicomponent protein complexes. NMR spectrometry is a valuable tool for characterizing this type of interactions on both amino acid (aa) and atomic levels. Alphaviruses encode a nonstructural protein nsP3, which drives viral replication complex assembly. nsP3 proteins contain over 200-aa-long hypervariable domains (HVDs), which exhibits no homology between different alphavirus species, are predicted to be intrinsically disordered and appear to be critical for alphavirus adaptation to different cells. Previously, we have shown that nsP3 HVD of chikungunya virus (CHIKV) is completely disordered with low tendency to form secondary structures in free form. In this new study, we used novel NMR approaches to assign the spectra for the nsP3 HVD of Venezuelan equine encephalitis virus (VEEV). The HVDs of CHIKV and VEEV have no homology but are both involved in replication complex assembly and function. We have found that VEEV nsP3 HVD is also mostly disordered but contains a short stable alpha-helix in its C-terminal fragment, which mediates interaction with the members of cellular Fragile X syndrome protein family. Our NMR data also suggest that VEEV HVD has several regions with tendency to form secondary structures.
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10.
  • Ahmad, Fawad, et al. (författare)
  • Synthesis of New Naphthyl Aceto Hydrazone-Based Metal Complexes : Micellar Interactions, DNA Binding, Antimicrobial, and Cancer Inhibition Studies
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, naphthyl acetohydrazide (HL) ligand was prepared and used for the synthesis of new six amorphous transition metal (Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II)) complexes. All the compounds were characterized by elemental analysis, UV-vis, FT-IR, 1H- and 13C-NMR, and Matrix-Assisted Laser Desorption Ionization (MALDI). The solubilization study was carried out by estimating the interaction between the metal complexes with surfactants viz. sodium stearate (SS) and Cetyltrimethylammonium bromide (CTAB). UV-Visible spectroscopy was employed to determine partitioning and binding parameters, whereas electrical conductivity measurements were employed to estimate critical micellar concentration (CMC), the extent of dissociation, and free energy of micellization. The CT-DNA interaction of synthesized compounds with DNA represents the major groove binding. The synthesized ligand and metal complexes were also tested against bacterial and fungal strains and it has been observed that Cu(II) complex is active against all the strains except Candida albicans, while Cd(II) complex is active against all bacterial and fungal strains except Pseudomonas. Among all compounds, only the Pd(II) complex shows reasonable activity against cervical cancer HeLa cell lines, representing 97% inhibition.
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11.
  • Al-Hashimi, Osamah, et al. (författare)
  • A Comprehensive Review for Groundwater Contamination and Remediation: Occurrence, Migration and Adsorption Modelling
  • 2021
  • Ingår i: Molecules. - Switzerland : MDPI. - 1431-5157 .- 1420-3049. ; 26:19, s. 5913-5913
  • Tidskriftsartikel (refereegranskat)abstract
    • The provision of safe water for people is a human right; historically, a major number of people depend on groundwater as a source of water for their needs, such as agricultural, industrial or human activities. Water resources have recently been affected by organic and/or inorganic contaminants as a result of population growth and increased anthropogenic activity, soil leaching and pollution. Water resource remediation has become a serious environmental concern, since it has a direct impact on many aspects of people’s lives. For decades, the pump-and-treat method has been considered the predominant treatment process for the remediation of contaminated groundwater with organic and inorganic contaminants. On the other side, this technique missed sustainability and the new concept of using renewable energy. Permeable reactive barriers (PRBs) have been implemented as an alternative to conventional pump-and-treat systems for remediating polluted groundwater because of their effectiveness and ease of implementation. In this paper, a review of the importance of groundwater, contamination and biological, physical as well as chemical remediation techniques have been discussed. In this review, the principles of the permeable reactive barrier’s use as a remediation technique have been introduced along with commonly used reactive materials and the recent applications of the permeable reactive barrier in the remediation of different contaminants, such as heavy metals, chlorinated solvents and pesticides. This paper also discusses the characteristics of reactive media and contaminants’ uptake mechanisms. Finally, remediation isotherms, the breakthrough curves and kinetic sorption models are also being presented. It has been found that groundwater could be contaminated by different pollutants and must be remediated to fit human, agricultural and industrial needs. The PRB technique is an efficient treatment process that is an inexpensive alternative for the pump-and-treat procedure and represents a promising technique to treat groundwater pollution. 
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12.
  • Al-Rudainy, Basel, et al. (författare)
  • Hemicellulose Recovery from Spent-Sulfite-Liquor: Lignin Removal by Adsorption to Resins for Improvement of the Ultrafiltration Process
  • 2020
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 25:15
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, three polymeric resins were examined as alternatives for the separation of hemicellulose and lignin. The aim was to remove the lignin from spent-sulfite-liquor (SSL) prior to ultrafiltration, producing a hemicellulose-rich retentate with high purity, and increase the capacity of the membrane filtration. The lignin in the SSL was sulfonated; thus, two of the resins were anion exchangers and 1 was hydrophobic. The data from the equilibrium studies and adsorption kinetics were fitted to established models, and the results were interpreted based on these observations. The strongly basic anion exchanger performed best with regard to lignin removal. The adsorption followed the Sips isotherm, indicating that the process was cooperative with chemisorption as the main reaction between the adsorbate and adsorbent based on the kinetics. Regeneration of the adsorbent was also possible, wherein 100 g/L NaCl was sufficient to recover 98% of the lignin. The lignin removal had a positive effect on the ultrafiltration process, in which the flux increased by 38% and the extent of separation between the hemicellulose and lignin rose from 17% to 59%.
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13.
  • Alajlani, Muaaz Mutaz, et al. (författare)
  • Evaluating Antimycobacterial Screening Schemes Using Chemical Global Positioning System-Natural Product Analysis
  • 2020
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Most of the targeted discoveries in tuberculosis research have covered previously explored chemical structures but neglected physiochemical properties. Until now, no efficient prediction tools have been developed to discriminate the novelty of screened compounds at early stages. To overcome this deficit, a drastic novel approach must include physicochemical properties filters provided by Chemical Global Positioning System-Natural Product analysis (ChemGPS-NP). Three different screening schemes GSK, GVKBio, and NIAID provided 776, 2880, and 3779 compounds respectively and were evaluated based on their physicochemical properties and thereby proposed as deduction examples. Charting the physiochemical property spaces of these sets identified the merits and demerits of each screening scheme by simply observing the distribution over the chemical property space. We found that GSK screening set was confined to a certain space, losing potentially active compounds when compared with an in-house constructed 459 highly active compounds (active set), while the GVKBio and NIAID screening schemes were evenly distributed through space. The latter two sets had the advantage, as they have covered a larger space and presented compounds with additional variety of properties and activities. The in-house active set was cross-validated with MycPermCheck and SmartsFilter to be able to identify priority compounds. The model demonstrated undiscovered spaces when matched with Maybridge drug-like space, providing further potential targets. These undiscovered spaces should be considered in any future investigations. We have included the most active compounds along with permeability and toxicity filters as supplemented material.
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14.
  • Alajlani, Muaaz Mutaz (författare)
  • The Chemical Property Position of Bedaquiline Construed by a Chemical Global Positioning System-Natural Product
  • 2022
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 27:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Bedaquiline is a novel adenosine triphosphate synthase inhibitor anti-tuberculosis drug. Bedaquiline belongs to the class of diarylquinolines, which are antituberculosis drugs that are quite different mechanistically from quinolines and flouroquinolines. The fact that relatively similar chemical drugs produce different mechanisms of action is still not widely understood. To enhance discrimination in favor of bedaquiline, a new approach using eight-score principal component analysis (PCA), provided by a ChemGPS-NP model, is proposed. PCA scores were calculated based on 35 + 1 different physicochemical properties and demonstrated clear differences when compared with other quinolines. The ChemGPS-NP model provided an exceptional 100 compounds nearest to bedaquiline from antituberculosis screening sets (with a cumulative Euclidian distance of 196.83), compared with the different 2Dsimilarity provided by Tanimoto methods (extended connective fingerprints and the Molecular ACCess System, showing 30% and 182% increases in cumulative Euclidian distance, respectively). Potentially similar compounds from publicly available antituberculosis compounds and Maybridge sets, based on bedaquiline's eight-dimensional similarity and different filtrations, were identified too.
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15.
  • Ali, Sara E., et al. (författare)
  • Profiling Metabolites and Biological Activities of Sugarcane (Saccharum officinarum Linn.) Juice and Its Product Molasses via a Multiplex Metabolomics Approach
  • 2019
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Sugarcane (Saccharum officinarum L.) is an important perennial grass in the Poaceae family cultivated worldwide due to its economical and medicinal value. In this study, a combined approach using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy was employed for the large-scale metabolite profiling of sugarcane juice and its by-product molasses. The polyphenols were analysed via UPLC-UV-ESI-MS, whereas the primary metabolites such as sugars and organic and amino acids were profiled using NMR spectroscopy and gas chromatography/mass spectrometry (GC/MS). UPLC/MS was more effective than NMR spectroscopy or GC/MS for determining differences among the metabolite compositions of the products. Under the optimized conditions, UPLC/MS led to the identification of 42 metabolites, including nine flavonoids, nine fatty acids, and two sterols. C/O Flavone glycosides were the main subclass detected, with tricin-7-O-deoxyhexosyl glucuronide being detected in sugarcane and molasses for the first time. Based on GC/MS analysis, disaccharides were the predominant species in the sugarcane juice and molasses, with sucrose accounting for 66% and 59%, respectively, by mass of all identified metabolites. The phenolic profiles of sugarcane and molasses were further investigated in relation to their in vitro antioxidant activities using free radical scavenging assays such as 2,2-Diphenyl-1-picrylhydrazyl free radical-scavenging ability (DPPH), Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). In view of its higher total phenolic content (TPC) (196 +/- 2.1 mg GAE/100 g extract) compared to that of sugarcane juice (93 +/- 2.9 mg GAE/100 g extract), molasses exhibited a substantially higher antioxidant effect. Interestingly, both extracts were also found to inhibit alpha-glucosidase and alpha-amylase enzymes, suggesting a possible antihyperglycaemic effect. These findings suggest molasses may be a new source of natural antioxidants for functional foods.
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16.
  • Allgardsson, Anders, et al. (författare)
  • An unusual dimeric inhibitor of acetylcholinesterase : cooperative binding of crystal violet
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself.
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17.
  • Amarouch, Mohamed-Yassine, et al. (författare)
  • Biophysical Characterization of Epigallocatechin-3-Gallate Effect on the Cardiac Sodium Channel Na(v)1.5
  • 2020
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigallocatechin-3-Gallate (EGCG) has been extensively studied for its protective effect against cardiovascular disorders. This effect has been attributed to its action on multiple molecular pathways and transmembrane proteins, including the cardiac Na(v)1.5 channels, which are inhibited in a dose-dependent manner. However, the molecular mechanism underlying this effect remains to be unveiled. To this aim, we have characterized the EGCG effect on Na(v)1.5 using electrophysiology and molecular dynamics (MD) simulations. EGCG superfusion induced a dose-dependent inhibition of Na(v)1.5 expressed in tsA201 cells, negatively shifted the steady-state inactivation curve, slowed the inactivation kinetics, and delayed the recovery from fast inactivation. However, EGCG had no effect on the voltage-dependence of activation and showed little use-dependent block on Na(v)1.5. Finally, MD simulations suggested that EGCG does not preferentially stay in the center of the bilayer, but that it spontaneously relocates to the membrane headgroup region. Moreover, no sign of spontaneous crossing from one leaflet to the other was observed, indicating a relatively large free energy barrier associated with EGCG transport across the membrane. These results indicate that EGCG may exert its biophysical effect via access to its binding site through the cell membrane or via a bilayer-mediated mechanism.
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18.
  • Andersson, Pierre, et al. (författare)
  • B-norsteroids from Hymenoscyphus pseudoalbidus
  • 2012
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 17, s. 7769-7781
  • Tidskriftsartikel (refereegranskat)abstract
    • Two viridin-related B-norsteroids, B-norviridiol lactone (1) and B-norviridin enol (2), both possessing distinct unprecedented carbon skeletons, were isolated from a liquid culture of the ash dieback-causing fungus Hymenoscyphus pseudoalbidus. Compound 2 was found to degrade to a third B-norsteroidal compound, 1β-hydroxy-2α-hydro-asterogynin A (3), which was later detected in the original culture. The proposed structure of 1 is, regarding connectivity, identical to the original erroneous structure for TAEMC161, which was later reassigned as viridiol. Compound 2 showed an unprecedented 1H-13C HMBC correlation through an intramolecular hydrogen bond. The five-membered B-ring of compounds 1–3 was proposed to be formed by a benzilic acid rearrangement. The known compound asterogynin A was found to be formed from 3 by a β-elimination of water. All compounds were characterized by NMR spectroscopy, LC-HRMS and polarimetry.
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19.
  • Asa'ad, Farah, 1983, et al. (författare)
  • The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration-A Review.
  • 2020
  • Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 25:24
  • Tidskriftsartikel (refereegranskat)abstract
    • The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better tissue regeneration? Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.
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20.
  • Atilaw, Y., et al. (författare)
  • Four Prenylflavone Derivatives with Antiplasmodial Activities from the Stem of Tephrosia purpurea subsp leptostachya
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 22:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Four new flavones with modified prenyl groups, namely (E)-5-hydroxytephrostachin (1), purleptone (2), (E)-5-hydroxyanhydrotephrostachin (3), and terpurlepflavone (4), along with seven known compounds (5-11), were isolated from the CH2Cl2/MeOH (1:1) extract of the stem of Tephrosia purpurea subsp. leptostachya, a widely used medicinal plant. Their structures were elucidated on the basis of NMR spectroscopic and mass spectrometric evidence. Some of the isolated compounds showed antiplasmodial activity against the chloroquine-sensitive D6 strains of Plasmodium falciparum, with (E)-5-hydroxytephrostachin (1) being the most active, IC50 1.7 +/- 0.1 mu M, with relatively low cytotoxicity, IC50 > 21 mu M, against four cell-lines.
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21.
  • Atilaw, Y., et al. (författare)
  • Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 22:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In our search for new antiplasmodial agents, the CH2Cl2/CH3OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2,6-dimethoxy-3,4-(2,2-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4-ethoxy-3-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.
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22.
  • Awadalla, M. K. A., et al. (författare)
  • Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1
  • 2016
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1431-5157. ; 21:3
  • Tidskriftsartikel (refereegranskat)abstract
    • A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were assessed by docking of the natural substrate all-trans-retinoic acid (atRA), and a group of known azole- and tetralone-based CYP26A1 inhibitors. The preferred binding pose of atRA suggests the (4S)-OH-atRA metabolite production, in agreement with recently available experimental data. The distances between the ligands and the heme group iron of the enzyme are in agreement with corresponding distances obtained for substrates and azole inhibitors for other cytochrome systems. The calculated theoretical binding energies agree with recently reported experimental data and show that the model is capable of discriminating between natural substrate, strong inhibitors (R116010 and R115866), and weak inhibitors (liarozole, fluconazole, tetralone derivatives).
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23.
  • Baghaei, Behnaz, 1986-, et al. (författare)
  • All-Cellulose Composites: A Review of RecentStudies on Structure, Properties and Applications
  • 2020
  • Ingår i: Molecules. - Borås : MDPI AG. - 1431-5157 .- 1420-3049. ; 25:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Nowadays, there is greater demand for greener materials in societies due to environmental consciousness, depleting fossil fuels and growing ecological concerns. Within the foreseeable future, industries and suppliers will be required to be more aware of challenges faced due to the availability of resources and use more sustainable and renewable raw materials. In this context, cellulose can be expected to become a vital resource for materials owing to its abundance, versatility as a biopolymer, several different forms and potential applications. Thus, all-cellulose composites (ACCs) have gained significant research interest in recent years. ACC is a class of biocomposites in which the matrix is a dissolved and regenerated cellulose, while the reinforcement is undissolved or partly dissolved cellulose. This review paper is intended to provide a brief outline of works that cover recent progress in the manufacturing and processing techniques for ACCs, various cellulose sources, solvents and antisolvents, as well as their properties.
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24.
  • Bagon, BB, et al. (författare)
  • Exploring the Bile Stress Response of Lactobacillus mucosae LM1 through Exoproteome Analysis
  • 2021
  • Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 26:18
  • Tidskriftsartikel (refereegranskat)abstract
    • Lactobacillus sp. have long been studied for their great potential in probiotic applications. Recently, proteomics analysis has become a useful tool for studies on potential lactobacilli probiotics. Specifically, proteomics has helped determine and describe the physiological changes that lactic acid bacteria undergo in specific conditions, especially in the host gut. In particular, the extracellular proteome, or exoproteome, of lactobacilli contains proteins specific to host– or environment–microbe interactions. Using gel-free, label-free ultra-high performance liquid chromatography tandem mass spectrometry, we explored the exoproteome of the probiotic candidate Lactobacillus mucosae LM1 subjected to bile treatment, to determine the proteins it may use against bile stress in the gut. Bile stress increased the size of the LM1 exoproteome, secreting ribosomal proteins (50S ribosomal protein L27 and L16) and metabolic proteins (lactate dehydrogenase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate dehydrogenases, among others) that might have moonlighting functions in the LM1 bile stress response. Interestingly, membrane-associated proteins (transporters, peptidase, ligase and cell division protein ftsH) were among the key proteins whose secretion were induced by the LM1 bile stress response. These specific proteins from LM1 exoproteome will be useful in observing the proposed bile response mechanisms via in vitro experiments. Our data also reveal the possible beneficial effects of LM1 to the host gut.
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25.
  • Baldassarre, Maurizio, et al. (författare)
  • Simultaneous Fitting of Absorption Spectra and Their Second Derivatives for an Improved Analysis of Protein Infrared Spectra
  • 2015
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 20:7, s. 12599-12622
  • Tidskriftsartikel (refereegranskat)abstract
    • Infrared spectroscopy is a powerful tool in protein science due to its sensitivity to changes in secondary structure or conformation. In order to take advantage of the full power of infrared spectroscopy in structural studies of proteins, complex band contours, such as the amide I band, have to be decomposed into their main component bands, a process referred to as curve fitting. In this paper, we report on an improved curve fitting approach in which absorption spectra and second derivative spectra are fitted simultaneously. Our approach, which we name co-fitting, leads to a more reliable modelling of the experimental data because it uses more spectral information than the standard approach of fitting only the absorption spectrum. It also avoids that the fitting routine becomes trapped in local minima. We have tested the proposed approach using infrared absorption spectra of three mixed α/β proteins with different degrees of spectral overlap in the amide I region: ribonuclease A, pyruvate kinase, and aconitase.
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26.
  • Ban, Zeljka, et al. (författare)
  • Flexibility and Preorganization of Fluorescent Nucleobase-Pyrene Conjugates Control DNA and RNA Recognition
  • 2020
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 25:9
  • Tidskriftsartikel (refereegranskat)abstract
    • We synthesized a new amino acid-fluorescent nucleobase derivative (qAN1-AA) and from it two new fluorescent nucleobase-fluorophore (pyrene) conjugates, whereby only the analogue with the longer and more flexible linker (qAN1-pyr2) self-folded into intramolecularly stacked qAN1/pyrene conformation, yielding characteristic, 100 nm-red-shifted emission (lambda(max) = 500 nm). On the contrary, the shorter and more rigid linker resulted in non-stacked conformation (qAN1-pyr1), characterized by the emission of free pyrene at lambda(max) = 400 nm. Both fluorescent nucleobase-fluorophore (pyrene) conjugates strongly interacted with ds-DNA/RNA grooves with similar affinity but opposite fluorescence response (due to pre-organization), whereas the amino acid-fluorescent base derivative (qAN1-AA) was inactive. However, only intramolecularly self-folded qAN1-pyr2 showed strong fluorescence selectivity toward poly U (Watson-Crick complementary to qAN1 nucleobase) and poly A (reverse Hoogsteen complementary to qAN1 nucleobase), while an opposite emission change was observed for non-complementary poly G and poly C. Non-folded analogue (qAN1-pyr1) showed no ss-RNA selectivity, demonstrating the importance of nucleobase-fluorophore pre-organization.
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27.
  • Baran, Tomasz, et al. (författare)
  • Copper oxide-based photocatalysts and photocathodes: Fundamentals and recent advances
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049 .- 1431-5157. ; 26:23
  • Forskningsöversikt (refereegranskat)abstract
    • This work aims at reviewing the most impactful results obtained on the development of Cu-based photocathodes. The need of a sustainable exploitation of renewable energy sources and the parallel request of reducing pollutant emissions in airborne streams and in waters call for new technologies based on the use of efficient, abundant, low-toxicity and low-cost materials. Photoelectrochemical devices that adopts abundant element-based photoelectrodes might respond to these requests being an enabling technology for the direct use of sunlight to the production of energy fuels form water electrolysis (H2) and CO2 reduction (to alcohols, light hydrocarbons), as well as for the degradation of pollutants. This review analyses the physical chemical properties of Cu2O (and CuO) and the possible strategies to tune them (doping, lattice strain). Combining Cu with other elements in multinary oxides or in composite photoelectrodes is also discussed in detail. Finally, a short overview on the possible applications of these materials is presented.
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28.
  • Barzegar, Hamid Reza, et al. (författare)
  • Water assisted growth of C60 rods and tubes by liquid-liquid interfacial precipitation method
  • 2012
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 17:6, s. 6840-6853
  • Tidskriftsartikel (refereegranskat)abstract
    • C60 nanorods with hexagonal cross sections are grown using a static liquid-liquid interfacial precipitation method in a system of C60/m-dichlorobenzene solution and ethanol. Adding water to the ethanol phase leads instead to C60 tubes where both length and diameter of the C60 tubes can be controlled by the water content in the ethanol. Based on our observations we find that the diameter of the rods/tubes strongly depends on the nucleation step. We propose a liquid-liquid interface growth model of C60 rods and tubes based on the diffusion rate of the good C60 containing solvent into the poor solvent as well as on the size of the crystal seeds formed at the interface between the two solvents. The grown rods and tubes exhibit a hexagonal solvate crystal structure with m-dichlorobenzene solvent molecules incorporated into the crystal structure, independent of the water content. An annealing step at 200 °C at a pressure <1 kPa transforms the grown structures into a solvent-free face centered cubic structure. Both the hexagonal and the face centered cubic structures are very stable and neither morphology nor structure shows any signs of degradation after three months of storage.
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29.
  • Bassyouni, Fatma, et al. (författare)
  • Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives : Molecular Modeling and Biological Evaluation with Histopathological Effect
  • 2021
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes is the most common metabolic disorder in both developing and non-developing countries, and a well-recognized global health problem. The WHO anticipates an increase in cases from 171 million in 2000 to 366 million by 2030. In the present study, we focus on the preparation of pyrimidine derivatives as potential antidiabetic and antimicrobial agents. Thein vivoeffect on total serum glucose concentration, cholesterol and antioxidant activity was assessed in adult male albino Wister rats and compared to the reference drug glimperide. Promising results were observed for compound 5. The histopathological study confirms that compound 5 results in significant activity with liver maintenance. The antimicrobial activities were evaluated against several bacterial strains such as Salmonella typhimurium ATCC 25566, Bacillus cereus, Escherichia coli NRRN 3008, Pseudomonas aeruginosa ATCC 10145, Staphylococcus aureus ATCC 6538and fungi such as Rhizopus oligosporus, Mucor miehei and Asperillus niger. Compounds 4 and 5 showed a good inhibition of the bacterial zone compared to the reference drug cephradine. Finally, we suggest protein targets for these drugs based on computational analysis, and infer their activities from their predicted modes of binding using molecular modeling. The molecular modeling for compounds 4 and 5 resulted in improved docking scores and hydrogen bonding. The docking studies are in good agreement with the in vitro and in vivo studies.
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30.
  • Baun, Christina, et al. (författare)
  • Preclinical Evaluation of the Copper-64 Labeled GRPR-Antagonist RM26 in Comparison with the Cobalt-55 Labeled Counterpart for PET-Imaging of Prostate Cancer
  • 2020
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 25:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Gastrin-releasing peptide receptor (GRPR) is overexpressed in the majority of prostate cancers. This study aimed to investigate the potential of 64Cu (radionuclide for late time-point PET-imaging) for imaging of GRPR expression using NOTA-PEG2-RM26 and NODAGA-PEG2-RM26. Methods: NOTA/NODAGA-PEG2-RM26 were labeled with 64Cu and evaluated in GRPR-expressing PC-3 cells. Biodistribution of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was studied in PC-3 xenografted mice and compared to the biodistribution of [57Co]Co-NOTA/NODAGA-PEG2-RM26 at 3 and 24 h p.i. Preclinical PET/CT imaging was performed in tumor-bearing mice. NOTA/NODAGA-PEG2-RM26 were stably labeled with 64Cu with quantitative yields. In vitro, binding of [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was rapid and GRPR-specific with slow internalization. In vivo, [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 bound specifically to GRPR-expressing tumors with fast clearance from blood and normal organs and displayed generally comparable biodistribution profiles to [57Co]Co-NOTA/NODAGA-PEG2-RM26; tumor uptake exceeded normal tissue uptake 3 h p.i.. Tumor-to-organ ratios did not increase significantly with time. [64Cu]Cu-NOTA-PEG2-RM26 had a significantly higher liver and pancreas uptake compared to other agents. 57Co-labeled radioconjugates showed overall higher tumor-to-non-tumor ratios, compared to the 64Cu-labeled counterparts. [64Cu]Cu-NOTA/NODAGA-PEG2-RM26 was able to visualize GRPR-expression in a murine PC model using PET. However, [55/57Co]Co-NOTA/NODAGA-PEG2-RM26 provided better in vivo stability and overall higher tumor-to-non-tumor ratios compared with the 64Cu-labeled conjugates.
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31.
  • Bednarska, Joanna, et al. (författare)
  • Nonempirical Simulations of Inhomogeneous Broadening of Electronic Transitions in Solution : Predicting Band Shapes in One- and Two-Photon Absorption Spectra of Chalcones
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We have examined several approaches relying on the Polarizable Embedding (PE) scheme to predict optical band shapes for two chalcone molecules in methanol solution. The PE-TDDFT and PERI-CC2 methods were combined with molecular dynamics simulations, where the solute geometry was kept either as rigid, flexible or partly-flexible (restrained) body. The first approach, termed RBMD-PE-TDDFT, was employed to estimate the inhomogeneous broadening for subsequent convolution with the vibrationally-resolved spectra of the molecule in solution determined quantum-mechanically (QM). As demonstrated, the RBMD-PE-TDDFT/QM-PCM approach delivers accurate band widths, also reproducing their correct asymmetric shapes. Further refinement can be obtained by the estimation of the inhomogeneous broadening using the RBMD-PERI-CC2 method. On the other hand, the remaining two approaches (FBMD-PE-TDDFT and ResBMD-PE-TDDFT), which lack quantum-mechanical treatment of molecular vibrations, lead to underestimated band widths. In this study, we also proposed a simple strategy regarding the rapid selection of the exchange-correlation functional for the simulations of vibrationally-resolved one-and two-photon absorption spectra based on two easy-to-compute metrics.
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32.
  • Behren, Sandra, et al. (författare)
  • Glycopeptides and -Mimetics to Detect, Monitor and Inhibit Bacterial and Viral Infections : Recent Advances and Perspectives
  • 2019
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:6
  • Forskningsöversikt (refereegranskat)abstract
    • The initial contact of pathogens with host cells is usually mediated by their adhesion to glycan structures present on the cell surface in order to enable infection. Furthermore, glycans play important roles in the modulation of the host immune responses to infection. Understanding the carbohydrate-pathogen interactions are of importance for the development of novel and efficient strategies to either prevent, or interfere with pathogenic infection. Synthetic glycopeptides and mimetics thereof are capable of imitating the multivalent display of carbohydrates at the cell surface, which have become an important objective of research over the last decade. Glycopeptide based constructs may function as vaccines or anti-adhesive agents that interfere with the ability of pathogens to adhere to the host cell glycans and thus possess the potential to improve or replace treatments that suffer from resistance. Additionally, synthetic glycopeptides are used as tools for epitope mapping of antibodies directed against structures present on various pathogens and have become important to improve serodiagnostic methods and to develop novel epitope-based vaccines. This review will provide an overview of the most recent advances in the synthesis and application of glycopeptides and glycopeptide mimetics exhibiting a peptide-like backbone in glycobiology.
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33.
  • Benchoula, Khaled, et al. (författare)
  • Optimization of Hyperglycemic Induction in Zebrafish and Evaluation of Its Blood Glucose Level and Metabolite Fingerprint Treated with Psychotria malayana Jack Leaf Extract
  • 2019
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:8
  • Tidskriftsartikel (refereegranskat)abstract
    • A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.
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34.
  • Bergman, Sara, et al. (författare)
  • Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [C-11] carbon monoxide. Starting with amines and [C-11] carbon monoxide, both symmetrical and unsymmetrical C-11-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [C-11] carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/mu mol-319 GBq/mu mol). DFT calculations were found to support a reaction mechanism proceeding through an C-11-labelled isocyanate intermediate.
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35.
  • Berktas, Ilayda, et al. (författare)
  • Facile synthesis of graphene from waste tire/silica hybrid additives and optimization study for the fabrication of thermally enhanced cement grouts
  • 2020
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 25:4
  • Tidskriftsartikel (refereegranskat)abstract
    • This work evaluates the effects of newly designed graphene/silica hybrid additives on the properties of cementitious grout. In the hybrid structure, graphene nanoplatelet (GNP) obtained from waste tire was used to improve the thermal conductivity and reduce the cost and environmental impacts by using recyclable sources. Additionally, functionalized silica nanoparticles were utilized to enhance the dispersion and solubility of carbon material and thus the hydrolyzable groups of silane coupling agent were attached to the silica surface. Then, the hybridization of GNP and functionalized silica was conducted to make proper bridges and develop hybrid structures by tailoring carbon/silica ratios. Afterwards, special grout formulations were studied by incorporating these hybrid additives at different loadings. As the amount of hybrid additive incorporated into grout suspension increased from 3 to 5 wt%, water uptake increased from 660 to 725 g resulting in the reduction of thermal conductivity by 20.6%. On the other hand, as the concentration of GNP in hybrid structure increased, water demand was reduced, and thus the enhancement in thermal conductivity was improved by approximately 29% at the same loading ratios of hybrids in the prepared grout mixes. Therefore, these developed hybrid additives showed noticeable potential as a thermal enhancement material in cement-based grouts. © 2020 by the authors.
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36.
  • Björklund, Erland, et al. (författare)
  • Total Release of 21 Indicator Pharmaceuticals Listed by the Swedish Medical Products Agency from Wastewater Treatment Plants to Surface Water Bodies in the 1.3 Million Populated County Skane (Scania), Sweden
  • 2021
  • Ingår i: Molecules. - : MDPI Multidisciplinary Digital Publishing Institute. - 1420-3049. ; 27:1, s. 1-28
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2017, the Swedish Environmental Protection Agency published a report on advanced wastewater treatment for the removal of pharmaceutical residues and stated that advanced treatment should be implemented where it will make the largest difference from an environmental perspective. However, the report also concluded that this need cannot be specified with existing data, but consideration must be made of local conditions. Two considerations are (1) the discharged amount of pharmaceutical into receiving water bodies and (2) the turnover of water in the recipient, where the highest risks are related to recipients with a low water turnover and low dilution. The current project comprised eight different WWTPs distributed throughout the entire County Skåne (Scania) in Sweden, with a population of ca. 1,300,000 persons. In total, 21 of 22 pharmaceuticals were analyzed according to the list proposed by the Swedish Medical Products Agency 2015. The results show that large amounts of pharmaceuticals are released from the WWTPs yearly to Scanian recipients. The total discharge of pharmaceuticals from the eight treatment plants adds up to 71 kg of these 21 substances alone, mainly comprising metoprolol, which is a drug that lowers blood pressure, and the analgesic drug diclofenac. Additionally, carbamazepine, losartan, naproxen and oxazepam were present in significant concentrations. These represented three illnesses that are very common: high blood pressure, inflammation/pain and depression/anxiety. The concentrations were generally in line with previous national Swedish screenings. It was estimated that, when one million cubic meters (1,000,000 m3 ) of wastewater is discharged, almost 4 kg of the 21 pharmaceuticals is released. The total volume wastewater release by the >90 WWTPs in Scania was estimated to 152,887,000 m3, which corresponded to 590 kg/year. The investigated 21 drugs cover only a small part of many hundred pharmaceuticals that are in use in Sweden. Thus, most likely, one or several tons of pharmaceuticals leak out to the Scanian recipients annually. The analysis of river samples shows that the dilution of wastewater is a key parameter in reducing concentrations. However, some locations have remarkably high concentrations, which occur when the volume wastewater is large in relation to the flow in the river. These kinds of regional results are of importance when selecting where advanced treatment should be prioritized in a first instance, as requested by the Swedish EPA.
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37.
  • Blom, Magnus, 1984-, et al. (författare)
  • Synthesis and Properties of Bis-Porphyrin Molecular Tweezers : Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis
  • 2016
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to  the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle  differences between these tweezers, that are discussed in terms of porphyrin dislocation  modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen  guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.
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38.
  • Borroto-Escuela, Dasiel O., et al. (författare)
  • Receptor-Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment
  • 2018
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:6
  • Forskningsöversikt (refereegranskat)abstract
    • Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A-FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A-5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1-15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1-GalR2-5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.
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39.
  • Broberg, Anders, et al. (författare)
  • Labradorins with antibacterial activity produced by Pseudomonas sp.
  • 2017
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 22
  • Tidskriftsartikel (refereegranskat)abstract
    • The urgent need for new antibacterial drugs has led to renewed interest in microorganisms, which historically have been the main source of previously discovered antibiotics. The present study describes the discovery of two new antibacterial oxazolylindole type alkaloids, labradorins 5 (1) and 6 (2), which were isolated and characterized from two isolates of Pseudomonas sp., along with four previously known tryptophane derived alkaloids. The structures of 1 and 2 were determined by NMR spectroscopy and MS, and confirmed by synthesis. During bioassay-guided isolation using several human bacterial pathogens, 1 and 2 displayed activity towards Staphylococcus aureus and Acinetobacter baumannii. The minimal inhibitory concentrations (MIC) of compounds 1 and 2 against S. aureus were 12 mu g.mL(-1) and 50 mu g.mL(-1), respectively, whereas the MICs against A. baumannii were > 50 mu g.mL(-1). The CC50 values of compound 1 towards a liver cell line (HEP-G2) and a T-cell line (MT4) were 30 mu g.mL(-1) and 20 mu g.mL(-1), respectively, and for compound 2 were > 100 mu g.mL(-1) and 20 mu g.mL(-1), respectively. Due to the limited potency of compounds 1 and 2, along with their toxicity, the compounds do not warrant further development towards new antibiotics.
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40.
  • Burkina, Viktoriia, et al. (författare)
  • In Vitro Metabolic Transformation of Pharmaceuticals by Hepatic S9 Fractions from Common Carp (Cyprinus carpio)
  • 2020
  • Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 25
  • Tidskriftsartikel (refereegranskat)abstract
    • Water from wastewater treatment plants contains concentrations of pharmaceutically active compounds as high as micrograms per liter, which can adversely affect fish health and behavior, and contaminate the food chain. Here, we tested the ability of the common carp hepatic S9 fraction to produce the main metabolites from citalopram, metoprolol, sertraline, and venlafaxine. Metabolism in fish S9 fractions was compared to that in sheep. The metabolism of citalopram was further studied in fish. Our results suggest a large difference in the rate of metabolites formation between fish and sheep. Fish hepatic S9 fractions do not show an ability to form metabolites from venlafaxine, which was also the case for sheep. Citalopram, metoprolol, and sertraline were metabolized by both fish and sheep S9. Citalopram showed concentration-dependent N-desmethylcitalopram formation with V-max = 1781 pmol/min/mg and K-m = 29.7 mu M. The presence of ellipticine, a specific CYP1A inhibitor, in the incubations reduced the formation of N-desmethylcitalopram by 30-100% depending on the applied concentration. These findings suggest that CYP1A is the major enzyme contributing to the formation of N-desmethylcitalopram. In summary, the results from the present in vitro study suggest that common carp can form the major metabolites of citalopram, metoprolol, and sertraline.
  •  
41.
  • Cabaleiro-Lago, Celia, et al. (författare)
  • The effect of nanoparticles on the structure and enzymatic activity of human carbonic anhydrase I and II
  • 2020
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 25:19
  • Forskningsöversikt (refereegranskat)abstract
    • Human carbonic anhydrases (hCAs) belong to a well characterized group of metalloenzymes that catalyze the conversion of carbonic dioxide into bicarbonate. There are currently 15 known human isoforms of carbonic anhydrase with different functions and distribution in the body. This links to the relevance of hCA variants to several diseases such as glaucoma, epilepsy, mountain sickness, ulcers, osteoporosis, obesity and cancer. This review will focus on two of the human isoforms, hCA I and hCA II. Both are cytosolic enzymes with similar topology and 60% sequence homology but different catalytic efficiency and stability. Proteins in general adsorb on surfaces and this is also the case for hCA I and hCA II. The adsorption process can lead to alteration of the original function of the protein. However, if the function is preserved interesting biotechnological applications can be developed. This review will cover the knowledge about the interaction between hCAs and nanomaterials. We will highlight how the interaction may lead to conformational changes that render the enzyme inactive. Moreover, the importance of different factors on the final effect on hCAs, such as protein stability, protein hydrophobic or charged patches and chemistry of the nanoparticle surface will be discussed.
  •  
42.
  • Ceresino, Elaine Berger, et al. (författare)
  • Lupin Protein Isolate Structure Diversity in Frozen-Cast Foams : Effects of Transglutaminases and Edible Fats
  • 2021
  • Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 26:6
  • Tidskriftsartikel (refereegranskat)abstract
    • This study addresses an innovative approach to generate aerated foods with appealing texture through the utilization of lupin protein isolate (LPI) in combination with edible fats. We show the impact of transglutaminases (TGs; SB6 and commercial), glycerol (Gly), soy lecithin (Lec) and linoleic acid (LA) on the micro- and nanostructure of health promoting solid foods created from LPI and fats blends. 3-D tomographic images of LPI with TG revealed that SB6 contributed to an exceptional bubble spatial organization. The inclusion of Gly and Lec decreased protein polymerization and also induced the formation of a porous layered material. LA promoted protein polymerization and formation of homogeneous thick layers in the LPI matrix. Thus, the LPI is a promising protein resource which when in blend with additives is able to create diverse food structures. Much focus has been placed on the great foamability of LPI and here we show the resulting microstructure of LPI foams, and how these were improved with addition of TGs. New food applications for LPI can arise with the addition of food grade dispersant Lec and essential fatty-acid LA, by improved puffiness, and their contributing as replacer of chemical leavening additives in gluten-free products.
  •  
43.
  • Chen, Yujie, et al. (författare)
  • Shape-Memory Polymeric Artificial Muscles : Mechanisms, Applications and Challenges
  • 2020
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:18
  • Forskningsöversikt (refereegranskat)abstract
    • Shape-memory materials are smart materials that can remember an original shape and return to their unique state from a deformed secondary shape in the presence of an appropriate stimulus. This property allows these materials to be used as shape-memory artificial muscles, which form a subclass of artificial muscles. The shape-memory artificial muscles are fabricated from shape-memory polymers (SMPs) by twist insertion, shape fixation via T(m)or T-g, or by liquid crystal elastomers (LCEs). The prepared SMP artificial muscles can be used in a wide range of applications, from biomimetic and soft robotics to actuators, because they can be operated without sophisticated linkage design and can achieve complex final shapes. Recently, significant achievements have been made in fabrication, modelling, and manipulation of SMP-based artificial muscles. This paper presents a review of the recent progress in shape-memory polymer-based artificial muscles. Here we focus on the mechanisms of SMPs, applications of SMPs as artificial muscles, and the challenges they face concerning actuation. While shape-memory behavior has been demonstrated in several stimulated environments, our focus is on thermal-, photo-, and electrical-actuated SMP artificial muscles.
  •  
44.
  • Cheregi, Otilia, et al. (författare)
  • Regulation of the scp Genes in the Cyanobacterium Synechocystis sp PCC 6803-What is New?
  • 2015
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 20:8, s. 14621-14637
  • Tidskriftsartikel (refereegranskat)abstract
    • In the cyanobacterium Synechocystis sp. PCC 6803 there are five genes encoding small CAB-like (SCP) proteins, which have been shown to be up-regulated under stress. Analyses of the promoter sequences of the scp genes revealed the existence of an NtcA binding motif in two scp genes, scpB and scpE. Binding of NtcA, the key transcriptional regulator during nitrogen stress, to the promoter regions was shown by electrophoretic mobility shift assay. The metabolite 2-oxoglutarate did not increase the affinity of NtcA for binding to the promoters of scpB and scpE. A second motif, the HIP1 palindrome 5' GGCGATCGCC 3', was detected in the upstream regions of scpB and scpC. The transcription factor encoded by sll1130 has been suggested to recognize this motif to regulate heat-responsive genes. Our data suggest that HIP1 is not a regulatory element within the scp genes. Further, the presence of the high light regulatory (HLR1) motif was confirmed in scpB-E, in accordance to their induced transcriptions in cells exposed to high light. The HLR1 motif was newly discovered in eight additional genes.
  •  
45.
  • Chinnapaiyan, Maheswari, et al. (författare)
  • Nanotechnology, Green Synthesis and Biological Activity Application of Zinc Oxide Nanoparticles Incorporated Argemone Mxicana Leaf Extract
  • 2022
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 27:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanomaterial is a rapidly growing area that is used to create a variety of new materials and nanotechnology applications from medical, pharmaceuticals, chemical, mechanical, electronics and several environmental industries including physical, chemical and biological nanoparticles are very important in our daily life. Nanoparticles with leaf extract from the healthy plant are important in the area of research using biosynthesis methods. Because of it's used as an environmentally ecofriendly, other than traditional physical and chemical strategies. In particular, biologically synthesized nanoparticles have become a key branch of nanotechnology. The present work presents a synthesis of zinc oxide nanoparticles using an extract from the Argemone leaf Mexicana. Biosynthetic nanoparticles are characterized by X-ray diffraction (XRD), Ultraviolet visible (UV-vis) spectroscopy analysis, a Fourier Transform Infrared Spectroscopy analysis (FTIR) and a scanning electron microcopy (SEM), X-ray analysis with dispersive energy (EDAX). XRD is used to examine the crystalline size of zinc oxide nanoparticles. The FTIR test consists in providing evidence of the presence of targeted teams. UV is used for optical properties and calculates the energy of the bandwidth slot. The scanning microscope emission reveals the morphology of the surface and the energy dispersive X-ray analysis confirms the basic composition of zinc oxide nanoparticles. It is found that zinc nanoparticles are capable of achieving high anti-fungal efficacy and therefore have a high potential antimicrobial activity of ZnO NPs, like antibacterial and high antioxidant. Zinc Oxide nanoparticles from the Argemone Mexicana leaf extract have several antimicrobial applications, such as medical specialty, cosmetics, food, biotechnology, nano medicine and drug delivery system. ZnO nanoparticles are important because they provide many practical applications in industry. The most important use of nanoparticles of ZnO would be strong antibacterial and antioxidant activity with a simple and efficient biosynthesis method may be used for future work applications.
  •  
46.
  • Cunico, Larissa P., et al. (författare)
  • Solubility and Thermal Degradation of Quercetin in CO2-Expanded Liquids
  • 2020
  • Ingår i: Molecules (Basel, Switzerland). - : MDPI AG. - 1420-3049. ; 25:23
  • Tidskriftsartikel (refereegranskat)abstract
    • The solubility of quercetin and its thermal degradation was studied in CO2-expanded ethanol and ethyl lactate. An equipment setup was constructed that enabled the separation of the products of degradation while quantifying the solubility of quercetin. Three different conditions of temperature were analyzed (308, 323, and 343 K) at 10 MPa. Higher solubility and thermal degradation of quercetin were observed for CO2-expanded ethyl lactate in comparison with CO2-expanded ethanol. At the same time, as the amount of CO2 was increased in the CO2-expanded liquids mixtures, the thermal degradation of quercetin decreased for almost all the conditions of temperature considered in this work. The importance of considering thermal degradation while performing solubility measurements of compounds that are thermally unstable such as quercetin was highlighted.
  •  
47.
  • Czeiter, Endre, et al. (författare)
  • Calpain inhibition reduces axolemmal leakage in traumatic axonal injury
  • 2009
  • Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 14:12, s. 5115-5123
  • Tidskriftsartikel (refereegranskat)abstract
    • Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP) alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA) was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI. 
  •  
48.
  • Dahlgren, David, et al. (författare)
  • Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma : A Drug-Delivery Perspective
  • 2020
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 25:12
  • Forskningsöversikt (refereegranskat)abstract
    • Increased understanding of cancer biology, pharmacology and drug delivery has provided a new framework for drug discovery and product development that relies on the unique expression of specific macromolecules (i.e., antigens) on the surface of tumour cells. This has enabled the development of anti-cancer treatments that combine the selectivity of antibodies with the efficacy of highly potent chemotherapeutic small molecules, called antibody-drug conjugates (ADCs). ADCs are composed of a cytotoxic drug covalently linked to an antibody which then selectively binds to a highly expressed antigen on a cancer cell; the conjugate is then internalized by the cell where it releases the potent cytotoxic drug and efficiently kills the tumour cell. There are, however, many challenges in the development of ADCs, mainly around optimizing the therapeutic/safety benefits. These challenges are discussed in this review; they include issues with the plasma stability and half-life of the ADC, its transport from blood into and distribution throughout the tumour compartment, cancer cell antigen expression and the ADC binding affinity to the target antigen, the cell internalization process, cleaving of the cytotoxic drug from the ADC, and the cytotoxic effect of the drug on the target cells. Finally, we present a summary of some of the experimental ADC strategies used in the treatment of hepatocellular carcinoma, from the recent literature.
  •  
49.
  • Dahlgren, Markus K, et al. (författare)
  • Synthesis of 2-(2-Aminopyrimidine)-2,2-difluoroethanols as Potential Bioisosters of Salicylidene Acylhydrazides
  • 2010
  • Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 15:6, s. 4207-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Salicylidene acylhydrazides are inhibitors of type III secretion in several Gramnegative pathogens. To further develop the salicylidene acylhydrazides, scaffold hopping was applied to replace the core fragment of the compounds. The novel 2-(2-aminopyrimidine)-2,2-difluoroethanol scaffold was identified as a possible analog to thesalicylidene acylhydrazide core structure. The synthesis of a library of 2-(2-aminopyrimidine)-2,2-difluoro-ethanols is described in this paper.
  •  
50.
  • Dahlqvist, Alexander, et al. (författare)
  • 3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-Sites for High-Affinity and High-Selectivity Inhibition of Galectin-3
  • 2019
  • Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 24:24
  • Tidskriftsartikel (refereegranskat)abstract
    • The galectins are a family of galactose-binding proteins playing key roles in inflammatory processes and cancer. However, they are structurally very closely related, and discovery of highly selective inhibitors is challenging. In this work, we report the design of novel inhibitors binding to a subsite unique to galectin-3, which confers both high selectivity and affinity towards galectin-3. Olefin cross metathesis between allyl β-C-galactopyranosyl and 1-vinylnaphthalenes or acylation of aminomethyl β-C-galactopyranosyl with 1-naphthoic acid derivatives gave C-galactopyranosyls carrying 1-naphthamide structural elements that interacted favorably with a galectin-3 unique subsite according to molecular modeling and X-ray structural analysis of two inhibitor-galectin-3 complexes. Affinities were down to sub-µM and selectivities over galectin-1, 2, 4 N-terminal domain, 4 C-terminal domain, 7, 8 N-terminal domain, 9 N-terminal domain, and 9 C-terminal domain were high. These results show that high affinity and selectivity for a single galectin can be achieved by targeting unique subsites, which holds promise for further development of small and selective galectin inhibitors.
  •  
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