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Molecules, Volume 22, Issue 12 (December 2017)

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Editorial

Jump to: Research, Review, Other

Open AccessEditorial Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospective
Molecules 2017, 22(12), 2124; doi:10.3390/molecules22122124
Received: 20 November 2017 / Revised: 29 November 2017 / Accepted: 29 November 2017 / Published: 2 December 2017
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Abstract
In 2017, the 200th anniversary of the discovery of selenium was celebrated. In 1817, the Swedish chemists, Berzelius and Gahn, on roasting 200 kg of sulfur from a pyrite from the Falun mine, obtained about 3 g of a precipitate that they first
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In 2017, the 200th anniversary of the discovery of selenium was celebrated. In 1817, the Swedish chemists, Berzelius and Gahn, on roasting 200 kg of sulfur from a pyrite from the Falun mine, obtained about 3 g of a precipitate that they first wrongly identified as tellurium. Berzelius doubted this result and repeated the analysis some months later realizing that a new element was in his hands and he named this element Selenium (Greek: Selene, moon) in consideration of its resemblance to Tellurium (Latin: Tellus, earth). Several events were organized in the year for this special celebration and this Special Issue would like to be an additional contribution to the success of a research that, especially during the last decades, rapidly grew in different fields: synthesis, medicinal chemistry, biology, material, and environment. These studies are strongly characterized by multi- and interdisciplinary connections, and, for this reason, we collected here contributions coming from different areas and disciplines, not exclusively synthetic organic chemistry. Full article
Open AccessFeature PaperEditorial Peptide-Based Drugs and Drug Delivery Systems
Molecules 2017, 22(12), 2185; doi:10.3390/molecules22122185
Received: 5 December 2017 / Revised: 5 December 2017 / Accepted: 6 December 2017 / Published: 8 December 2017
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(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
Open AccessFeature PaperEditorial Photorelaxation and Photorepair Processes in Nucleic and Amino Acid Derivatives
Molecules 2017, 22(12), 2203; doi:10.3390/molecules22122203
Received: 5 December 2017 / Revised: 7 December 2017 / Accepted: 9 December 2017 / Published: 12 December 2017
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Abstract
Understanding the fundamental interaction between electromagnetic radiation and matter is essential for a large number of phenomena, with significance to civilization.[...] Full article
(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

Research

Jump to: Editorial, Review, Other

Open AccessArticle Response of Ustilago maydis against the Stress Caused by Three Polycationic Chitin Derivatives
Molecules 2017, 22(12), 1745; doi:10.3390/molecules22121745
Received: 10 August 2017 / Revised: 9 October 2017 / Accepted: 13 October 2017 / Published: 7 December 2017
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Abstract
Chitosan is a stressing molecule that affects the cells walls and plasma membrane of fungi. For chitosan derivatives, the action mode is not clear. In this work, we used the yeast Ustilago maydis to study the effects of these molecules on the plasma
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Chitosan is a stressing molecule that affects the cells walls and plasma membrane of fungi. For chitosan derivatives, the action mode is not clear. In this work, we used the yeast Ustilago maydis to study the effects of these molecules on the plasma membrane, focusing on physiologic and stress responses to chitosan (CH), oligochitosan (OCH), and glycol-chitosan (GCH). Yeasts were cultured with each of these molecules at 1 mg·mL−1 in minimal medium. To compare plasma membrane damage, cells were cultivated in isosmolar medium. Membrane potential (Δψ) as well as oxidative stress were measured. Changes in the total plasma membrane phospholipid and protein profiles were analyzed using standard methods, and fluorescence-stained mitochondria were observed. High osmolarity did not protect against CH inhibition and neither affected membrane potential. The OCH did produce higher oxidative stress. The effects of these molecules were evidenced by modifications in the plasma membrane protein profile. Also, mitochondrial damage was evident for CH and OCH, while GCH resulted in thicker cells with fewer mitochondria and higher glycogen accumulation. Full article
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Open AccessArticle Identification, In Vitro Testing and Molecular Docking Studies of Microginins’ Mechanism of Angiotensin-Converting Enzyme Inhibition
Molecules 2017, 22(12), 1884; doi:10.3390/molecules22121884
Received: 6 September 2017 / Revised: 1 October 2017 / Accepted: 10 October 2017 / Published: 5 December 2017
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Abstract
Cyanobacteria are able to produce a wide range of secondary metabolites, including toxins and protease inhibitors, with diverse biological activities. Microginins are small linear peptides biosynthesized by cyanobacteria species that act against proteases. The aim of this study was to isolate and identify
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Cyanobacteria are able to produce a wide range of secondary metabolites, including toxins and protease inhibitors, with diverse biological activities. Microginins are small linear peptides biosynthesized by cyanobacteria species that act against proteases. The aim of this study was to isolate and identify microginins produced by the LTPNA08 strain of Microcystis aeruginosa, as well as to verify their potential to inhibit angiotensin-converting enzyme (ACE; EC. 3.4.15.1) using in vitro and in silico methods. The fractionation of cyanobacterial extracts was performed by liquid chromatography and the presence of microginins was monitored by both LC-MS and an ACE inhibition assay. Enzyme inhibition was assayed by ACE with hippuryl-histidyl-leucine as the substrate; monitoring of hippuric acid was performed by HPLC-DAD. Isolated microginins were confirmed by mass spectrometry and were used to carry out the enzymatic assay. Molecular docking was used to evaluate microginin 770 (MG 770) and captopril (positive control), in order to predict similar binding interactions and determine the inhibitory action of ACE. The enzyme assay confirmed that MG 770 can efficiently inhibit ACE, with an IC50 equivalent to other microginins. MG 770 presented with comparable interactions with ACE, having features in common with commercial inhibitors such as captopril and enalaprilate, which are frequently used in the treatment of hypertension in humans. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Novel Method to Improve the Anticancer Activity of Natural-Based Hydroxyapatite against the Liver Cancer Cell Line HepG2 Using Mesoporous Magnesia as a Micro-Carrier
Molecules 2017, 22(12), 1947; doi:10.3390/molecules22121947
Received: 29 September 2017 / Revised: 30 October 2017 / Accepted: 8 November 2017 / Published: 24 November 2017
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Abstract
Micro-carriers are the best known vehicles to transport different kinds of drugs to achieve high impact. In this study, mesoporous magnesium oxide has been harnessed as a micro-carrier to encapsulate the anticancer candidate drug natural-based cubic hydroxyapatite (HAP). HAP@MgO composites with different HAP
[...] Read more.
Micro-carriers are the best known vehicles to transport different kinds of drugs to achieve high impact. In this study, mesoporous magnesium oxide has been harnessed as a micro-carrier to encapsulate the anticancer candidate drug natural-based cubic hydroxyapatite (HAP). HAP@MgO composites with different HAP loading (0–60 wt %), were prepared by a hydrothermal treatment method using triethanol amine as a template. The characterization of the prepared composites were achieved by using XRD, Raman spectroscopy, FTIR and SEM. Characterization data confirm the formation of sphere-like structures of MgO containing HAP particles. It was observed that the size of the spheres increased with HAP loading up to 40 wt %, then collapsed. Furthermore, the anticancer property of the prepared composites was evaluated against the HepG2 liver cancer cell line. The HAP@MgO composites exhibited higher activity than neat MgO or HAP. The 20 wt % of HAP was the optimum loading to control cell proliferation by inducing apoptosis. Apoptosis was determined by typical apoptotic bodies produced by the cell membrane. Full article
(This article belongs to the Special Issue New Drug Delivery System)
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Open AccessArticle Xanthones and Quinolones Derivatives Produced by the Deep-Sea-Derived Fungus Penicillium sp. SCSIO Ind16F01
Molecules 2017, 22(12), 1999; doi:10.3390/molecules22121999
Received: 16 October 2017 / Revised: 8 November 2017 / Accepted: 16 November 2017 / Published: 7 December 2017
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Abstract
Chemical investigation of the fungus Penicillium sp. SCSIO Ind16F01 derived from deep-sea sediment sample afforded a new xanthone, 3,8-dihydroxy-2-methyl-9-oxoxanthene-4-carboxylic acid methyl ester (1) and a new chromone, coniochaetone J (2), together with three known xanthones, 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid
[...] Read more.
Chemical investigation of the fungus Penicillium sp. SCSIO Ind16F01 derived from deep-sea sediment sample afforded a new xanthone, 3,8-dihydroxy-2-methyl-9-oxoxanthene-4-carboxylic acid methyl ester (1) and a new chromone, coniochaetone J (2), together with three known xanthones, 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (3), 7,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (4), 1,6,8-trihydroxy-3-(hydroxymethyl)anthraquinone (5), three known chromones, coniochaetone B (6), citrinolactones B (7), epiremisporine B (8), and four reported rare class of N-methyl quinolone lactams: quinolactacins B (9), C1 (10), and C2 (11), and quinolonimide (12). The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. Those isolated compounds were evaluated for their antiviral (EV71 and H3N2) and cytotoxic activities. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Design, Synthesis and Bioactivities of Novel Isoxazole-Containing Pyrazole Oxime Derivatives
Molecules 2017, 22(12), 2000; doi:10.3390/molecules22122000
Received: 9 November 2017 / Revised: 24 November 2017 / Accepted: 24 November 2017 / Published: 27 November 2017
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Abstract
In this study, in order to find novel biologically active pyrazole oxime derivatives, twenty-eight new pyrazole oxime compounds containing a substituted isoxazole ring were synthesized and evaluated for their acaricidaland insecticidal activities. Bioassays exhibited that some target compounds indicated good acaricidal and insecticidal
[...] Read more.
In this study, in order to find novel biologically active pyrazole oxime derivatives, twenty-eight new pyrazole oxime compounds containing a substituted isoxazole ring were synthesized and evaluated for their acaricidaland insecticidal activities. Bioassays exhibited that some target compounds indicated good acaricidal and insecticidal activities against Tetranychus cinnabarinus, Aphis medicaginis, Mythimna separata, and Nilaparvata lugens. Especially, compounds 9c, 9h, 9u, and 9v showed 100.00%, 90.56%, 90.78%, and 90.62% insecticidal activities against A. medicaginis at the concentration of 20 μg/mL, respectively, compounds 9k and 9u had 70.86% and 100.00% insecticidal activities against M. separata at 20 μg/mL, respectively. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle A Strategy for Preparative Separation of 10 Lignans from Justicia procumbens L. by High-Speed Counter-Current Chromatography
Molecules 2017, 22(12), 2024; doi:10.3390/molecules22122024
Received: 31 October 2017 / Revised: 18 November 2017 / Accepted: 20 November 2017 / Published: 23 November 2017
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Abstract
Ten compounds, including three lignan glycosides and seven lignans, were purified from Justicia procumbens L. in 8 h using an efficient strategy based on high-speed counter-current chromatography (HSCCC). The two-phase solvent system composed of petroleum–ethyl acetate–methanol–H2O (1:0.7:1:0.7, v/v)
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Ten compounds, including three lignan glycosides and seven lignans, were purified from Justicia procumbens L. in 8 h using an efficient strategy based on high-speed counter-current chromatography (HSCCC). The two-phase solvent system composed of petroleum–ethyl acetate–methanol–H2O (1:0.7:1:0.7, v/v) was firstly employed to separate the crude extract (320 mg), from which 19.3 mg of justicidin B (f), 10.8 mg of justicidin A (g), 13.9 mg of 6′-hydroxyjusticidin C (h), 7.7 mg of justicidin E (i), 6.3 mg of lignan J1 (j) were obtained with 91.3 mg of enriched mixture of compounds ae. The enriched mixture (91.3 mg) was further separated using the solvent system consisting of petroleum–ethyl acetate–methanol–H2O (3:3.8:3:3.8, v/v), yielding 12.1 mg of procumbenoside E (a); 7.6 mg of diphyllin-1-O-β-d-apiofuranoside (b); 7.4 mg of diphyllin (c); 8.3 mg of 6′-hydroxy justicidin B (d); and 7.9 mg of diphyllin acetyl apioside (e). The purities of the 10 components were all above 94%, and their structures were identified by NMR and ESI-MS spectra. The results demonstrated that the strategy based on HSCCC for the separation of lignans and their glycosides was efficient and rapid. Full article
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Open AccessArticle Hydroboration-Oxidation of (±)-(1α,3α,3aβ,6aβ) -1,2,3,3a,4,6a-Hexahydro-1,3-pentalenedimethanol and Its O-Protected Derivatives: Synthesis of New Compounds Useful for Obtaining (iso)Carbacyclin Analogues and X-ray Analysis of the Products
Molecules 2017, 22(12), 2032; doi:10.3390/molecules22122032
Received: 22 October 2017 / Revised: 15 November 2017 / Accepted: 16 November 2017 / Published: 24 November 2017
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Abstract
Hydroboration-oxidation of 2α,4α-dimethanol-1β,5β-bicyclo[3.3.0]oct-6-en dibenzoate (1) gave alcohols 2 (symmetric) and 3 (unsymmetric) in ~60% yield, together with the monobenzoate diol 4a (37%), resulting from the reduction of the closer benzoate by the intermediate alkylborane. The corresponding alkene and dialdehyde gave only
[...] Read more.
Hydroboration-oxidation of 2α,4α-dimethanol-1β,5β-bicyclo[3.3.0]oct-6-en dibenzoate (1) gave alcohols 2 (symmetric) and 3 (unsymmetric) in ~60% yield, together with the monobenzoate diol 4a (37%), resulting from the reduction of the closer benzoate by the intermediate alkylborane. The corresponding alkene and dialdehyde gave only the triols 8 and 9 in ~1:1 ratio. By increasing the reaction time and the temperature, the isomerization of alkylboranes favours the un-symmetrical triol 9. The PDC oxidation of the alcohols gave cleanly the corresponding ketones 5 and 6 and the deprotection of the benzoate groups gave the symmetrical ketone 14, and the cyclic hemiketal 15, all in high yields. The ethylene ketals of the symmetrical ketones 11 and 13 were also obtained. The compounds 5, 6, 11, 13, 14 could be used for synthesis of new (iso)carbacyclin analogues. The structure of the compounds was established by NMR spectroscopy and confirmed by X-ray crystallography. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis and Evaluation of Thiochroman-4-One Derivatives as Potential Leishmanicidal Agents
Molecules 2017, 22(12), 2041; doi:10.3390/molecules22122041
Received: 24 October 2017 / Revised: 20 November 2017 / Accepted: 20 November 2017 / Published: 29 November 2017
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Abstract
The S-containing heterocyclic compounds benzothiopyrans or thiochromones stand out as having promising biological activities due to their structural relationship with chromones (benzopyrans), which are widely known as privileged scaffolds in medicinal chemistry. In this work, we report the synthesis of 35 thiochromone derivatives
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The S-containing heterocyclic compounds benzothiopyrans or thiochromones stand out as having promising biological activities due to their structural relationship with chromones (benzopyrans), which are widely known as privileged scaffolds in medicinal chemistry. In this work, we report the synthesis of 35 thiochromone derivatives and the in vitro antileishmanial and cytotoxic activities. Compounds were tested against intracellular amastigotes of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Compounds bearing a vinyl sulfone moiety, 4h, 4i, 4j, 4k, 4l and 4m, displayed the highest antileishmanial activity, with EC50 values lower than 10 μM and an index of selectivity over 100 for compounds 4j and 4l. When the double bond or the sulfone moiety was removed, the activity decreased. Our results show that thiochromones bearing a vinyl sulfone moiety are endowed with high antileishmanial activity and low cytotoxicity. Full article
(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)
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Open AccessArticle Optimization of Dissolution Compartments in a Biorelevant Dissolution Apparatus Golem v2, Supported by Multivariate Analysis
Molecules 2017, 22(12), 2042; doi:10.3390/molecules22122042
Received: 27 September 2017 / Accepted: 20 November 2017 / Published: 23 November 2017
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Abstract
Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for
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Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus—Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility. Full article
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Open AccessArticle Impact of Ohmic-Assisted Decoction on Bioactive Components Extracted from Yacon (Smallanthus sonchifolius Poepp.) Leaves: Comparison with Conventional Decoction
Molecules 2017, 22(12), 2043; doi:10.3390/molecules22122043
Received: 29 October 2017 / Revised: 19 November 2017 / Accepted: 21 November 2017 / Published: 23 November 2017
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Abstract
Yacon (Smallanthus sonchifolius Poepp.) leaves are a potentially rich source of bioactive compounds, such as phenolic acids and flavonoids. In this study, the effect of the extraction method (ohmic-assisted decoction (OH-DE) and decoction (DE)), yacon cultivar (red and white), and leaf age
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Yacon (Smallanthus sonchifolius Poepp.) leaves are a potentially rich source of bioactive compounds, such as phenolic acids and flavonoids. In this study, the effect of the extraction method (ohmic-assisted decoction (OH-DE) and decoction (DE)), yacon cultivar (red and white), and leaf age (young and old) on the quality/quantity of extracted phytochemicals were investigated. Extraction yield, energy consumption, total phenolic content (TPC), total flavonoid content (TFC), ABTS and DPPH radical scavenging activity, and ferric reducing antioxidant power (FRAP) were determined. Additionally, HPLC-DAD was used to identify the major individual phenolic and flavonoid compounds of yacon leaves. The results showed that a three-way interaction of process-variables (extraction method×yacon cultivar×age of leaves) influenced the extraction yield, TPC, TFC, ABTS, and DPPH radical scavenging activity, and FRAP, significantly (p < 0.05). However, energy consumption of the extraction process was only affected by method of extraction (p < 0.05) and was halved when OH-DE was applied as compared to DE alone. Additionally, the phytochemical quality of extracts was either improved or comparable when OH-DE was used for extraction. Also, it was shown that yacon leaves contained considerable amounts of caffeic acid, chlorogenic acid, ferrulic acid, myricetin, p-coumaric acid, and rutin, while leaves of the red cultivar had higher contents of each compound compared to leaves of the white cultivar. Full article
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Open AccessArticle Recyclable Magnetic Titania Nanocomposite from Ilmenite with Enhanced Photocatalytic Activity
Molecules 2017, 22(12), 2044; doi:10.3390/molecules22122044
Received: 19 October 2017 / Revised: 9 November 2017 / Accepted: 20 November 2017 / Published: 23 November 2017
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Abstract
Using ilmenite as a raw material, iron was converted into Fe3O4 magnetic fluid, which further was combined with titanium filtrate by a solvothermal method. Finally Fe3O4/TiO2 nanocomposites with the uniform size of 100–200 nm were
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Using ilmenite as a raw material, iron was converted into Fe3O4 magnetic fluid, which further was combined with titanium filtrate by a solvothermal method. Finally Fe3O4/TiO2 nanocomposites with the uniform size of 100–200 nm were prepared. This approach uses rich, inexpensive ilmenite as a titanium and iron source, which effectively reduces the production cost. The crystal structure, chemical properties and morphologies of the products were characterized by SEM, TEM, XRD, FTIR, BET, UV-Vis, XPS and VSM. The novel photocatalyst composed of face-centered cubic Fe3O4 and body-centered tetragonal anatase–TiO2 exhibits a spherical shape with porous structures, superparamagnetic behavior and strong absorption in the visible light range. Using the degradation reaction of Rhodamine B (RhB) to evaluate the photocatalytic performance, the results suggest that Fe3O4/TiO2 nanocomposites exhibit excellent photocatalytic activities and stability under visible light and solar light. Moreover, the magnetic titania nanocomposites displayed good magnetic response and were recoverable over several cycles. Based on the trapping experiments, the main active species in the photocatalytic reaction were confirmed and the possible photocatalytic mechanism of RhB with magnetic titania was proposed. The enhanced photocatalytic activity and stability, combined with excellent magnetic recoverability, make the prepared nanocomposite a potential candidate in wastewater purification. Full article
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Open AccessArticle Enological Tannin Effect on Red Wine Color and Pigment Composition and Relevance of the Yeast Fermentation Products
Molecules 2017, 22(12), 2046; doi:10.3390/molecules22122046
Received: 19 September 2017 / Revised: 14 November 2017 / Accepted: 21 November 2017 / Published: 23 November 2017
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Abstract
Enological tannins are widely used in the winemaking process either to improve different wine characteristics (color stability, among others) or to compensate for low tannin levels. In this work, the influence of the addition of two different enological tannins, mainly composed of hydrolysable
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Enological tannins are widely used in the winemaking process either to improve different wine characteristics (color stability, among others) or to compensate for low tannin levels. In this work, the influence of the addition of two different enological tannins, mainly composed of hydrolysable (ellagitannins) and condensed tannins, on the evolution of color and pigment composition of two different types of model systems containing the five main grape anthocyanins was studied. In addition, the effect of the addition of an enological tannin on the color and pigment composition of red wines made from Vitis vinifera L. cv Tempranillo grapes was also studied by high-performance liquid chromatography with diode array detection coupled to mass spectrometry (HPLC-DAD-MS). Results showed that, in model systems, the addition of the enological tannin favored the formation of anthocyanin-derived pigments, such as A-type and B-type vitisins and flavanol-anthocyanin condensation products, provided that the yeast precursors were previously supplied. Moreover, model systems containing the enological tannins were darker and showed higher values of chroma at the end of the study than control ones. The higher formation of these anthocyanin-derived pigments was also observed in the red wines containing the enological tannin. Moreover, these wine also showed lower lightness (L*) values and higher chroma (C*ab) values than control wines, indicating a higher stabilization of color. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle Study on the Anticoagulant or Procoagulant Activities of Type II Phenolic Acid Derivatives
Molecules 2017, 22(12), 2047; doi:10.3390/molecules22122047
Received: 20 September 2017 / Revised: 13 November 2017 / Accepted: 21 November 2017 / Published: 28 November 2017
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Abstract
In this study, three type II phenolic acids (caffeic acid, p-hydroxycinnamic acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid derivatives. With molecular docking for molecule design and target protein (factors) screening, in combination with the confirmation
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In this study, three type II phenolic acids (caffeic acid, p-hydroxycinnamic acid, and ferulic acid) were used to synthesize a total of 18 phenolic acid derivatives. With molecular docking for molecule design and target protein (factors) screening, in combination with the confirmation of target proteins (factors) by surface plasmon resonance, and the evaluation of haemostatic and anticoagulant activities with five blood assays (plasma recalcification time, prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time), the data indicated that caffeic acid derivatives showed certain anticoagulant or procoagulant activities and that two other series contained compounds with the best anticoagulant activities. Using Materials Studio analysis, particular functional groups that affect anticoagulant or procoagulant activities were revealed, and these conclusions can guide the discovery of compounds with better activities. Full article
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Open AccessArticle Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts
Molecules 2017, 22(12), 2048; doi:10.3390/molecules22122048
Received: 30 September 2017 / Revised: 8 November 2017 / Accepted: 21 November 2017 / Published: 23 November 2017
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Abstract
Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The
[...] Read more.
Tertiary amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa) and lipophilicity index (log P) of tertiary amines were determined; while quaternary ammonium salts were characterized by software-calculated lipophilicity index and surface tension. Biological evaluation aimed at testing acetylcholinesterase and butyrylcholinesterase-inhibiting activity of synthesized compounds. A possible mechanism of action of these compounds was determined by molecular modelling study using combined techniques of docking; molecular dynamics simulations and quantum mechanics calculations. Full article
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Open AccessArticle Modulation of Cytochrome P450, P-glycoprotein and Pregnane X Receptor by Selected Antimalarial Herbs—Implication for Herb-Drug Interaction
Molecules 2017, 22(12), 2049; doi:10.3390/molecules22122049
Received: 30 October 2017 / Accepted: 20 November 2017 / Published: 23 November 2017
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Abstract
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19,
[...] Read more.
Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells. The inhibition of P-gp activity was determined as a reflection of increase in calcein-AM uptake. Additionally, the enzyme induction potential of the extracts was assessed through the modulation of PXR activity in HepG2 cells transiently transfected with pSG5-PXR and PCR5 plasmid DNA. Significant inhibition of CYP activity (IC50 < 10 µg/mL) was observed with the following herbs: A. muricata [CYP2C9, 3A4 and CYP2D6]; M. indica [CYP2C9]; M. charantia [CYP2C9 and CYP2C19]; P. amarus [CYP2C19, CYP2C9 and CYP3A4]; T. diversifolia [CYP2C19 and CYP3A4]. Extracts of four herbs (P. amarus, M. charantia, T. diversifolia and A. muricata) exhibited significant inhibition of P-gp with IC50 values (µg/mL) of 17 ± 1, 16 ± 0.4, 26 ± 1, and 24 ± 1, respectively. In addition, four herbs (A. mexicana, M. charantia, P. amarus and T. diversifolia) showed a >two-fold increase in induction in PXR activity. These findings suggest that these herbs may be capable of eliciting herb-drug interactions if consumed in high quantities with concomitant use of conventional therapies. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives
Molecules 2017, 22(12), 2051; doi:10.3390/molecules22122051
Received: 31 October 2017 / Revised: 20 November 2017 / Accepted: 21 November 2017 / Published: 23 November 2017
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Abstract
Azole-based antifungal agents constitute one of the important classes of antifungal drugs. Hence, in the present work, 12 new benzimidazole-thiazole derivatives 3a3l were synthesized to evaluate their anticandidal activity against C. albicans, C. glabrata, C. krusei, and C.
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Azole-based antifungal agents constitute one of the important classes of antifungal drugs. Hence, in the present work, 12 new benzimidazole-thiazole derivatives 3a3l were synthesized to evaluate their anticandidal activity against C. albicans, C. glabrata, C. krusei, and C. parapsilopsis. The structures of the newly synthesized compounds 3a3l were confirmed by IR, 1H-NMR, 13C-NMR, and ESI-MS spectroscopic methods. ADME parameters of synthesized compounds 3a3l were predicted by an in-slico study and it was determined that all synthesized compounds may have a good pharmacokinetic profile. In the anticandidal activity studies, compounds 3c and 3d were found to be the most active compounds against all Candida species. In addition, cytoxicity studies showed that these compounds are nontoxic with a IC50 value higher than 500 µg/mL. The effect of compounds 3c and 3d on the ergosterol level of C. albicans was determined by an LC-MS-MS method. It was observed that both compounds cause a decrease in the ergosterol level. A molecular docking study including binding modes of 3c to lanosterol 14α-demethylase (CYP51), a key enzyme in ergosterol biosynthesis, was performed to elucidate the mechanism of the antifungal action. The docking studies revealed that there is a strong interaction between CYP51 and the most active compound 3c. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessArticle Neurotoxic Effects of Linalool and β-Pinene on Tribolium castaneum Herbst
Molecules 2017, 22(12), 2052; doi:10.3390/molecules22122052
Received: 9 September 2017 / Accepted: 21 November 2017 / Published: 24 November 2017
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Abstract
Effective, ethical pest control requires the use of chemicals that are highly specific, safe, and ecofriendly. Linalool and β-pinene occur naturally as major constituents of the essential oils of many plant species distributed throughout the world, and thus meet these requirements. These monoterpenes
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Effective, ethical pest control requires the use of chemicals that are highly specific, safe, and ecofriendly. Linalool and β-pinene occur naturally as major constituents of the essential oils of many plant species distributed throughout the world, and thus meet these requirements. These monoterpenes were tested as repellents against Tribolium castaneum, using the area preference method, after four hours of exposure and the effect transcriptional of genes associated with neurotransmission. Changes in gene expression of acetylcholinesterase (Ace1), GABA-gated anion channel splice variant 3a6a (Rdl), GABA-gated ion channel (Grd), glutamate-gated chloride channel (Glucl), and histamine-gated chloride channel 2 (Hiscl2) were assessed and the interaction with proteins important for the insect using in silico methods was also studied. For linalool and β-pinene, the repellent concentration 50 (RC50) values were 0.11 µL/cm2 and 0.03 µL/cm2, respectively. Both compounds induced overexpression of Hiscl2 gen in adult insects, and β-pinene also promoted the overexpression of Grd and the Ace1 gene. However, β-pinene and linalool had little potential to dock on computer-generated models for GABA-gated ion channel LCCH3, nicotinic acetylcholine receptor subunits alpha1 and alpha2, and putative octopamine/tyramine receptor proteins from T. castaneum as their respective binding affinities were marginal, and therefore the repellent action probably involved mechanisms other than direct interaction with these targets. Results indicated that β-pinene was more potent than linalool in inducing insect repellency, and also had a greater capacity to generate changes in the expression of genes involved in neuronal transmission. Full article
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Open AccessArticle Antifungal Activity and Action Mode of Cuminic Acid from the Seeds of Cuminum cyminum L. against Fusarium oxysporum f. sp. Niveum (FON) Causing Fusarium Wilt on Watermelon
Molecules 2017, 22(12), 2053; doi:10.3390/molecules22122053
Received: 31 October 2017 / Revised: 10 November 2017 / Accepted: 21 November 2017 / Published: 30 November 2017
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Abstract
In order to develop a novel biofungicide, the antifungal activity and action mode of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f. sp. niveum (FON) on watermelon was determined systematically. In this study, the median effective concentration (EC
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In order to develop a novel biofungicide, the antifungal activity and action mode of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f. sp. niveum (FON) on watermelon was determined systematically. In this study, the median effective concentration (EC50) value for cuminic acid in inhibiting mycelial growth of FON was 22.53 μg/mL. After treatment with cuminic acid, the mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid) were significantly decreased. Synthesis genes of bikaverin (Bike1, Bike2 and Bike3) and fusaric acid (FUB1, FUB2, FUB3 and FUB4) both were downregulated compared with the control, as confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content were observed after in vivo cuminic acid treatment on watermelon leaves. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Deep Convolutional Neural Network-Based Early Automated Detection of Diabetic Retinopathy Using Fundus Image
Molecules 2017, 22(12), 2054; doi:10.3390/molecules22122054
Received: 10 November 2017 / Revised: 20 November 2017 / Accepted: 22 November 2017 / Published: 23 November 2017
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Abstract
The automatic detection of diabetic retinopathy is of vital importance, as it is the main cause of irreversible vision loss in the working-age population in the developed world. The early detection of diabetic retinopathy occurrence can be very helpful for clinical treatment; although
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The automatic detection of diabetic retinopathy is of vital importance, as it is the main cause of irreversible vision loss in the working-age population in the developed world. The early detection of diabetic retinopathy occurrence can be very helpful for clinical treatment; although several different feature extraction approaches have been proposed, the classification task for retinal images is still tedious even for those trained clinicians. Recently, deep convolutional neural networks have manifested superior performance in image classification compared to previous handcrafted feature-based image classification methods. Thus, in this paper, we explored the use of deep convolutional neural network methodology for the automatic classification of diabetic retinopathy using color fundus image, and obtained an accuracy of 94.5% on our dataset, outperforming the results obtained by using classical approaches. Full article
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Open AccessArticle Species-Specific Inactivation of Triosephosphate Isomerase from Trypanosoma brucei: Kinetic and Molecular Dynamics Studies
Molecules 2017, 22(12), 2055; doi:10.3390/molecules22122055
Received: 7 November 2017 / Revised: 19 November 2017 / Accepted: 21 November 2017 / Published: 24 November 2017
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Abstract
Human African Trypanosomiasis (HAT), a disease that provokes 2184 new cases a year in Sub-Saharan Africa, is caused by Trypanosoma brucei. Current treatments are limited, highly toxic, and parasite strains resistant to them are emerging. Therefore, there is an urgency to find
[...] Read more.
Human African Trypanosomiasis (HAT), a disease that provokes 2184 new cases a year in Sub-Saharan Africa, is caused by Trypanosoma brucei. Current treatments are limited, highly toxic, and parasite strains resistant to them are emerging. Therefore, there is an urgency to find new drugs against HAT. In this context, T. brucei depends on glycolysis as the unique source for ATP supply; therefore, the enzyme triosephosphate isomerase (TIM) is an attractive target for drug design. In the present work, three new benzimidazole derivatives were found as TbTIM inactivators (compounds 1, 2 and 3) with an I50 value of 84, 82 and 73 µM, respectively. Kinetic analyses indicated that the three molecules were selective when tested against human TIM (HsTIM) activity. Additionally, to study their binding mode in TbTIM, we performed a 100 ns molecular dynamics simulation of TbTIM-inactivator complexes. Simulations showed that the binding of compounds disturbs the structure of the protein, affecting the conformations of important domains such as loop 6 and loop 8. In addition, the physicochemical and drug-like parameters showed by the three compounds suggest a good oral absorption. In conclusion, these molecules will serve as a guide to design more potent inactivators that could be used to obtain new drugs against HAT. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessArticle Drug-Target Interaction Prediction through Label Propagation with Linear Neighborhood Information
Molecules 2017, 22(12), 2056; doi:10.3390/molecules22122056
Received: 12 October 2017 / Revised: 19 November 2017 / Accepted: 20 November 2017 / Published: 25 November 2017
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Abstract
Interactions between drugs and target proteins provide important information for the drug discovery. Currently, experiments identified only a small number of drug-target interactions. Therefore, the development of computational methods for drug-target interaction prediction is an urgent task of theoretical interest and practical significance.
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Interactions between drugs and target proteins provide important information for the drug discovery. Currently, experiments identified only a small number of drug-target interactions. Therefore, the development of computational methods for drug-target interaction prediction is an urgent task of theoretical interest and practical significance. In this paper, we propose a label propagation method with linear neighborhood information (LPLNI) for predicting unobserved drug-target interactions. Firstly, we calculate drug-drug linear neighborhood similarity in the feature spaces, by considering how to reconstruct data points from neighbors. Then, we take similarities as the manifold of drugs, and assume the manifold unchanged in the interaction space. At last, we predict unobserved interactions between known drugs and targets by using drug-drug linear neighborhood similarity and known drug-target interactions. The experiments show that LPLNI can utilize only known drug-target interactions to make high-accuracy predictions on four benchmark datasets. Furthermore, we consider incorporating chemical structures into LPLNI models. Experimental results demonstrate that the model with integrated information (LPLNI-II) can produce improved performances, better than other state-of-the-art methods. The known drug-target interactions are an important information source for computational predictions. The usefulness of the proposed method is demonstrated by cross validation and the case study. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
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Open AccessArticle Simultaneous Determination of Multiple Classes of Hydrophilic and Lipophilic Components in Shuang-Huang-Lian Oral Liquid Formulations by UPLC-Triple Quadrupole Linear Ion Trap Mass Spectrometry
Molecules 2017, 22(12), 2057; doi:10.3390/molecules22122057
Received: 25 October 2017 / Revised: 12 November 2017 / Accepted: 23 November 2017 / Published: 24 November 2017
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Abstract
The Shuang-Huang-Lian (SHL) oral liquid is a combined herbal prescription used in the treatment of acute upper respiratory tract infection, acute bronchitis and pneumonia. Multiple constituents are considered to be responsible for the therapeutic effects of SHL. However, the quantitation of the multi-components
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The Shuang-Huang-Lian (SHL) oral liquid is a combined herbal prescription used in the treatment of acute upper respiratory tract infection, acute bronchitis and pneumonia. Multiple constituents are considered to be responsible for the therapeutic effects of SHL. However, the quantitation of the multi-components from multiple classes is still unsatisfactory because of the high complexity of constituents in SHL. In this study, an accurate, rapid, and specific UPLC-MS/MS method was established for simultaneous quantification of 18 compounds from multiple classes in SHL oral liquid formulations. Chromatographic separation was performed on a HSS T3 (1.8 μm, 2.1 mm × 100 mm) column, using a gradient mobile phase system of 0.1% formic acid in acetonitrile and 0.1% formic acid in water at a flow rate of 0.2 mL·min−1; the run time was 23 min. The MS was operated in negative electrospray ionization (ESI) for analysis of 18 compounds using multiple reaction monitoring (MRM) mode. UPLC-ESI-MRM-MS/MS method showed good linear relationships (R2 > 0.999), repeatability (RSD < 3%), precisions (RSD < 3%) and recovery (84.03–101.62%). The validated method was successfully used to determine multiple classes of hydrophilic and lipophilic components in the SHL oral liquids. Finally, principal component analysis (PCA) was used to classify and differentiate SHL oral liquid samples attributed to different manufacturers of China. The proposed UPLC-ESI-MRM-MS/MS coupled with PCA has been elucidated to be a simple and reliable method for quality evaluation of SHL oral liquids. Full article
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Open AccessArticle PTP1B Inhibitors from the Entomogenous Fungi Isaria fumosorosea
Molecules 2017, 22(12), 2058; doi:10.3390/molecules22122058
Received: 8 November 2017 / Revised: 22 November 2017 / Accepted: 23 November 2017 / Published: 24 November 2017
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Abstract
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Thus, small molecule inhibitors of PTP1B can be considered as
[...] Read more.
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Thus, small molecule inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes and cancer diseases. In a continuing search for new PTP1B inhibitors, a new tetramic acid possessing a rare pyrrolidinedione skeleton named fumosorinone A (1), together with five known ones 26 were isolated from the entomogenous fungus Isaria fumosorosea. The structures of 26 were elucidated by extensive spectroscopic analysis. Fumosorinone A (1) and beauvericin (6) showed significant PTP1B inhibitory activity with IC50 value of 3.24 μM and 0.59 μM. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results
Molecules 2017, 22(12), 2059; doi:10.3390/molecules22122059
Received: 19 October 2017 / Revised: 17 November 2017 / Accepted: 21 November 2017 / Published: 27 November 2017
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Abstract
The inferior oocytes (IOs), which are not suitable for embryo development, occupy roughly one-third or more of the collected immature bovine oocytes. The IOs are usually discarded from the in vitro bovine embryo production process. Improving the quality of the inferior oocytes (IOs)
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The inferior oocytes (IOs), which are not suitable for embryo development, occupy roughly one-third or more of the collected immature bovine oocytes. The IOs are usually discarded from the in vitro bovine embryo production process. Improving the quality of the inferior oocytes (IOs) and make them available in in vitro embryo production would have important biological, as well as commercial, value. This study was designed to investigate whether melatonin could improve the quality of IOs and make them usable in the in vitro maturation (IVM) and subsequent (in vitro fertilization) IVF embryo development. The results indicated that: the maturation rate of IOs and their subsequent IVF embryo developments were impaired compared to cumulus-oocyte complexes and melatonin treatment significantly improved the quality of IOs, as well as their IVF and embryo developments. The potential mechanisms are that: (1) melatonin reduced reactive oxygen species (ROS) and enhanced glutathione (GSH) levels in the IOs, thereby protecting them from oxidative stress; (2) melatonin improved mitochondrial normal distribution and function to increase ATP level in IOs; and (3) melatonin upregulated the expression of ATPase 6, BMP-15, GDF-9, SOD-1, Gpx-4, and Bcl-2, which are critical genes for oocyte maturation and embryo development and downregulated apoptotic gene expression of caspase-3. Full article
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Open AccessFeature PaperCommunication Connectivity and Topology Invariance in Self-Assembled and Halogen-Bonded Anionic (6,3)-Networks
Molecules 2017, 22(12), 2060; doi:10.3390/molecules22122060
Received: 24 October 2017 / Revised: 14 November 2017 / Accepted: 21 November 2017 / Published: 24 November 2017
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Abstract
We report here that the halogen bond driven self-assembly of 1,3,5-trifluorotriiodobenzene with tetraethylammonium and -phosphonium bromides affords 1:1 co-crystals, wherein the mutual induced fit of the triiodobenzene derivative and the bromide anions (halogen bond donor and acceptors, respectively) elicits the potential of these
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We report here that the halogen bond driven self-assembly of 1,3,5-trifluorotriiodobenzene with tetraethylammonium and -phosphonium bromides affords 1:1 co-crystals, wherein the mutual induced fit of the triiodobenzene derivative and the bromide anions (halogen bond donor and acceptors, respectively) elicits the potential of these two tectons to function as tritopic modules (6,3). Supramolecular anionic networks are present in the two co-crystals wherein the donor and the acceptor alternate at the vertexes of the hexagonal frames and cations are accommodated in the potential empty space encircled by the frames. The change of one component in a self-assembled multi-component co-crystal often results in a change in its supramolecular connectivity and topology. Our systems have the same supramolecular features of corresponding iodide analogues as the metric aspects seem to prevail over other aspects in controlling the self-assembly process. Full article
(This article belongs to the Special Issue Halogen Bonds and Beyond)
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Open AccessArticle Nitrogen-Doped Carbon Quantum Dots as Fluorescent Probes for Sensitive and Selective Detection of Nitrite
Molecules 2017, 22(12), 2061; doi:10.3390/molecules22122061
Received: 24 October 2017 / Revised: 22 November 2017 / Accepted: 24 November 2017 / Published: 24 November 2017
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Abstract
Nitrites are the upstream precursors of the carcinogenic nitrosamines, which are widely found in the natural environment and many food products. It is important to develop a simple and sensitive sensor for detecting nitrites. In this work, a fluorescence probe based on nitrogen-doped
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Nitrites are the upstream precursors of the carcinogenic nitrosamines, which are widely found in the natural environment and many food products. It is important to develop a simple and sensitive sensor for detecting nitrites. In this work, a fluorescence probe based on nitrogen-doped carbon quantum dots (N-CQDs) was developed for the sensitive and selective determination of nitrites. At pH 2, the fluorescence of N-CQDs can be selectively quenched by nitrite due to the fact N-nitroso compounds can be formed in the reaction of amide groups with nitrous acid, which results in fluorescence static quenching. Under optimal conditions, fluorescence intensity quenching upon addition of nitrite gives a satisfactory linear relationship covering the linear range of 0.2–20 μM, and the limit of detection (LOD) is 40 nM. Moreover, this method has been successfully applied to the determination of nitrites in tap water, which indicates its great potential for monitoring of nitrites in environmental samples. Full article
(This article belongs to the Section Analytical Chemistry)
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Open AccessArticle Terpenoids and Phenylpropanoids in Ligularia duciformis, L. kongkalingensis, L. nelumbifolia, and L. limprichtii
Molecules 2017, 22(12), 2062; doi:10.3390/molecules22122062
Received: 2 November 2017 / Revised: 22 November 2017 / Accepted: 23 November 2017 / Published: 25 November 2017
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Abstract
The diversity in root chemicals and evolutionally neutral DNA regions in the complex of Ligularia duciformis, L. kongkalingensis, and L. nelumbifolia (the d/k/n complex) was studied using eight samples collected in central and northern Sichuan Province of China. Cacalol (14
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The diversity in root chemicals and evolutionally neutral DNA regions in the complex of Ligularia duciformis, L. kongkalingensis, and L. nelumbifolia (the d/k/n complex) was studied using eight samples collected in central and northern Sichuan Province of China. Cacalol (14) and epicacalone (15), rearranged eremophilanes, were isolated from the complex for the first time. Two new phenylpropanoids were also obtained. Seven of the eight samples produced phenylpropanoids and the other produced lupeol alone. Two of the seven samples also produced furanoeremophilanes or their derivatives and one produced oplopanes. The geographical distribution of the sesquiterpene-producing populations suggests that the production of sesquiterpenes evolved independently in separate regions. L. limprichtii collected in northern Sichuan was also analyzed and its chemical composition and the sequence of internal transcribed spacers (ITSs) in the ribosomal RNA gene cluster were found to be similar to that in the d/k/n complex and L. yunnanensis, which are morphologically similar. Full article
(This article belongs to the Special Issue Diversity of Terpenoids)
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Open AccessArticle Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria
Molecules 2017, 22(12), 2063; doi:10.3390/molecules22122063
Received: 4 October 2017 / Revised: 21 November 2017 / Accepted: 23 November 2017 / Published: 25 November 2017
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Abstract
In addition to gap junctional channels that mediate cell-to-cell communication, connexins form hemichannels that are present at the plasma membrane. Since hemichannels are permeable to small hydrophilic compounds, including metabolites and signaling molecules, their abnormal opening can cause or contribute to cell damage
[...] Read more.
In addition to gap junctional channels that mediate cell-to-cell communication, connexins form hemichannels that are present at the plasma membrane. Since hemichannels are permeable to small hydrophilic compounds, including metabolites and signaling molecules, their abnormal opening can cause or contribute to cell damage in disorders such as cardiac infarct, stroke, deafness, skin diseases, and cataracts. Therefore, hemichannels are potential pharmacological targets. A few aminoglycosides, well-known broad-spectrum antibiotics, have been shown to inhibit hemichannels. Here, we tested several commercially available aminoglycosides for inhibition of human connexin hemichannels using a cell-based bacterial growth complementation assay that we developed recently. We found that kanamycin A, kanamycin B, geneticin, neomycin, and paromomycin are effective inhibitors of hemichannels formed by connexins 26, 43, and 46 (Cx26, Cx43, and Cx46). Because of the >70 years of clinical experience with aminoglycosides and the fact that several of the aminoglycosides tested here have been used in humans, they are promising starting points for the development of effective connexin hemichannel inhibitors. Full article
(This article belongs to the Special Issue Recent Development on the New Applications of Aminoglycosides)
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Open AccessArticle Antioxidative Categorization of Twenty Amino Acids Based on Experimental Evaluation
Molecules 2017, 22(12), 2066; doi:10.3390/molecules22122066
Received: 19 October 2017 / Revised: 16 November 2017 / Accepted: 23 November 2017 / Published: 27 November 2017
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Abstract
In view of the great importance bestowed on amino acids as antioxidants in oxidation resistance, we attempted two common redox titration methods in this report, including micro-potassium permanganate titration and iodometric titration, to measure the antioxidative capacity of 20 amino acids, which are
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In view of the great importance bestowed on amino acids as antioxidants in oxidation resistance, we attempted two common redox titration methods in this report, including micro-potassium permanganate titration and iodometric titration, to measure the antioxidative capacity of 20 amino acids, which are the construction units of proteins in living organisms. Based on the relative intensities of the antioxidative capacity, we further conducted a quantitative comparison and found out that the product of experimental values obtained from the two methods was proven to be a better indicator for evaluating the relative antioxidative capacity of amino acids. The experimental results were largely in accordance with structural analysis made on amino acids. On the whole, the 20 amino acids concerned could be divided into two categories according to their antioxidative capacity. Seven amino acids, including tryptophan, methionine, histidine, lysine, cysteine, arginine and tyrosine, were greater in total antioxidative capacity compared with the other 13 amino acids. Full article
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Open AccessArticle A Novel Strategy for Quantitative Analysis of Major Ginsenosides in Panacis Japonici Rhizoma with a Standardized Reference Fraction
Molecules 2017, 22(12), 2067; doi:10.3390/molecules22122067
Received: 1 November 2017 / Revised: 16 November 2017 / Accepted: 23 November 2017 / Published: 27 November 2017
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Abstract
Panacis Japonici Rhizoma (Zhu-Jie-Shen in Chinese), the root of P. japonicus C.A. Mey., is commonly used in traditional Chinese Medicine. Saponins are the major bioactive compounds in this herb. The similarity of polarity and structure of the natural products in herb caused the
[...] Read more.
Panacis Japonici Rhizoma (Zhu-Jie-Shen in Chinese), the root of P. japonicus C.A. Mey., is commonly used in traditional Chinese Medicine. Saponins are the major bioactive compounds in this herb. The similarity of polarity and structure of the natural products in herb caused the difficulty of purification and resulted in the shortage and high cost of the reference compounds, which has greatly hindered efforts toward quantification in quality control. A novel strategy using a standardized reference fraction for qualification of the major saponins in Panacis Japonici Rhizoma was proposed to easily and effectively control the quality of PJR. The strategy is feasible and reliable, and the methodology of the developed approach is also validated. The standardized reference fraction was used for quantification, which might solve the shortage of the pure reference compounds in the quality control of herbal medicines. Full article
(This article belongs to the Special Issue Current Trends in Ginseng Research)
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Open AccessArticle Live Fluorescent Staining Platform for Drug-Screening and Mechanism-Analysis in Zebrafish for Bone Mineralization
Molecules 2017, 22(12), 2068; doi:10.3390/molecules22122068
Received: 13 September 2017 / Revised: 10 November 2017 / Accepted: 22 November 2017 / Published: 27 November 2017
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Abstract
Currently, drug screening relies on cell-based experiments or on animal models to confirm biological effects. The mammalian system is considered too time-consuming, expensive and complex to perform high-throughput drug screening. There is a gap between in vitro cell-based models and the in vivo
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Currently, drug screening relies on cell-based experiments or on animal models to confirm biological effects. The mammalian system is considered too time-consuming, expensive and complex to perform high-throughput drug screening. There is a gap between in vitro cell-based models and the in vivo mammalian models. The zebrafish is an ideal model that could link preclinical toxicity screening with the drug development pipeline. Taking advantage of a highly conservative genomic, rapid development, large number of offspring, low cost and easy manipulation, zebrafish has been considered an excellent animal model for disease-based drug screening. In this study, zebrafish embryos were incubated with small molecular compounds that potentially affected bone mineralization in microplates. Two compounds of alendronate and dorsomorphin were used as positive and negative controls, respectively. The level of osteogenic mineralization was measured and quantified by using ImageJ software with fluorescent calcein-staining images. Among twenty-four tested compounds from the kinase inhibitor library, we identified two compounds, pentamidine and BML-267, which showed increased embryonic mineralization; while six compounds, RWJ-60475, levamisole HCL, tetramisole HCL, fenvalerate, NSC-663284, and BML-267ester, were inhibitory to bone mineralization. In addition, real time quantitative PCR (RT-qPCR) was performed to evaluate the biological pathways involved in bone metabolism at the molecular level. We confirmed that alendronate enhanced the level of bone mineralization by inhibiting osteoclast-related genes. In summary, our research established a simple method to screen potential bone metabolic drugs and to perform mechanism analysis for bone mineralization in vivo. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Coumarin Derivatives Solvent-Free Synthesis under Microwave Irradiation over Heterogeneous Solid Catalysts
Molecules 2017, 22(12), 2072; doi:10.3390/molecules22122072
Received: 31 October 2017 / Revised: 15 November 2017 / Accepted: 23 November 2017 / Published: 28 November 2017
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Abstract
A suitable methodology of synthesis of coumarin derivatives by Pechmann reaction over heterogeneous solid acid catalysts in a free solvent media under microwave irradiation is described. Resorcinol, phenol and ethyl acetoacetate were selected as model reactants in the Pechmann condensation. The catalytic activity
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A suitable methodology of synthesis of coumarin derivatives by Pechmann reaction over heterogeneous solid acid catalysts in a free solvent media under microwave irradiation is described. Resorcinol, phenol and ethyl acetoacetate were selected as model reactants in the Pechmann condensation. The catalytic activity of several materials—Amberlyst-15, zeolite β and sulfonic acid functionalized hybrid silica—in solvent-free microwave-assisted synthesis of the corresponding coumarin derivatives has been investigated in detail. 7-Hydroxy-4-methylcoumarin and 4-methylcoumarin were obtained in 97% and 43% yields, respectively, over Amberlyst-15. This was the most active catalyst in the Pechmann reaction under studied conditions. Full article
(This article belongs to the Special Issue Meeting of the Spanish Catalysis Society (SECAT’17))
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Open AccessArticle Metabolites Produced by an Endophytic Phomopsis sp. and Their Anti-TMV Activity
Molecules 2017, 22(12), 2073; doi:10.3390/molecules22122073
Received: 19 September 2017 / Revised: 8 November 2017 / Accepted: 25 November 2017 / Published: 27 November 2017
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Abstract
The fermentation and isolation of metabolites produced by an endophytic fungus, which was identified as Phomopsis sp. FJBR-11, based on phylogenetic analysis, led to the identification of six compounds, including dothiorelones A–C, and H, and cytosporones C and U. Among these compounds, cytosporone
[...] Read more.
The fermentation and isolation of metabolites produced by an endophytic fungus, which was identified as Phomopsis sp. FJBR-11, based on phylogenetic analysis, led to the identification of six compounds, including dothiorelones A–C, and H, and cytosporones C and U. Among these compounds, cytosporone U exhibited potent inhibitory activity against Tobacco mosaic virus (TMV). Moreover, the crude and a purified exopolysaccharide were proved to possess strong inhibitory effects against the virus infection. Full article
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Open AccessArticle One-Step Carbon Coating and Polyacrylamide Functionalization of Fe3O4 Nanoparticles for Enhancing Magnetic Adsorptive-Remediation of Heavy Metals
Molecules 2017, 22(12), 2074; doi:10.3390/molecules22122074
Received: 26 October 2017 / Revised: 21 November 2017 / Accepted: 23 November 2017 / Published: 27 November 2017
PDF Full-text (3513 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Magnetic nanoparticles are used in adsorptive removal of heavy metals from polluted wastewater. However, their poor stability in an acidic medium necessitates their protection with a coating layer. Coating magnetic nanoparticles with carbon showed proper protection but the heavy metal removal efficiency was
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Magnetic nanoparticles are used in adsorptive removal of heavy metals from polluted wastewater. However, their poor stability in an acidic medium necessitates their protection with a coating layer. Coating magnetic nanoparticles with carbon showed proper protection but the heavy metal removal efficiency was slightly weak. However, to boost the removal efficiencies of surface functionalization, polyacrylamide was applied to carbon-coated Fe3O4 nanoparticles. In this paper, to facilitate the synthesis process, one-step carbon coating and polyacrylamide functionalization were conducted using the hydrothermal technique with the aim of enhancing the adsorptive removal capacity of Fe3O4 nanoparticles towards some heavy metals such as Cu(II), Ni(II), Co(II), and Cd(II). The results showed that the one-step process succeeded in developing a carbon coating layer and polyacrylamide functionality on Fe3O4 nanoparticles. The stability of the magnetic Fe3O4 nanoparticles as an adsorbent in an acidic medium was improved due to its resistance to the dissolution that was gained during carbon coating and surface functionalization with polyacrylamide. The adsorptive removal process was investigated in relation to various parameters such as pH, time of contact, metal ion concentrations, adsorbent dose, and temperature. The polyacrylamide functionalized Fe3O4 showed an improvement in the adsorption capacity as compared with the unfunctionalized one. The conditions for superior adsorption were obtained at pH 6; time of contact, 90 min; metal solution concentration, 200 mg/L; adsorbent dose, 0.3 g/L. The modeling of the adsorption data was found to be consistent with the pseudo-second-order kinetic model, which suggests a fast adsorption process. However, the equilibrium data modeling was consistent with both the Langmuir and Freundlich isotherms. Furthermore, the thermodynamic parameters of the adsorptive removal process, including ΔG°, ΔH°, and ΔS°, indicated a spontaneous and endothermic sorption process. The developed adsorbent can be utilized further for industrial-based applications. Full article
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Open AccessArticle The Design and Evaluation of an l-Dopa–Lazabemide Prodrug for the Treatment of Parkinson’s Disease
Molecules 2017, 22(12), 2076; doi:10.3390/molecules22122076
Received: 5 October 2017 / Revised: 22 November 2017 / Accepted: 23 November 2017 / Published: 27 November 2017
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Abstract
l-Dopa, the metabolic precursor of dopamine, is the treatment of choice for the symptomatic relief of the advanced stages of Parkinson’s disease. The oral bioavailability of l-dopa, however, is only about 10% to 30%, and less than 1% of the oral dose is
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l-Dopa, the metabolic precursor of dopamine, is the treatment of choice for the symptomatic relief of the advanced stages of Parkinson’s disease. The oral bioavailability of l-dopa, however, is only about 10% to 30%, and less than 1% of the oral dose is estimated to reach the brain unchanged. l-Dopa’s physicochemical properties are responsible for its poor bioavailability, short half-life and the wide range of inter- and intrapatient variations of plasma levels. An l-dopa–lazabemide prodrug is proposed to overcome the problems associated with l-dopa absorption. Lazabemide is a monoamine oxidase (MAO)-B inhibitor, a class of compounds that slows the depletion of dopamine stores in Parkinson’s disease and elevates dopamine levels produced by exogenously administered l-dopa. l-Dopa was linked at the carboxylate with the primary aminyl functional group of lazabemide via an amide, a strategy which is anticipated to protect l-dopa against peripheral decarboxylation and possibly also enhance the membrane permeability of the prodrug. Selected physicochemical and biochemical properties of the prodrug were determined and included lipophilicity (logD), solubility, passive diffusion permeability, pKa, chemical and metabolic stability as well as cytotoxicity. Although oral and i.p. treatment of mice with the prodrug did not result in enhanced striatal dopamine levels, 3,4-dihydroxyphenylacetic acid (DOPAC) levels were significantly depressed compared to saline, l-dopa and carbidopa/l-dopa treatment. Based on the results, further preclinical evaluation of the l-dopa–lazabemide prodrug should be undertaken with the aim of discovering prodrugs that may be advanced to the clinical stages of development. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3β/β-Catenin Signaling Pathways
Molecules 2017, 22(12), 2077; doi:10.3390/molecules22122077
Received: 2 November 2017 / Revised: 22 November 2017 / Accepted: 24 November 2017 / Published: 28 November 2017
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Abstract
Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds,
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Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one (PMPP) was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study. Further investigations revealed that Akt and GSK3β were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents. Full article
(This article belongs to the Section Chemical Biology)
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Open AccessArticle Alcohol Interactions with Lipid Bilayers
Molecules 2017, 22(12), 2078; doi:10.3390/molecules22122078
Received: 3 November 2017 / Revised: 23 November 2017 / Accepted: 24 November 2017 / Published: 28 November 2017
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Abstract
We investigate the structural changes to lipid membrane that ensue from the addition of aliphatic alcohols with various alkyl tail lengths. Small angle neutron diffraction from flat lipid bilayers that are hydrated through water vapor has been employed to eliminate possible artefacts of
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We investigate the structural changes to lipid membrane that ensue from the addition of aliphatic alcohols with various alkyl tail lengths. Small angle neutron diffraction from flat lipid bilayers that are hydrated through water vapor has been employed to eliminate possible artefacts of the membrane curvature and the alcohol’s membrane-water partitioning. We have observed clear changes to membrane structure in both transversal and lateral directions. Most importantly, our results suggest the alteration of the membrane-water interface. The water encroachment has shifted in the way that alcohol loaded bilayers absorbed more water molecules when compared to the neat lipid bilayers. The experimental results have been corroborated by molecular dynamics simulations to reveal further details. Namely, the order parameter profiles have been fruitful in correlating the mechanical model of structural changes to the effect of anesthesia. Full article
(This article belongs to the Special Issue Phospholipids: Structure and Function)
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Open AccessArticle Identification of DNA–protein Binding Sites through Multi-Scale Local Average Blocks on Sequence Information
Molecules 2017, 22(12), 2079; doi:10.3390/molecules22122079
Received: 31 October 2017 / Revised: 22 November 2017 / Accepted: 24 November 2017 / Published: 28 November 2017
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Abstract
DNA–protein interactions appear as pivotal roles in diverse biological procedures and are paramount for cell metabolism, while identifying them with computational means is a kind of prudent scenario in depleting in vitro and in vivo experimental charging. A variety of state-of-the-art investigations have
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DNA–protein interactions appear as pivotal roles in diverse biological procedures and are paramount for cell metabolism, while identifying them with computational means is a kind of prudent scenario in depleting in vitro and in vivo experimental charging. A variety of state-of-the-art investigations have been elucidated to improve the accuracy of the DNA–protein binding sites prediction. Nevertheless, structure-based approaches are limited under the condition without 3D information, and the predictive validity is still refinable. In this essay, we address a kind of competitive method called Multi-scale Local Average Blocks (MLAB) algorithm to solve this issue. Different from structure-based routes, MLAB exploits a strategy that not only extracts local evolutionary information from primary sequences, but also using predicts solvent accessibility. Moreover, the construction about predictors of DNA–protein binding sites wields an ensemble weighted sparse representation model with random under-sampling. To evaluate the performance of MLAB, we conduct comprehensive experiments of DNA–protein binding sites prediction. MLAB gives M C C of 0.392 , 0.315 , 0.439 and 0.245 on PDNA-543, PDNA-41, PDNA-316 and PDNA-52 datasets, respectively. It shows that MLAB gains advantages by comparing with other outstanding methods. M C C for our method is increased by at least 0.053 , 0.015 and 0.064 on PDNA-543, PDNA-41 and PDNA-316 datasets, respectively. Full article
(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)
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Open AccessFeature PaperArticle Fluorinated Analogs of Organosulfur Compounds from Garlic (Allium sativum): Synthesis, Chemistry and Anti-Angiogenesis and Antithrombotic Studies
Molecules 2017, 22(12), 2081; doi:10.3390/molecules22122081
Received: 6 October 2017 / Accepted: 24 November 2017 / Published: 28 November 2017
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Abstract
We describe the synthesis, reactivity, and antithrombotic and anti-angiogenesis activity of difluoroallicin (S-(2-fluoroallyl) 2-fluoroprop-2-ene-1-sulfinothioate) and S-2-fluoro-2-propenyl-l-cysteine, both easily prepared from commercially available 3-chloro-2-fluoroprop-1-ene, as well as the synthesis of 1,2-bis(2-fluoroallyl)disulfane, 5-fluoro-3-(1-fluorovinyl)-3,4-dihydro-1,2-dithiin, trifluoroajoene ((E,Z)-1-(2-fluoro-3-((2-fluoroallyl)sulfinyl)prop-1-en-1-yl)-2-(2-fluoroallyl)disulfane), and
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We describe the synthesis, reactivity, and antithrombotic and anti-angiogenesis activity of difluoroallicin (S-(2-fluoroallyl) 2-fluoroprop-2-ene-1-sulfinothioate) and S-2-fluoro-2-propenyl-l-cysteine, both easily prepared from commercially available 3-chloro-2-fluoroprop-1-ene, as well as the synthesis of 1,2-bis(2-fluoroallyl)disulfane, 5-fluoro-3-(1-fluorovinyl)-3,4-dihydro-1,2-dithiin, trifluoroajoene ((E,Z)-1-(2-fluoro-3-((2-fluoroallyl)sulfinyl)prop-1-en-1-yl)-2-(2-fluoroallyl)disulfane), and a bis(2-fluoroallyl)polysulfane mixture. All tested organosulfur compounds demonstrated effective inhibition of either FGF or VEG-mediated angiogenesis (anti-angiogenesis activity) in the chick chorioallantoic membrane (CAM) or the mouse Matrigel® models. No embryo mortality was observed. Difluoroallicin demonstrated greater inhibition (p < 0.01) versus organosulfur compounds tested. Difluoroallicin demonstrated dose-dependent inhibition of angiogenesis in the mouse Matrigel® model, with maximal inhibition at 0.01 mg/implant. Allicin and difluoroallicin showed an effective antiplatelet effect in suppressing platelet aggregation compared to other organosulfur compounds tested. In platelet/fibrin clotting (anti-coagulant activity), difluoroallicin showed concentration-dependent inhibition of clot strength compared to allicin and the other organosulfur compounds tested. Full article
(This article belongs to the Special Issue The Chemistry of Alliums)
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Open AccessArticle trans-Double Bond-Containing Liposomes as Potential Carriers for Drug Delivery
Molecules 2017, 22(12), 2082; doi:10.3390/molecules22122082
Received: 29 October 2017 / Accepted: 25 November 2017 / Published: 28 November 2017
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Abstract
The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural
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The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry. Here we report on the effects of the addition of trans-phospholipids supplied in different amounts to other liposome constituents (cholesterol, neutral phospholipids and cationic surfactants), on the size, ζ-potential and stability of liposomal formulations and on their ability to encapsulate two dyes such as rhodamine B and fluorescein. From a biotechnological point of view, trans-containing liposomes proved to have different characteristics from those containing the cis analogues, and to influence the incorporation and release of the dyes. These results open new perspectives in the use of the unnatural lipid geometry, for the purpose of changing liposome behavior and/or of obtaining molecular interferences, also in view of synergic effects of cell toxicity, especially in antitumoral strategies. Full article
(This article belongs to the Special Issue Phospholipids: Structure and Function)
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Open AccessArticle Design, Synthesis, and Fungicidal Activity of Novel Thiosemicarbazide Derivatives Containing Piperidine Fragments
Molecules 2017, 22(12), 2085; doi:10.3390/molecules22122085
Received: 6 November 2017 / Revised: 23 November 2017 / Accepted: 27 November 2017 / Published: 11 December 2017
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Abstract
In order to discover novel eco-friendly lead compounds for plant pathogenic fungi control, a series of benzaldehyde thiosemicarbazide derivatives with a piperidine moiety have been designed and synthesized. Fungicidal activities of all the synthesized compounds were evaluated in vitro. The results indicated that
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In order to discover novel eco-friendly lead compounds for plant pathogenic fungi control, a series of benzaldehyde thiosemicarbazide derivatives with a piperidine moiety have been designed and synthesized. Fungicidal activities of all the synthesized compounds were evaluated in vitro. The results indicated that all the title compounds exhibited moderate to good fungicidal activities. Compound 3b displayed excellent activities against Pythium aphanidermatum, Rhizoctonia solani, Valsa mali, and Gaeu-mannomyces graminsis, with EC50 values lower than 10 μg/mL. Especially, in the case of Pythium aphanidermatum, its activity (EC50 = 1.6 μg/mL) is superior to the commercial azoxystrobin (EC50 = 16.9 μg/mL) and close to fluopicolide (EC50 = 1.0 μg/mL). Initial structure–activity relationship (SAR) analysis showed that the heterocyclic piperidine group can influence the biological activities of the title compounds significantly. The fungicidal activity of compounds with piperidine is better than that of compounds without piperidine. The highly-active compound 3b, with its simple structure and easy synthetic route, is worthy to be further studied as a new lead fungicide. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessArticle Cancer Classification Based on Support Vector Machine Optimized by Particle Swarm Optimization and Artificial Bee Colony
Molecules 2017, 22(12), 2086; doi:10.3390/molecules22122086
Received: 27 October 2017 / Accepted: 23 November 2017 / Published: 29 November 2017
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Abstract
Intelligent optimization algorithms have advantages in dealing with complex nonlinear problems accompanied by good flexibility and adaptability. In this paper, the FCBF (Fast Correlation-Based Feature selection) method is used to filter irrelevant and redundant features in order to improve the quality of cancer
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Intelligent optimization algorithms have advantages in dealing with complex nonlinear problems accompanied by good flexibility and adaptability. In this paper, the FCBF (Fast Correlation-Based Feature selection) method is used to filter irrelevant and redundant features in order to improve the quality of cancer classification. Then, we perform classification based on SVM (Support Vector Machine) optimized by PSO (Particle Swarm Optimization) combined with ABC (Artificial Bee Colony) approaches, which is represented as PA-SVM. The proposed PA-SVM method is applied to nine cancer datasets, including five datasets of outcome prediction and a protein dataset of ovarian cancer. By comparison with other classification methods, the results demonstrate the effectiveness and the robustness of the proposed PA-SVM method in handling various types of data for cancer classification. Full article
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Open AccessArticle Enhanced Intestinal Permeability of Bufalin by a Novel Bufalin-Peptide-Dendrimer Inclusion through Caco-2 Cell Monolayer
Molecules 2017, 22(12), 2088; doi:10.3390/molecules22122088
Received: 29 October 2017 / Revised: 17 November 2017 / Accepted: 23 November 2017 / Published: 29 November 2017
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Abstract
Bufalin (BFL) has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a
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Bufalin (BFL) has excellent physiological activities such as defending tumors, improving cardiac function, and so on. However, due to its poor water-solubility and bioavailability, the clinical application of BFL remains limited. In order to improve bioavailability of BFL, in our previous research, a novel peptide-dendrimer (PD) was synthesized and applied to encapsulate BFL. In the present study, we investigate the absorption property and mechanism of BFL in free form and BFL-peptide-dendrimer inclusion (BPDI) delivery system by using the Caco-2 cell monolayer model in vitro. The apparent permeability coefficient (Papp) values of BFL in free or BPDI form were over 1.0 × 10−6 cm/s. Meanwhile, their almost equal bi-directional transport and linear transport percentage with time and concentration course indicated that BFL in both forms was absorbed mainly through passive diffusion. The most important result is that the Papp values of BFL increased about three-fold more BPDI than those of its free form, which indicated the intestinal permeability of BFL could be improved while BFL was encapsulated in BPDI form. Therefore, PD encapsulation may be a potential delivery system to increase the bioavailability of BFL. Full article
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Open AccessArticle HPLC-PDA-MS/MS Characterization of Bioactive Secondary Metabolites from Turraea fischeri Bark Extract and Its Antioxidant and Hepatoprotective Activities In Vivo
Molecules 2017, 22(12), 2089; doi:10.3390/molecules22122089
Received: 6 November 2017 / Revised: 21 November 2017 / Accepted: 27 November 2017 / Published: 29 November 2017
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Abstract
Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the
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Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D-galactosamine when compared with rats treated with D-galactosamine alone. In conclusion, T. fischeri is apromising candidate for health-promoting and for pharmaceutical applications. Full article
(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)
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Open AccessFeature PaperArticle 2-Substituted Aniline as a Simple Scaffold for LuxR-Regulated QS Modulation
Molecules 2017, 22(12), 2090; doi:10.3390/molecules22122090
Received: 29 September 2017 / Revised: 17 November 2017 / Accepted: 27 November 2017 / Published: 29 November 2017
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Abstract
The ability of the 2-substituted aniline motif to serve as a scaffold for designing potential LuxR-regulated quorum sensing (QS) modulators has been investigated, using docking experiments and biological evaluation of a series of 15 specially synthesized compounds. Aniline, 2-acetyl-aniline and 2-nitroaniline were considered,
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The ability of the 2-substituted aniline motif to serve as a scaffold for designing potential LuxR-regulated quorum sensing (QS) modulators has been investigated, using docking experiments and biological evaluation of a series of 15 specially synthesized compounds. Aniline, 2-acetyl-aniline and 2-nitroaniline were considered, as well as their N-acylated derivatives. Docking experiments showed that the 2-substituted aniline motif fits within the LuxR binding site at the place of the lactone moiety of AHL, and the biological evaluation revealed QS antagonisitic activity for several compounds, validating the hypothesis that this scaffold acts on QS. Structure activity relationships are discussed regarding interactions with the key residues of the LuxR binding site, showing significant variations in the H-bonding pattern. Full article
(This article belongs to the Special Issue Design and Synthesis of Quorum-Sensing Inhibitors)
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Open AccessArticle Biological Properties of Low-Toxicity PLGA and PLGA/PHB Fibrous Nanocomposite Implants for Osseous Tissue Regeneration. Part I: Evaluation of Potential Biotoxicity
Molecules 2017, 22(12), 2092; doi:10.3390/molecules22122092
Received: 24 October 2017 / Revised: 17 November 2017 / Accepted: 27 November 2017 / Published: 29 November 2017
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Abstract
In response to the demand for new implant materials characterized by high biocompatibility and bioresorption, two prototypes of fibrous nanocomposite implants for osseous tissue regeneration made of a newly developed blend of poly(l-lactide-co-glycolide) (PLGA) and syntheticpoly([R,S]-3-hydroxybutyrate), PLGA/PHB,
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In response to the demand for new implant materials characterized by high biocompatibility and bioresorption, two prototypes of fibrous nanocomposite implants for osseous tissue regeneration made of a newly developed blend of poly(l-lactide-co-glycolide) (PLGA) and syntheticpoly([R,S]-3-hydroxybutyrate), PLGA/PHB, have been developed and fabricated. Afibre-forming copolymer of glycolide and l-lactide (PLGA) was obtained by a unique method of synthesis carried out in blocksusing Zr(AcAc)4 as an initiator. The prototypes of the implants are composed of three layers of PLGA or PLGA/PHB, nonwoven fabrics with a pore structure designed to provide the best conditions for the cell proliferation. The bioactivity of the proposed implants has been imparted by introducing a hydroxyapatite material and IGF1, a growth factor. The developed prototypes of implants have been subjected to a set of in vitro and in vivobiocompatibility tests: in vitro cytotoxic effect, in vitro genotoxicity and systemic toxicity. Rabbitsshowed no signs of negative reactionafter implantation of the experimental implant prototypes. Full article
(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)
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Open AccessArticle Evaluation of Inulin Replacing Chitosan in a Polyurethane/Polysaccharide Material for Pb2+ Removal
Molecules 2017, 22(12), 2093; doi:10.3390/molecules22122093
Received: 26 October 2017 / Revised: 26 November 2017 / Accepted: 27 November 2017 / Published: 29 November 2017
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Abstract
Downstream waste from industry and other industrial processes could increase concentration of heavy metals in water. These pollutants are commonly removed by adsorption because it is an effective and economical method. Previously, we reported adsorption capacity of a chitosan/polyurethane/titanium dioxide (TiO2)
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Downstream waste from industry and other industrial processes could increase concentration of heavy metals in water. These pollutants are commonly removed by adsorption because it is an effective and economical method. Previously, we reported adsorption capacity of a chitosan/polyurethane/titanium dioxide (TiO2) composite for three ions in a dynamic wastewater system. There, increasing the chitosan concentration in composite increased the cation removal as well; however, for ratios higher than 50% of chitosan/TiO2, the manufacturing cost increased significantly. In this work, we address the manufacturing cost problem by proposing a new formulation of the composite. Our hypothesis is that inulin could replace chitosan in the composite formulation, either wholly or in part. In this exploratory research, three blends were prepared with a polyurethane matrix using inulin or/and chitosan. Adsorption was evaluated using a colorimetric method and the Langmuir and Freundlich models. Fourier-transform infrared spectroscopy (FTIR) spectra, scanning electron microscopy (SEM) micrographs, differential scanning calorimetry and thermogravimetric analysis curves were obtained to characterize blends. Results indicate that blends are suitable for toxic materials removal (specifically lead II, Pb2+). Material characterization indicates that polysaccharides were distributed in polyurethane’s external part, thus improving adsorption. Thermal degradation of materials was found above 200 °C. Comparing the blends data, inulin could replace chitosan in part and thereby improve the cost efficiency and scalability of the production process of the polyurethane based-adsorbent. Further research with different inulin/chitosan ratios in the adsorbent and experiments with a dynamic system are justified. Full article
(This article belongs to the Special Issue Polysaccharide-based Materials)
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Open AccessArticle The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)
Molecules 2017, 22(12), 2094; doi:10.3390/molecules22122094
Received: 27 October 2017 / Accepted: 24 November 2017 / Published: 29 November 2017
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Abstract
Proteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host’s immune system that allows long-term
[...] Read more.
Proteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host’s immune system that allows long-term persistence of the parasites. So far, only a limited number of PC-modified proteins, mainly from nematodes, have been identified. Infections caused by Leishmania spp. (e.g., L. infantum in southern Europe) affect about 12 million people worldwide and are characterized by a wide spectrum of clinical forms in humans, ranging from cutaneous to fatal visceral leishmaniasis. To establish and maintain the infection, these protozoa are dependent on the secretion of effector molecules into the host for modulating their immune system. In this project, we analyzed the PC modification of L. infantum promastigotes by 2D-gel based proteomics. Western blot analysis with the PC-specific antibody TEPC-15 revealed one PC-substituted protein in this organism, identified as eEF1α. We could demonstrate that the binding of eEF1α to one of its downstream effectors is dependent on its PC-modification. In this study we provide evidence that in this parasite the modification of eEF1α with PC may be essential for its function as an important virulence factor. Full article
(This article belongs to the Special Issue Protein Modifications and Bioconjugation)
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Open AccessArticle Anti-Candida Activity of Bursera morelensis Ramirez Essential Oil and Two Compounds, α-Pinene and γ-Terpinene—An In Vitro Study
Molecules 2017, 22(12), 2095; doi:10.3390/molecules22122095
Received: 2 November 2017 / Revised: 25 November 2017 / Accepted: 27 November 2017 / Published: 5 December 2017
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Abstract
The candidiasis caused by C. albicans is a public health problem. The abuse of antifungals has contributed to the development of resistance. B. morelensis has demonstrated antibacterial and antifungal activities. In this work the activity of the essential oil of B. morelensis was
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The candidiasis caused by C. albicans is a public health problem. The abuse of antifungals has contributed to the development of resistance. B. morelensis has demonstrated antibacterial and antifungal activities. In this work the activity of the essential oil of B. morelensis was evaluated and for its two pure compounds with analysis of the different mechanisms of pathogenesis important for C. albicans. The essential oil was obtained by the hydro-distillation method and analyzed using GC–MS. The anti-Candida activity was compared between to essential oil, α-Pinene and γ-Terpinene. GC–MS of the essential oil demonstrated the presence of 13 compounds. The essential oil showed antifungal activity against four C. albicans strains. The most sensitive strain was C. albicans 14065 (MFC 2.0 mg/mL and MIC50 0.125 mg/mL) with α-Pinene and γ-Terpinene having MFCs of 4.0 and 16.0 mg/mL respectively. The essential oil inhibited the growth of the germ tube in 87.94% (8.0 mg/mL). Furthermore, it was observed that the essential oil diminishes the transcription of the gene INT1. This work provides evidence that confirms the anti-Candida activity of the B. morelensis essential oil and its effect on the growth of the germ tube and transcription of the gene INT1. Full article
(This article belongs to the Special Issue Essential Oils as Antimicrobial and Anti-infectious Agents)
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Open AccessArticle In Vivo Activity of LCB 01-0699, a Prodrug of LCB 01-0648, against Staphylococcus aureus
Molecules 2017, 22(12), 2096; doi:10.3390/molecules22122096
Received: 10 November 2017 / Revised: 23 November 2017 / Accepted: 28 November 2017 / Published: 29 November 2017
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Abstract
LCB01-0648 is a novel oxazolidinone compound that shows potent antibacterial activities against most Gram-positive cocci, including the multi-drug resistant Staphylococcus aureus. In this study, in vivo activity of LCB01-0699, a LCB01-0648 prodrug, against S. aureus was evaluated in comparison with that
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LCB01-0648 is a novel oxazolidinone compound that shows potent antibacterial activities against most Gram-positive cocci, including the multi-drug resistant Staphylococcus aureus. In this study, in vivo activity of LCB01-0699, a LCB01-0648 prodrug, against S. aureus was evaluated in comparison with that of Linezolid. The results of the systemic infection study demonstrated that LCB01-0699 was more potent than Linezolid against methicillin-susceptible and -resistant S. aureus strains. The in vivo efficacy of LCB01-0699 against methicillin-susceptible and -resistant S. aureus strains in a skin infection model showed more potent activity than Linezolid. LCB01-0699 shows potent in vivo activity against methicillin-susceptible and -resistant S. aureus strains, suggesting that LCB01-0699 would be a novel candidate for the treatment of these infectious diseases caused by S. aureus. Full article
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Open AccessArticle Platinum-Catalyzed Allylation of 2,3-Disubstituted Indoles with Allylic Acetates
Molecules 2017, 22(12), 2097; doi:10.3390/molecules22122097
Received: 20 October 2017 / Revised: 24 November 2017 / Accepted: 28 November 2017 / Published: 29 November 2017
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Abstract
Given the importance of heterocycle indole derivatives, much effort has been directed toward the development of methods for functionalization of the indole nucleus at N1 and C3 sites. Moreover, the platinum-catalyzed allyation of nucleophiles was an established and efficient way, which has been
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Given the importance of heterocycle indole derivatives, much effort has been directed toward the development of methods for functionalization of the indole nucleus at N1 and C3 sites. Moreover, the platinum-catalyzed allyation of nucleophiles was an established and efficient way, which has been applied to medicinal and organic chemistry. In our research, the platinum-catalyzed 2,3-disubstitued indoles with allylic acetates was investigated under different conditions. Herein, we established a simple, convenient, and efficient method, which afforded high yield of allylated indoles. Full article
(This article belongs to the Special Issue Organometallic Catalysis in Organic Synthesis)
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Open AccessFeature PaperArticle Comparison of the Binding of Reversible Inhibitors to Human Butyrylcholinesterase and Acetylcholinesterase: A Crystallographic, Kinetic and Calorimetric Study
Molecules 2017, 22(12), 2098; doi:10.3390/molecules22122098
Received: 26 October 2017 / Revised: 26 November 2017 / Accepted: 27 November 2017 / Published: 29 November 2017
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Abstract
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. Although closely related, these enzymes display very different substrate specificities that only partially overlap. This disparity is largely due to differences in the number of aromatic
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Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. Although closely related, these enzymes display very different substrate specificities that only partially overlap. This disparity is largely due to differences in the number of aromatic residues lining the active site gorge, which leads to large differences in the shape of the gorge and potentially to distinct interactions with an individual ligand. Considerable structural information is available for the binding of a wide diversity of ligands to AChE. In contrast, structural data on the binding of reversible ligands to BChE are lacking. In a recent effort, an inhibitor competition approach was used to probe the overlap of ligand binding sites in BChE. Here, we extend this study by solving the crystal structures of human BChE in complex with five reversible ligands, namely, decamethonium, thioflavin T, propidium, huprine, and ethopropazine. We compare these structures to equivalent AChE complexes when available in the protein data bank and supplement this comparison with kinetic data and observations from isothermal titration calorimetry. This new information now allows us to define the binding mode of various ligand families and will be of importance in designing specific reversible ligands of BChE that behave as inhibitors or reactivators. Full article
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Open AccessArticle Heterogenization of Ketone Catalyst for Epoxidation by Low Pressure Plasma Fluorination of Silica Gel Supports
Molecules 2017, 22(12), 2099; doi:10.3390/molecules22122099
Received: 1 November 2017 / Revised: 22 November 2017 / Accepted: 27 November 2017 / Published: 30 November 2017
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Abstract
Low pressure plasma was used for preparing heterogeneous organocatalysts 2-(A)-(C) suitable for dioxirane-mediated epoxidations. Heterogenization was accomplished by adsorption of the methyl perfluoroheptyl ketone (2) on fluorinated supports (A)-(C) deriving from the
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Low pressure plasma was used for preparing heterogeneous organocatalysts 2-(A)-(C) suitable for dioxirane-mediated epoxidations. Heterogenization was accomplished by adsorption of the methyl perfluoroheptyl ketone (2) on fluorinated supports (A)-(C) deriving from the treatment of commercial C8-silica gel in low pressure plasma fed with fluorocarbons. Catalyst 2-(C) proved to be the most efficient one, promoting epoxidation of an array of alkenes, including unsaturated fatty esters like methyl oleate (10) and the triglyceride soybean oil (11), with the cheap potassium peroxymonosulfate KHSO5 (caroate) as a green oxidant. Notably, the perfluorinated matrix gives rise to the activation of caroate, generating singlet oxygen. Materials were characterized by infrared Attenuated Total Reflectance spectroscopy (ATR-FTIR), X-ray Photoelectron Spectroscopy (XPS ) and Emission Scanning Electron Microscope (FESEM). Full article
(This article belongs to the Special Issue Chemical Transformation of Renewable Material for Green Chemistry)
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Open AccessArticle Synthesis and In Vitro Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain
Molecules 2017, 22(12), 2100; doi:10.3390/molecules22122100
Received: 30 October 2017 / Revised: 20 November 2017 / Accepted: 27 November 2017 / Published: 30 November 2017
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Abstract
Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8ah) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water
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Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8ah) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log kw values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor k (log k) and volume fraction of a mobile phase modifier (ϕM), varied from 2.113 (compound 8e) to 2.930 (8h) and indicated relatively high lipophilicity of these salts. Electronic properties of the molecules 8ah were investigated by evaluation of their UV/Vis spectra. In a next phase of the research, the compounds 8ah were in vitro screened against M. tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794), M. kansasii CNCTC My 235/80 (identical with ATCC 12478), a M. kansasii 6 509/96 clinical isolate, M. avium CNCTC My 330/80 (identical with ATCC 25291) and M. avium intracellulare ATCC 13950, respectively, as well as against M. kansasii CIT11/06, M. avium subsp. paratuberculosis CIT03 and M. avium hominissuis CIT10/08 clinical isolates using isoniazid, ethambutol, ofloxacin, ciprofloxacin or pyrazinamide as reference drugs. The tested compounds 8ah were found to be the most promising against M. tuberculosis; a MIC = 8 μM was observed for the most effective 1-(2-{4-[(butoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)piperazin-1-ium chloride (8h). In addition, all of them showed low (insignificant) in vitro toxicity against a human monocytic leukemia THP-1 cell line, as observed LD50 values > 30 μM indicated. The structure–antimycobacterial activity relationships of the analyzed 8ah series are also discussed. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessArticle The Antitumor Constituents from Hedyotis Diffusa Willd
Molecules 2017, 22(12), 2101; doi:10.3390/molecules22122101
Received: 4 November 2017 / Revised: 18 November 2017 / Accepted: 27 November 2017 / Published: 30 November 2017
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Abstract
As a TCM, Hedyotis diffusa Willd. has been using to treat malignant tumors, and many studies also showed that the extracts from Hedyotis diffusa Willd. possessed evident antitumor activities. Therefore, we carried out chemical study on Hedyotis diffusa Willd. and investigated the cytotoxicity
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As a TCM, Hedyotis diffusa Willd. has been using to treat malignant tumors, and many studies also showed that the extracts from Hedyotis diffusa Willd. possessed evident antitumor activities. Therefore, we carried out chemical study on Hedyotis diffusa Willd. and investigated the cytotoxicity of the obtained compounds on a panel of eight tumor cell lines. As a result, four new compounds were isolated from Hedyotis diffusa Willd., including three iridoid glycosides of Shecaoiridoidside A–C (13) and a cerebroside of shecaocerenoside A (4). Also, six known iridoid compounds (510) were also obtained. The cytotoxicity of all compounds against human tumor cell lines of HL-60, HeLa, HCT15, A459, HepG2, PC-3, CNE-2, and BCG-823 were also evaluated in vitro. New compound 3 exhibited evident cytotoxicity to all tumor cell lines except the Hela, and the IC50 values are from 9.6 µM to 62.2 µM, while new compound 4 showed moderate cytotoxicity to all the cell lines, and the IC50 values are from 33.6 µM to 89.3 µM. By contrast, new compound 1 and known compound 9 showed moderate cytotoxicity to HCT15, A459, and HepG2 selectively. Known compound 7 also exhibited moderate cytotoxicity to HCT15 and A459 selectively. Full article
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Open AccessArticle In Vivo and In Vitro Activities and ADME-Tox Profile of a Quinolizidine-Modified 4-Aminoquinoline: A Potent Anti-P. falciparum and Anti-P. vivax Blood-Stage Antimalarial
Molecules 2017, 22(12), 2102; doi:10.3390/molecules22122102
Received: 24 October 2017 / Revised: 20 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
Natural products are a prolific source for the identification of new biologically active compounds. In the present work, we studied the in vitro and in vivo antimalarial efficacy and ADME-Tox profile of a molecular hybrid (AM1) between 4-aminoquinoline and a quinolizidine moiety derived
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Natural products are a prolific source for the identification of new biologically active compounds. In the present work, we studied the in vitro and in vivo antimalarial efficacy and ADME-Tox profile of a molecular hybrid (AM1) between 4-aminoquinoline and a quinolizidine moiety derived from lupinine (Lupinus luteus). The aim was to find a compound endowed with the target product profile-1 (TCP-1: molecules that clear asexual blood-stage parasitaemia), proposed by the Medicine for Malaria Venture to accomplish the goal of malaria elimination/eradication. AM1 displayed a very attractive profile in terms of both in vitro and in vivo activity. By using standard in vitro antimalarial assays, AM1 showed low nanomolar inhibitory activity against chloroquine-sensitive and resistant P. falciparum strains (range IC50 16–53 nM), matched with a high potency against P. vivax field isolates (Mean IC50 29 nM). Low toxicity and additivity with artemisinin derivatives were also demonstrated in vitro. High in vivo oral efficacy was observed in both P. berghei and P. yoelii mouse models with IC50 values comparable or better than those of chloroquine. The metabolic stability in different species and the pharmacokinetic profile in the mouse model makes AM1 a compound worth further investigation as a potential novel schizonticidal agent. Full article
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Open AccessArticle Novel Artificial Tears Containing Cross-Linked Hyaluronic Acid: An In Vitro Re-Epithelialization Study
Molecules 2017, 22(12), 2104; doi:10.3390/molecules22122104
Received: 1 November 2017 / Accepted: 27 November 2017 / Published: 30 November 2017
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Abstract
Dry eye syndrome is a common disease which can damage the corneal epithelium. It is treated with eye drops to stimulate tear production and hydrate the corneal surface. The most prescribed artificial tear remedies contain hyaluronic acid (HA), which enhances epithelial wound healing,
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Dry eye syndrome is a common disease which can damage the corneal epithelium. It is treated with eye drops to stimulate tear production and hydrate the corneal surface. The most prescribed artificial tear remedies contain hyaluronic acid (HA), which enhances epithelial wound healing, improving tissue health. To the best of our knowledge, only a few recent studies have investigated cross-linked HA (HA-CL) in eye drops for human applications. This work consists in an in vitro evaluation of the re-epithelialization ability of two different preparations containing a recently synthetized HA cross-linked with urea: 0.02% (w/v) HA-CL (solution 1, S1), and 0.4% (w/v) HA-CL (solution 2, S2). The study was conducted on both 2D human corneal cells (HCEpiC) and 3D reconstructed tissues of human corneal epithelium (HCE). Viability by 3(4,5-dimethylthiazol-2)2,5-diphenyltetrazolium bromide (MTT) test, pro-inflammatory cytokine release (interleukin-8, IL-8) by ELISA, and morphology by hematoxylin and eosin (HE) staining were evaluated. In addition, to understand the molecular basis of the re-epithelialization properties, cyclin D1 levels were assessed by western blot. The results showed no cellular toxicity, a slight decrease in IL-8 release, and restoration of epithelium integrity when the wounded 3D model was treated with S1 and S2. In parallel, cyclin D1 levels increased in cells treated with both S1 and S2. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1
Molecules 2017, 22(12), 2105; doi:10.3390/molecules22122105
Received: 11 October 2017 / Revised: 27 November 2017 / Accepted: 28 November 2017 / Published: 4 December 2017
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Abstract
Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in
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Cervical cancer is one of the most common gynecological malignant tumors worldwide, for which chemotherapeutic strategies are limited due to their non-specific cytotoxicity and drug resistance. The natural product thymoquinone (TQ) has been reported to target a vast number of signaling pathways in carcinogenesis in different cancers, and hence is regarded as a promising anticancer molecule. Inhibition of epithelial to mesenchymal transition (EMT) regulators is an important approach in anticancer research. In this study, TQ was used to treat the cervical cancer cell lines SiHa and CaSki to investigate its effects on EMT-regulatory proteins and cancer metastasis. Our results showed that TQ has time-dependent and dose-dependent cytotoxic effects, and it also inhibits the migration and invasion processes in different cervical cancer cells. At the molecular level, TQ treatment inhibited the expression of Twist1, Zeb1 expression, and increased E-Cadherin expression. Luciferase reporter assay showed that TQ decreases the Twist1 and Zeb1 promoter activities respectively, indicating that Twist1 and Zeb1 might be the direct target of TQ. TQ also increased cellular apoptosis in some extent, but apoptotic genes/proteins we tested were not significant affected. We conclude that TQ inhibits the migration and invasion of cervical cancer cells, probably via Twist1/E-Cadherin/EMT or/and Zeb1/E-Cadherin/EMT, among other signaling pathways. Full article
(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)
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Open AccessArticle One-Step Partially Purified Lipases (ScLipA and ScLipB) from Schizophyllum commune UTARA1 Obtained via Solid State Fermentation and Their Applications
Molecules 2017, 22(12), 2106; doi:10.3390/molecules22122106
Received: 9 October 2017 / Revised: 29 November 2017 / Accepted: 29 November 2017 / Published: 8 December 2017
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Abstract
Lipases with unique characteristics are of value in industrial applications, especially those targeting cost-effectiveness and less downstream processes. The aims of this research were to: (i) optimize the fermentation parameters via solid state fermentation (SSF); and (ii) study the performance in hydrolysis and
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Lipases with unique characteristics are of value in industrial applications, especially those targeting cost-effectiveness and less downstream processes. The aims of this research were to: (i) optimize the fermentation parameters via solid state fermentation (SSF); and (ii) study the performance in hydrolysis and esterification processes of the one-step partially purified Schizophyllum commune UTARA1 lipases. Lipase was produced by cultivating S. commune UTARA1 on sugarcane bagasse (SB) with used cooking oil (UCO) via SSF and its production was optimized using Design-Expert® 7.0.0. Fractions 30% (ScLipA) and 70% (ScLipB) which contained high lipase activity were obtained by stepwise (NH4)2SO4 precipitation. Crude fish oil, coconut oil and butter were used to investigate the lipase hydrolysis capabilities by a free glycerol assay. Results showed that ScLipA has affinities for long, medium and short chain triglycerides, as all the oils investigated were degraded, whereas ScLipB has affinities for long chain triglycerides as it only degrades crude fish oil. During esterification, ScLipA was able to synthesize trilaurin and triacetin. Conversely, ScLipB was specific towards the formation of 2-mono-olein and triacetin. From the results obtained, it was determined that ScLipA and ScLipB are sn-2 regioselective lipases. Hence, the one-step partial purification strategy proved to be feasible for partial purification of S. commune UTARA1 lipases that has potential use in industrial applications. Full article
(This article belongs to the Special Issue Lipases and Lipases Modification)
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Open AccessArticle Phenylpropionamides, Piperidine, and Phenolic Derivatives from the Fruit of Ailanthus altissima
Molecules 2017, 22(12), 2107; doi:10.3390/molecules22122107
Received: 2 November 2017 / Revised: 21 November 2017 / Accepted: 29 November 2017 / Published: 4 December 2017
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Abstract
Four novel compounds—two phenylpropionamides, one piperidine, and one phenolic derivatives—were isolated and identified from the fruit of a medicinal plant, Ailanthus altissima (Mill.) Swingle (Simaroubaceae), together with one known phenylpropionamide, 13 known phenols, and 10 flavonoids. The structures of the new compounds were
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Four novel compounds—two phenylpropionamides, one piperidine, and one phenolic derivatives—were isolated and identified from the fruit of a medicinal plant, Ailanthus altissima (Mill.) Swingle (Simaroubaceae), together with one known phenylpropionamide, 13 known phenols, and 10 flavonoids. The structures of the new compounds were elucidated as 2-hydroxy-N-[(2-O-β-d-glucopyranosyl)phenyl]propionamide (1), 2-hydroxy-N-[(2-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)phenyl]propionamide (2), 2β-carboxyl-piperidine-4β-acetic acid methyl ester (4), and 4-hydroxyphenyl-1-O-[6-(hydrogen-3-hydroxy-3-methylpentanedioate)]-β-d-glucopyranoside (5) based on spectroscopic analysis. All the isolated compounds were evaluated for their inhibitory activity against Tobacco mosaic virus (TMV) using the leaf-disc method. Among the compounds isolated, arbutin (6), β-d-glucopyranosyl-(1→6)-arbutin (7), 4-methoxyphenylacetic acid (10), and corilagin (18) showed moderate inhibition against TMV with IC50 values of 0.49, 0.51, 0.27, and 0.45 mM, respectively. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Evaluation of Poly(Lactic-co-glycolic) Acid Alone or in Combination with Hydroxyapatite on Human-Periosteal Cells Bone Differentiation and in Sinus Lift Treatment
Molecules 2017, 22(12), 2109; doi:10.3390/molecules22122109
Received: 6 October 2017 / Revised: 27 November 2017 / Accepted: 27 November 2017 / Published: 2 December 2017
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Abstract
Most recent advances in tissue engineering in the fields of oral surgery and dentistry have aimed to restore hard and soft tissues. Further improvement of these therapies may involve more biological approaches and the use of dental tissue stem cells in combination with
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Most recent advances in tissue engineering in the fields of oral surgery and dentistry have aimed to restore hard and soft tissues. Further improvement of these therapies may involve more biological approaches and the use of dental tissue stem cells in combination with inorganic/organic scaffolds. In this study, we analyzed the osteoconductivity of two different inorganic scaffolds based on poly (lactic-co-glycolic) acid alone (PLGA-Fisiograft) or in combination with hydroxyapatite (PLGA/HA-Alos) in comparison with an organic material based on equine collagen (PARASORB Sombrero) both in vitro and in vivo. We developed a simple in vitro model in which periosteum-derived stem cells were grown in contact with chips of these scaffolds to mimic bone mineralization. The viability of cells and material osteoconductivity were evaluated by osteogenic gene expression and histological analyses at different time points. In addition, the capacity of scaffolds to improve bone healing in sinus lift was examined. Our results demonstrated that the osteoconductivity of PLGA/HA-Alos and the efficacy of scaffolds in promoting bone healing in the sinus lift were increased. Thus, new clinical approaches in sinus lift follow-up should be considered to elucidate the clinical potential of these two PLGA-based materials in dentistry. Full article
(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)
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Open AccessArticle Metabolomics Strategy Using High Resolution Mass Spectrometry Reveals Novel Biomarkers and Pain-Relief Effect of Traditional Chinese Medicine Prescription Wu-Zhu-Yu Decoction Acting on Headache Modelling Rats
Molecules 2017, 22(12), 2110; doi:10.3390/molecules22122110 (registering DOI)
Received: 23 October 2017 / Revised: 26 November 2017 / Accepted: 30 November 2017 / Published: 18 December 2017
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Abstract
Headache is a common episodic or chronic neurologic disorder. Treatment options and diagnosis are restricted by an incomplete understanding of disease pathology and the lack of diagnostic markers. Wu-Zhu-Yu decoction (WZYD), a traditional Chinese medicine (TCM) formula containing four TCM herbs, is commonly
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Headache is a common episodic or chronic neurologic disorder. Treatment options and diagnosis are restricted by an incomplete understanding of disease pathology and the lack of diagnostic markers. Wu-Zhu-Yu decoction (WZYD), a traditional Chinese medicine (TCM) formula containing four TCM herbs, is commonly used in the treatment of headache in China. To deeply understand more about headache and investigate the pain-relief mechanism of WZYD, a comprehensive metabolomics study combined with multivariate data processing strategy was carried out. An LC-high resolution mass spectrometry-based metabolomics approach was applied to characterize metabolic biomarker candidates. Multiple pattern recognition including principal component analysis-discriminant analysis, partial least squares-discriminant analysis and hierarchical cluster analysis were used to determine groups and confirm important variables. A total of 17 potential biomarkers were characterized and related metabolic pathways were identified. The study demonstrated that the established metabolomics strategy is a powerful approach for investigating the mechanism of headache attack and WZYD. In addition, the approach may highlight biomarkers and metabolic pathways and can capture subtle metabolite changes from headache, which may lead to an improved mechanism understanding of central nervous system diseases and TCM treatment. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Blue and Red LED Illumination Improves Growth and Bioactive Compounds Contents in Acyanic and Cyanic Ocimum basilicum L. Microgreens
Molecules 2017, 22(12), 2111; doi:10.3390/molecules22122111
Received: 30 October 2017 / Revised: 29 November 2017 / Accepted: 29 November 2017 / Published: 30 November 2017
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Abstract
Microgreens are an excellent source of health-maintaining compounds, and the accumulation of these compounds in plant tissues may be stimulated by exogenous stimuli. While light quality effects on green basil microgreens are known, the present paper aims at improving the quality of acyanic
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Microgreens are an excellent source of health-maintaining compounds, and the accumulation of these compounds in plant tissues may be stimulated by exogenous stimuli. While light quality effects on green basil microgreens are known, the present paper aims at improving the quality of acyanic (green) and cyanic (red) basil microgreens with different ratios of LED blue and red illumination. Growth, assimilatory and anthocyanin pigments, chlorophyll fluorescence, total phenolic, flavonoids, selected phenolic acid contents and antioxidant activity were assessed in microgreens grown for 17 days. Growth of microgreens was enhanced with predominantly blue illumination, larger cotyledon area and higher fresh mass. The same treatment elevated chlorophyll a and anthocyanin pigments contents. Colored light treatments decreased chlorophyll fluorescence ΦPSII values significantly in the green cultivar. Stimulation of phenolic synthesis and free radical scavenging activity were improved by predominantly red light in the green cultivar (up to 1.87 fold) and by predominantly blue light in the red cultivar (up to 1.73 fold). Rosmarinic and gallic acid synthesis was higher (up to 15- and 4-fold, respectively, compared to white treatment) in predominantly blue illumination. Red and blue LED ratios can be tailored to induce superior growth and phenolic contents in both red and green basil microgreens, as a convenient tool for producing higher quality foods. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A New Series of Pyrrole-Based Chalcones: Synthesis and Evaluation of Antimicrobial Activity, Cytotoxicity, and Genotoxicity
Molecules 2017, 22(12), 2112; doi:10.3390/molecules22122112
Received: 3 November 2017 / Revised: 27 November 2017 / Accepted: 28 November 2017 / Published: 30 November 2017
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Abstract
In an effort to develop new potent antimicrobial and anticancer agents, new pyrrole-based chalcones were designed and synthesized via the base-catalyzed Claisen-Schmidt condensation of 2-acetyl-1-methylpyrrole with 5-(aryl)furfural derivatives. The compounds were evaluated for their in vitro antimicrobial effects on pathogenic bacteria and Candida
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In an effort to develop new potent antimicrobial and anticancer agents, new pyrrole-based chalcones were designed and synthesized via the base-catalyzed Claisen-Schmidt condensation of 2-acetyl-1-methylpyrrole with 5-(aryl)furfural derivatives. The compounds were evaluated for their in vitro antimicrobial effects on pathogenic bacteria and Candida species using microdilution and ATP luminescence microbial cell viability assays. MTT assay was performed to determine the cytotoxic effects of the compounds on A549 human lung adenocarcinoma, HepG2 human hepatocellular carcinoma, C6 rat glioma, and NIH/3T3 mouse embryonic fibroblast cell lines. 1-(1-Methyl-1H-pyrrol-2-yl)-3-(5-(4-chlorophenyl)furan-2-yl)prop-2-en-1-one (7) and 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(2,5-dichlorophenyl)furan-2-yl)prop-2-en-1-one (9) were found to be the most potent antifungal agents against Candida krusei and therefore these compounds were chosen for flow cytometry analysis and Ames MPF assay. ATP bioluminescence assay indicated that the antifungal activity of compounds 7 and 9 against C. krusei was significantly higher than that of other compounds and the reference drug (ketoconazole), whereas flow cytometry analysis revealed that the percentage of dead cells treated with compound 7 was more than that treated with compound 9 and ketoconazole. According to Ames MPF assay, compounds 7 and 9 were found to be non-genotoxic against TA98 and TA100 with/without metabolic activation. MTT assay indicated that 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(2-nitrophenyl)furan-2-yl)prop-2-en-1-one (3) showed more selective anticancer activity than cisplatin against the HepG2 cell line. On the other hand, 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(4-nitrophenyl)furan-2-yl)prop-2-en-1-one (1) was found to be more effective and selective on the A549 cell line than cisplatin. Full article
(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)
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Open AccessFeature PaperArticle Controlled Synthesis of Monodisperse Hexagonal NaYF4:Yb/Er Nanocrystals with Ultrasmall Size and Enhanced Upconversion Luminescence
Molecules 2017, 22(12), 2113; doi:10.3390/molecules22122113
Received: 3 November 2017 / Revised: 24 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
The ability to synthesize upconversion nanocrystals (UCNCs) with tailored upconversion luminescence and controlled size is of great importance for biophotonic applications. However, until now, limited success has been met to prepare bright, ultrasmall, and monodispersed β-NaYF4:Yb3+/Er3+ UCNCs. In
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The ability to synthesize upconversion nanocrystals (UCNCs) with tailored upconversion luminescence and controlled size is of great importance for biophotonic applications. However, until now, limited success has been met to prepare bright, ultrasmall, and monodispersed β-NaYF4:Yb3+/Er3+ UCNCs. In this work, we report on a synthetic method to produce monodisperse hexagonal NaYF4:Yb3+/Er3+ nanocrystals of ultrasmall size (5.4 nm) through a precise control of the reaction temperature and the ratio of Na+/Ln3+/F. We determined the optimum activator concentration of Er3+ to be 6.5 mol % for these UCNCs, yielding about a 5-fold higher upconversion luminescence (UCL) intensity than the commonly used formula of NaYF4:30% Yb3+/2% Er3+. Moreover, a thin epitaxial shell (thickness, 1.9 nm) of NaLnF4 (Ln = Y, Gd, Lu) was grown onto these ultrasmall NaYF4:Yb3+/Er3+ NCs, enhancing its UCL by about 85-, 70- and 50-fold, respectively. The achieved sub-10-nm core and core–shell hexagonal NaYF4:Yb3+/Er3+ UCNCs with enhanced UCL have strong potential applications in bioapplications such as bioimaging and biosensing. Full article
(This article belongs to the Special Issue Lanthanide Luminescence: Fundamental Research and Applications)
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Open AccessArticle Multi Component Reactions under Increased Pressure: On the Mechanism of Formation of Pyridazino[5,4,3-de][1,6]naphthyridine Derivatives by the Reaction of Malononitrile, Aldehydes and 2-Oxoglyoxalarylhydrazones in Q-Tubes
Molecules 2017, 22(12), 2114; doi:10.3390/molecules22122114
Received: 16 October 2017 / Revised: 27 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
Efficient synthesis of phenanthridin-6(5H)-one derivatives 12an in a four-component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in Q-Tubes is reported. The results showed that the methodology has the advantage of being a one-pot synthesis of tricyclic systems in
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Efficient synthesis of phenanthridin-6(5H)-one derivatives 12an in a four-component reaction of aldehyde hydrazone, aromatic aldehydes and malononitrile in Q-Tubes is reported. The results showed that the methodology has the advantage of being a one-pot synthesis of tricyclic systems in good yields. Potential routes leading to formation of compounds 12 are discussed. The structures of the synthesized compounds could be unequivocally established via X-ray crystal structure determination and spectroscopic methods. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessFeature PaperArticle Melatonin Pharmacokinetics Following Oral Administration in Preterm Neonates
Molecules 2017, 22(12), 2115; doi:10.3390/molecules22122115
Received: 9 November 2017 / Revised: 29 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was
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Melatonin possesses potential efficacy in perinatal brain injuries, and has been proposed as adjunctive pharmacological therapy in combination with hypothermia in the clinical setting. However, the pharmacokinetics of melatonin in preterm and term newborns is still unknown. The aim of this study was to analyze the pharmacokinetics of melatonin after intragastric administration in preterm infants. Preterm newborns were enrolled 24–72 h after birth, and randomly assigned to three groups receiving a single bolus of 0.5 mg·kg−1 melatonin, or 3 boluses of 1 or 5 mg·kg−1 of melatonin at 24-h intervals. Blood samples were collected before and at selective times after melatonin administration. The half-life of melatonin in plasma ranged from 7.98 to 10.94 h, and the area under the curve (AUC) from 10.48 to 118.17 µg·mL−1·h−1. Our results indicate a different pharmacokinetic profile in premature newborns, compared to adults and experimental animals. The high peak plasma concentrations and the long half-life indicate that in the neonatal clinical setting, it is possible to obtain and maintain high serum concentrations using a single administration of melatonin repeated every 12/24 h. Full article
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Open AccessArticle An Interface for Biomedical Big Data Processing on the Tianhe-2 Supercomputer
Molecules 2017, 22(12), 2116; doi:10.3390/molecules22122116
Received: 25 October 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
Big data, cloud computing, and high-performance computing (HPC) are at the verge of convergence. Cloud computing is already playing an active part in big data processing with the help of big data frameworks like Hadoop and Spark. The recent upsurge of high-performance computing
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Big data, cloud computing, and high-performance computing (HPC) are at the verge of convergence. Cloud computing is already playing an active part in big data processing with the help of big data frameworks like Hadoop and Spark. The recent upsurge of high-performance computing in China provides extra possibilities and capacity to address the challenges associated with big data. In this paper, we propose Orion—a big data interface on the Tianhe-2 supercomputer—to enable big data applications to run on Tianhe-2 via a single command or a shell script. Orion supports multiple users, and each user can launch multiple tasks. It minimizes the effort needed to initiate big data applications on the Tianhe-2 supercomputer via automated configuration. Orion follows the “allocate-when-needed” paradigm, and it avoids the idle occupation of computational resources. We tested the utility and performance of Orion using a big genomic dataset and achieved a satisfactory performance on Tianhe-2 with very few modifications to existing applications that were implemented in Hadoop/Spark. In summary, Orion provides a practical and economical interface for big data processing on Tianhe-2. Full article
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Open AccessArticle γPNA FRET Pair Miniprobes for Quantitative Fluorescent In Situ Hybridization to Telomeric DNA in Cells and Tissue
Molecules 2017, 22(12), 2117; doi:10.3390/molecules22122117
Received: 27 October 2017 / Revised: 24 November 2017 / Accepted: 29 November 2017 / Published: 2 December 2017
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Abstract
Measurement of telomere length by fluorescent in situ hybridization is widely used for biomedical and epidemiological research, but there has been relatively little development of the technology in the 20 years since it was first reported. This report describes the use of dual
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Measurement of telomere length by fluorescent in situ hybridization is widely used for biomedical and epidemiological research, but there has been relatively little development of the technology in the 20 years since it was first reported. This report describes the use of dual gammaPNA (γPNA) probes that hybridize at alternating sites along a telomere and give rise to Förster resonance energy transfer (FRET) signals. Bright staining of telomeres is observed in nuclei, chromosome spreads and tissue samples. The use of FRET detection also allows for elimination of wash steps, normally required to remove unhybridized probes that would contribute to background signals. We found that these wash steps can diminish the signal intensity through the removal of bound, as well as unbound probes, so eliminating these steps not only accelerates the process but also enhances the quality of staining. Thus, γPNA FRET pairs allow for brighter and faster staining of telomeres in a wide range of research and clinical formats. Full article
(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)
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Open AccessArticle Optimization of Bioactive Polyphenols Extraction from Picea Mariana Bark
Molecules 2017, 22(12), 2118; doi:10.3390/molecules22122118
Received: 30 October 2017 / Revised: 30 November 2017 / Accepted: 30 November 2017 / Published: 1 December 2017
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Abstract
Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the hot water extract of Picea mariana bark was demonstrated to contain highly valuable bioactive polyphenols. In order to improve the recovery of these molecules, an optimization of the extraction was performed using water. Several
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Reported for its antioxidant, anti-inflammatory and non-toxicity properties, the hot water extract of Picea mariana bark was demonstrated to contain highly valuable bioactive polyphenols. In order to improve the recovery of these molecules, an optimization of the extraction was performed using water. Several extraction parameters were tested and extracts obtained analyzed both in terms of relative amounts of different phytochemical families and of individual molecules concentrations. As a result, low temperature (80 °C) and low ratio of bark/water (50 mg/mL) were determined to be the best parameters for an efficient polyphenol extraction and that especially for low molecular mass polyphenols. These were identified as stilbene monomers and derivatives, mainly stilbene glucoside isorhapontin (up to 12.0% of the dry extract), astringin (up to 4.6%), resveratrol (up to 0.3%), isorhapontigenin (up to 3.7%) and resveratrol glucoside piceid (up to 3.1%) which is here reported for the first time for Picea mariana. New stilbene derivatives, piceasides O and P were also characterized herein as new isorhapontin dimers. This study provides novel information about the optimal extraction of polyphenols from black spruce bark, especially for highly bioactive stilbenes including the trans-resveratrol. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Anti-Proliferative Activity of Triterpenoids and Sterols Isolated from Alstonia scholaris against Non-Small-Cell Lung Carcinoma Cells
Molecules 2017, 22(12), 2119; doi:10.3390/molecules22122119
Received: 31 October 2017 / Revised: 28 November 2017 / Accepted: 30 November 2017 / Published: 1 December 2017
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Abstract
(1) Background: In China and South Asia, Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in traditional ethnopharmacy to treat infectious diseases. Although various pharmacological activities have been reported, the anti-lung cancer components of A. scholaris have not
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(1) Background: In China and South Asia, Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in traditional ethnopharmacy to treat infectious diseases. Although various pharmacological activities have been reported, the anti-lung cancer components of A. scholaris have not yet been identified. The objective of this study is to evaluate the active components of the leaf extract of A. scholaris, and assess the anti-proliferation effects of isolated compounds against non-small-cell lung carcinoma cells; (2) Methods: NMR was used to identify the chemical constitutes isolated from the leaf extract of A. scholaris. The anti-proliferative activity of compounds against non-small-cell lung carcinoma cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (3) Results: Eight triterpenoids and five sterols were isolated from the hexane portion of A. scholaris, and structurally identified as: (1) ursolic acid, (2) oleanolic acid, (3) betulinic acid, (4) betulin, (5) 2β,3β,28-lup-20(29)-ene-triol, (6) lupeol, (7) β-amyrin, (8) α-amyrin, (9) poriferasterol, (10) epicampesterol, (11) β-sitosterol, (12) 6β-hydroxy-4-stigmasten-3-one, and (13) ergosta-7,22-diene-3β,5α,6β-triol. Compound 5 was isolated from a plant source for the first time. In addition, compounds 9, 10, 12, and 13 were also isolated from A. scholaris for the first time. Ursolic acid, betulinic acid, betulin, and 2β,3β,28-lup-20(29)-ene-triol showed anti-proliferative activity against NSCLC, with IC50 of 39.8, 40.1, 240.5 and 172.6 μM, respectively.; (4) Conclusion: These findings reflect that pentacyclic triterpenoids are the anti-lung cancer chemicals in A. scholaris. The ability of ursolic acid, betulinic acid, betulin, and 2β,3β,28-lup-20(29)-ene-triol to inhibit the proliferative activity of NSCLC can constitute a valuable group of therapeutic agents in the future. Full article
(This article belongs to the Special Issue Diversity of Terpenoids)
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Open AccessArticle Theoretical Study of ClOO + NO Reaction: Mechanism and Kinetics
Molecules 2017, 22(12), 2121; doi:10.3390/molecules22122121
Received: 30 October 2017 / Revised: 16 November 2017 / Accepted: 20 November 2017 / Published: 1 December 2017
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Abstract
Theoretical investigations are performed on mechanism and kinetics of the reaction of halogen peroxy radical ClOO with NO radical. The electronic structure information for both of the singlet and triplet potential energy surfaces (PESs) is obtained at the MP2/6-311 + G(2df) level of
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Theoretical investigations are performed on mechanism and kinetics of the reaction of halogen peroxy radical ClOO with NO radical. The electronic structure information for both of the singlet and triplet potential energy surfaces (PESs) is obtained at the MP2/6-311 + G(2df) level of theory, and the single-point energies are refined by the CCSD(T)/6-311 + G(2df) level. The rate constants for various product channels of the reaction in the pressure range of 1-7600 Torr are predicted. The main results are as follows: On the singlet surface, the addition-elimination mechanism is the most important. First, the N atom of the NO radical can attack the O atom of the ClOO radical to form an energy-riched intermediate IM1 ClOONOtp (21.3 kcal/mol) barrierlessly, then IM1 could isomerizes to IM2 ClOONOcp (22.1 kcal/mol) via a low energy barrier. Both IM1 and IM2 can dissociate to the primary product P1 ClNO + 1O2 and the secondary product P2 ClO + NO2. On the triplet surface, the direct Cl-abstraction reaction is the most feasible pathway. The Cl-abstraction can take place via a van der Waals complex, 3IM1 ONClOO (4.1 kcal/mol), then it fragments readily to give P1’ ClNO + 3O2 with a small barrier. The kinetic calculations show that at low temperatures, the singlet bimolecular product P1 is the primary product, while at high temperatures, the triplet product P1’ becomes the primary one; only at high pressures and low temperatures, the unimolecular products IM1 and IM2 can be found with quite small yields. At experimentally measured temperature 213 K, ClNO is the primary product in the whole pressure range, which is consistent with the previous experiment. The present study may be useful for further experimental studies for the title reaction. Full article
(This article belongs to the Special Issue Radical Chemistry)
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Open AccessArticle Comparative Evaluation of Chemical Profiles of Pyrrosiae Folium Originating from Three Pyrrosia Species by HPLC-DAD Combined with Multivariate Statistical Analysis
Molecules 2017, 22(12), 2122; doi:10.3390/molecules22122122
Received: 6 November 2017 / Revised: 29 November 2017 / Accepted: 30 November 2017 / Published: 1 December 2017
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Abstract
Pyrrosiae Folium (PF) is a commonly used Chinese herb medicine originating from three Pyrrosia species for the treatment of urinary infection and urolithiasis. According to Chinese medicine practice, different specie origins led to some variations in the therapeutic effects of PF. To ensure
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Pyrrosiae Folium (PF) is a commonly used Chinese herb medicine originating from three Pyrrosia species for the treatment of urinary infection and urolithiasis. According to Chinese medicine practice, different specie origins led to some variations in the therapeutic effects of PF. To ensure the safety and efficacy of PF in clinical practice, it is necessary to establish a reliable and integrative method to distinguish PF occurring from the three species. In the present paper, a HPLC–DAD method was developed and applied to simultaneously analyze five major compounds in PF. Afterwards, multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied for specie discrimination and integrative quality evaluation based on quantitative data. The chemical determination and pattern recognition results of 35 batches of PF samples indicated that PF samples from three species showed different chemical profiles and could be discriminated clearly. In conclusion, the present method is rapid and reliable for the quality assessment and species discrimination of PF. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle QNA-Based Prediction of Sites of Metabolism
Molecules 2017, 22(12), 2123; doi:10.3390/molecules22122123
Received: 9 November 2017 / Revised: 30 November 2017 / Accepted: 28 November 2017 / Published: 1 December 2017
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Abstract
Metabolism of xenobiotics (Greek xenos: exogenous substances) plays an essential role in the prediction of biological activity and testing for the subsequent research and development of new drug candidates. Integration of various methods and techniques using different computational and experimental approaches is
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Metabolism of xenobiotics (Greek xenos: exogenous substances) plays an essential role in the prediction of biological activity and testing for the subsequent research and development of new drug candidates. Integration of various methods and techniques using different computational and experimental approaches is one of the keys to a successful metabolism prediction. While multiple structure-based and ligand-based approaches to metabolism prediction exist, the most important problem arises at the first stage of metabolism prediction: detection of the sites of metabolism (SOMs). In this paper, we describe the application of Quantitative Neighborhoods of Atoms (QNA) descriptors for prediction of the SOMs using potential function method, as well as several different machine learning techniques: naïve Bayes, random forest classifier, multilayer perceptron with back propagation and convolutional neural networks, and deep neural networks. Full article
(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)
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Open AccessArticle Synthesis, Characterization and Antibacterial Activity of Novel 1,3-Diethyl-1,3-bis(4-nitrophenyl)urea and Its Metal(II) Complexes
Molecules 2017, 22(12), 2125; doi:10.3390/molecules22122125
Received: 28 October 2017 / Revised: 24 November 2017 / Accepted: 27 November 2017 / Published: 2 December 2017
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Abstract
A bioactive ligand and its dinuclear metal(II) complexes were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-Visible), nuclear magnetic resonance (1H-NMR), mass spectroscopy and molar conductance measurements. The ligand has been crystalized in the monoclinic system with a P21/c
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A bioactive ligand and its dinuclear metal(II) complexes were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible (UV-Visible), nuclear magnetic resonance (1H-NMR), mass spectroscopy and molar conductance measurements. The ligand has been crystalized in the monoclinic system with a P21/c space group. The biological activities of metal complexes were evaluated using disc diffusion and broth dilution methods. In vitro antibacterial activities of the ligand and their metal complexes were examined against two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Serratia marcescens) and compared to the standard drugs. It was found that metal complexes displayed much higher antibacterial activities and better inhibitory effects than that of the ligand and standard drugs. Among these complexes, the compound having Zn-metal showed greater antibacterial activity against all four tested bacteria and was more effective against Serratia marcescens with the zone inhibition diameter of 26 mm and MIC value of 31.25 µg/mL. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Biochemical, Physiological and Transcriptomic Comparison between Burley and Flue-Cured Tobacco Seedlings in Relation to Carbohydrates and Nitrate Content
Molecules 2017, 22(12), 2126; doi:10.3390/molecules22122126
Received: 7 November 2017 / Revised: 21 November 2017 / Accepted: 28 November 2017 / Published: 2 December 2017
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Abstract
Burley tobacco is a genotype of chloroplast-deficient mutant with accumulates high levels of tobacco-specific nitrosamines (TSNAs) which would induce malignant tumors in animals. Nitrate is a principle precursor of tobacco-specific nitrosamines. Nitrate content in burley tobacco was significantly higher than that in flue-cured
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Burley tobacco is a genotype of chloroplast-deficient mutant with accumulates high levels of tobacco-specific nitrosamines (TSNAs) which would induce malignant tumors in animals. Nitrate is a principle precursor of tobacco-specific nitrosamines. Nitrate content in burley tobacco was significantly higher than that in flue-cured tobacco. The present study investigated differences between the two tobacco types to explore the mechanisms of nitrate accumulation in burley tobacco. transcripts (3079) related to the nitrogen and carbon metabolism were observed. Expression of genes involved in carbon fixation, glucose and starch biosynthesis, nitrate translocation and assimilation were significantly low in burley tobacco than flue-cured tobacco. Being relative to flue-cured tobacco, burley tobacco was significantly lower at total nitrogen and carbohydrate content, nitrate reductase and glutamine synthetase activities, chlorophyll content and photosynthetic rate (Pn), but higher nitrate content. Burley tobacco required six-fold more nitrogen fertilizers than flue-cured tobacco, but both tobaccos had a similar leaf biomass. Reduced chlorophyll content and photosynthetic rate (Pn) might result in low carbohydrate formation, and low capacity of nitrogen assimilation and translocation might lead to nitrate accumulation in burley tobacco. Full article
(This article belongs to the Special Issue Design in Synthetic Biology)
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Open AccessArticle Superior Stability of Hydroxysafflor Yellow A in Xuebijing Injection and the Associated Mechanism
Molecules 2017, 22(12), 2129; doi:10.3390/molecules22122129
Received: 30 October 2017 / Revised: 26 November 2017 / Accepted: 30 November 2017 / Published: 2 December 2017
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Abstract
Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection. At first, the stability of HSYA in solution and in a Xuebijing injection was investigated, then the mechanisms of the increased stability of HSYA in the XBJ injection were investigated to
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Hydroxysafflor yellow A (HSYA) is the main bioactive ingredient of XBJ injection. At first, the stability of HSYA in solution and in a Xuebijing injection was investigated, then the mechanisms of the increased stability of HSYA in the XBJ injection were investigated to provide useful information on clinical safety. HSYA stability was investigated as a function of pH and temperature in aqueous solution and an XBJ injection, following the guidelines from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Products were identified by UPLC-MS/MS. HSYA reaction followed first-order kinetics under all conditions. The half-life of HSYA in XBJ was almost 40 times longer than in aqueous solution. The activation energies of HSYA reaction in aqueous solution and XBJ were calculated to be 78.53 and 92.90 kJ∙mol−1 by using Arrhenius equation. The results indicated that HSYA was more stable in XBJ than in aqueous solution. Two products were identified and the mechanism was intra-molecular nucleophilic substitution. The excellent stability of HSYA in XBJ injection partly due to the micelles formed in the injection. The study may provide clues for compatibility in TCM prescription and also provide useful information for further preparation technology research of HSYA and assessment of clinical safety of XBJ. Full article
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Open AccessArticle Steppogenin Isolated from Cudrania tricuspidata Shows Antineuroinflammatory Effects via NF-κB and MAPK Pathways in LPS-Stimulated BV2 and Primary Rat Microglial Cells
Molecules 2017, 22(12), 2130; doi:10.3390/molecules22122130
Received: 18 October 2017 / Revised: 21 November 2017 / Accepted: 29 November 2017 / Published: 2 December 2017
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Abstract
Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO)
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Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO) derived from inducible NO synthase (iNOS), prostaglandin E2 (PGE2) derived from cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12 (IL-12), and interleukin-6 (IL-6). These inflammatory reactions are related to the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, the modulation of NF-κB and MAPK is vital to prevent microglial activation and confer resistance against neuronal injury. In this study, steppogenin (1) isolated from Cudrania tricuspidata suppressed the neuroinflammatory responses to lipopolysaccharide (LPS). Steppogenin (1) inhibited the production of proinflammatory mediators and cytokines in LPS-challenged BV2 and rat primary microglial cells. Moreover, western blot analysis and immunofluorescence revealed that the nuclear translocation of NF-κB was inhibited in LPS-induced BV2 and rat primary microglial cells. The LPS-stimulated activation of BV2 and rat primary microglial cells was inhibited by steppogenin (1) through the suppression of c-Jun NH2-terminal kinase (JNK) and p38 MAPK signaling. These results suggested that steppogenin (1) exerted antineuroinflammatory effects against acute neuroinflammation in BV2 and rat primary microglial cells by suppressing the activation of NF-κB and MAPK signaling and the production of proinflammatory mediators and cytokines. Full article
(This article belongs to the Special Issue Plant Derived Natural Products and Age Related Diseases)
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Open AccessArticle A Robust Manifold Graph Regularized Nonnegative Matrix Factorization Algorithm for Cancer Gene Clustering
Molecules 2017, 22(12), 2131; doi:10.3390/molecules22122131
Received: 27 October 2017 / Revised: 27 November 2017 / Accepted: 29 November 2017 / Published: 2 December 2017
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Abstract
Detecting genomes with similar expression patterns using clustering techniques plays an important role in gene expression data analysis. Non-negative matrix factorization (NMF) is an effective method for clustering the analysis of gene expression data. However, the NMF-based method is performed within the Euclidean
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Detecting genomes with similar expression patterns using clustering techniques plays an important role in gene expression data analysis. Non-negative matrix factorization (NMF) is an effective method for clustering the analysis of gene expression data. However, the NMF-based method is performed within the Euclidean space, and it is usually inappropriate for revealing the intrinsic geometric structure of data space. In order to overcome this shortcoming, Cai et al. proposed a novel algorithm, called graph regularized non-negative matrices factorization (GNMF). Motivated by the topological structure of the GNMF-based method, we propose improved graph regularized non-negative matrix factorization (GNMF) to facilitate the display of geometric structure of data space. Robust manifold non-negative matrix factorization (RM-GNMF) is designed for cancer gene clustering, leading to an enhancement of the GNMF-based algorithm in terms of robustness. We combine the l 2 , 1 -norm NMF with spectral clustering to conduct the wide-ranging experiments on the three known datasets. Clustering results indicate that the proposed method outperforms the previous methods, which displays the latest application of the RM-GNMF-based method in cancer gene clustering. Full article
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Open AccessArticle Phenolic Content and Antioxidant Activity in Raw and Denatured Aqueous Extracts from Sprouts and Wheatgrass of Einkorn and Emmer Obtained under Salinity
Molecules 2017, 22(12), 2132; doi:10.3390/molecules22122132
Received: 3 November 2017 / Revised: 30 November 2017 / Accepted: 1 December 2017 / Published: 2 December 2017
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Abstract
Total phenolic content (TPC), reducing power (RP), superoxide radical scavenging (RS), and thiobarbituric acid reactive substances (TBARS) production inhibition were measured in raw and denatured aqueous extracts from sprouts and wheatgrass of einkorn and emmer obtained at increasing salinity. Grains were incubated and
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Total phenolic content (TPC), reducing power (RP), superoxide radical scavenging (RS), and thiobarbituric acid reactive substances (TBARS) production inhibition were measured in raw and denatured aqueous extracts from sprouts and wheatgrass of einkorn and emmer obtained at increasing salinity. Grains were incubated and kept at 0, 25, 50, and 100 mM NaCl until either sprout or wheatgrass stage. Additionally, a recovery treatment was included, in which sprouts obtained at 100 mM NaCl were then transferred at 0 mM NaCl until wheatgrass stage. All parameters (TPC, RP, RS, and TBARS production inhibition) increased with sprouting and were highest in wheatgrass. Salinity increased all parameters, but the effect varied with NaCl concentration, genotype, developmental stage, and plant material processing (raw or denatured). Overall, given the delay and limitation of growth at high NaCl concentration, the best compromise appears to be the application of a moderate salinity (25 to 50 mM NaCl). In denatured extracts, TPC, RP, and RS slightly decreased, and TBARS was not affected, which means that antioxidant activity was mainly related to compounds other than enzymes and peptides, and thus it can be assumed to remain after digestion. Thus, supplementing the human diet with einkorn or emmer sprouts and wheatgrass can actually benefit health. Full article
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Open AccessArticle Improving the Catalytic Property of the Glycoside Hydrolase LXYL-P1–2 by Directed Evolution
Molecules 2017, 22(12), 2133; doi:10.3390/molecules22122133
Received: 15 November 2017 / Revised: 1 December 2017 / Accepted: 2 December 2017 / Published: 4 December 2017
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Abstract
The glycoside hydrolase LXYL-P1–2 from Lentinula edodes can specifically hydrolyze 7-β-xylosyltaxanes to form 7-β-hydroxyltaxanes for the semi-synthesis of paclitaxel. In order to improve the catalytic properties of the enzyme, we performed error-prone PCR to construct the random mutant library of LXYL-P1–2 and used
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The glycoside hydrolase LXYL-P1–2 from Lentinula edodes can specifically hydrolyze 7-β-xylosyltaxanes to form 7-β-hydroxyltaxanes for the semi-synthesis of paclitaxel. In order to improve the catalytic properties of the enzyme, we performed error-prone PCR to construct the random mutant library of LXYL-P1–2 and used the methanol-induced plate method to screen the mutants with improved catalytic properties. Two variants, LXYL-P1–2-EP1 (EP1, S91D mutation) and LXYL-P1–2-EP2 (EP2, T368E mutation), were obtained from the library and exhibited 17% and 47% increases in their catalytic efficiencies on 7-β-xylosyl-10-deacetyltaxol. Meanwhile, compared with LXYL-P1–2, EP1 and EP2 showed elevated stabilities in the range of pH ≥ 6 conditions. After treatment at pH 12 for 48 h, EP1 and EP2 retained 77% and 63% activities, respectively, while the wild-type only retained 33% activity under the same condition. Molecular docking results revealed that the S91D mutation led to a shorter distance between the R-chain and the substrate, while the T368E mutation increased negative charge at the surface of the enzyme, and may introduce alterations of the loop near the active pocket, both of which may result in improved stabilities and catalytic activities of enzymes. This study provides a practical directed evolution method for exploring catalytically improved glycoside hydrolase. Full article
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Open AccessArticle A Diastereoselective Synthesis of Dispiro[oxindole-cyclohexanone]pyrrolidines by 1,3-Dipolar Cycloaddition
Molecules 2017, 22(12), 2134; doi:10.3390/molecules22122134
Received: 30 September 2017 / Revised: 29 November 2017 / Accepted: 2 December 2017 / Published: 4 December 2017
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Abstract
For the first time, arylmethylidene cyclohexanones that are non-symmetrical due to the presence of peripheral substituents were studied in 1,3-dipolar cycloaddition reactions. It is shown that the interaction with the azomethine ylide generated from sarcosine proceeds regio- and diastereoselectively, with the participation of
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For the first time, arylmethylidene cyclohexanones that are non-symmetrical due to the presence of peripheral substituents were studied in 1,3-dipolar cycloaddition reactions. It is shown that the interaction with the azomethine ylide generated from sarcosine proceeds regio- and diastereoselectively, with the participation of two non-equivalent parts of the dipolarophile. Also for the first time, β-amino ketones (Mannich bases) were used as dipolarophile equivalents of unsaturated ketones. It was found that cycloaddition occurs diastereoselectively at the generated center. Full article
(This article belongs to the Special Issue Advances in Spiro Compounds)
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Open AccessArticle Composition and Antibacterial Activity of the Essential Oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack against Pathogenic Oral Bacteria
Molecules 2017, 22(12), 2135; doi:10.3390/molecules22122135
Received: 2 November 2017 / Revised: 27 November 2017 / Accepted: 30 November 2017 / Published: 5 December 2017
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Abstract
In this study, the essential oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack were evaluated for their antibacterial activity against invasive oral pathogens, namely Enterococcus faecalis, Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and
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In this study, the essential oils of Orthosiphon stamineus Benth and Ficus deltoidea Jack were evaluated for their antibacterial activity against invasive oral pathogens, namely Enterococcus faecalis, Streptococcus mutans, Streptococcus mitis, Streptococcus salivarius, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Chemical composition of the oils was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The antibacterial activity of the oils and their major constituents were investigated using the broth microdilution method (minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC)). Susceptibility test, anti-adhesion, anti-biofilm, checkerboard and time-kill assays were also carried out. Physiological changes of the bacterial cells after exposure to the oils were observed under the field emission scanning electron microscope (FESEM). O. stamineus and F. deltoidea oils mainly consisted of sesquiterpenoids (44.6% and 60.9%, respectively), and β-caryophyllene was the most abundant compound in both oils (26.3% and 36.3%, respectively). Other compounds present in O. stamineus were α-humulene (5.1%) and eugenol (8.1%), while α-humulene (5.5%) and germacrene D (7.7%) were dominant in F. deltoidea. The oils of both plants showed moderate to strong inhibition against all tested bacteria with MIC and MBC values ranging 0.63–2.5 mg/mL. However, none showed any inhibition on monospecies biofilms. The time-kill assay showed that combination of both oils with amoxicillin at concentrations of 1× and 2× MIC values demonstrated additive antibacterial effect. The FESEM study showed that both oils produced significant alterations on the cells of Gram-negative bacteria as they became pleomorphic and lysed. In conclusion, the study indicated that the oils of O. stamineus and F. deltoidea possessed moderate to strong antibacterial properties against the seven strains pathogenic oral bacteria and may have caused disturbances of membrane structure or cell wall of the bacteria. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Monitoring the Activity of Immobilized Lipase with Quinizarin Diester Fluoro-Chromogenic Probe
Molecules 2017, 22(12), 2136; doi:10.3390/molecules22122136
Received: 1 November 2017 / Revised: 23 November 2017 / Accepted: 1 December 2017 / Published: 4 December 2017
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Abstract
Quinizarin diester is used as a fluoro-chromogenic substrate of the activity of lipase supported in poly(methylmetacrylate) beads (CALB, Novozym® 435) dispersed in organic solvents. The monoester and diester of quinizarin are both non-fluorescent species contrasting with the enzymatic product quinizarin that shows
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Quinizarin diester is used as a fluoro-chromogenic substrate of the activity of lipase supported in poly(methylmetacrylate) beads (CALB, Novozym® 435) dispersed in organic solvents. The monoester and diester of quinizarin are both non-fluorescent species contrasting with the enzymatic product quinizarin that shows optical absorption in the visible region and strong fluorescence signal. The enzymatic conversion is accomplished by spectroscopic measurements and it follows a sigmoid curve from which the mean reaction time of the enzymatic process can be determined. This parameter indicates the enzyme activity of the immobilized lipase. Its dependency with the amount of lipase allowed the determination of the ratio of the catalytic rate and the Michaelis constant (kc/Km) and the experimental value found was (1.0 ± 0.1) × 10−2 mg−1/min in the case of quinizarin diacetate. Full article
(This article belongs to the Special Issue Lipases and Lipases Modification)
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Open AccessArticle Using the SPE and Micro-HPLC-MS/MS Method for the Analysis of Betalains in Rat Plasma after Red Beet Administration
Molecules 2017, 22(12), 2137; doi:10.3390/molecules22122137
Received: 7 November 2017 / Revised: 1 December 2017 / Accepted: 2 December 2017 / Published: 4 December 2017
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Abstract
The objective of this study was to develop a simple and reproducible method for the qualitative and quantitative analysis of betalains in plasma samples, based on Solid Phase Extraction (SPE) and micro-high performance liquid chromatography coupled with mass spectrometry (micro-HPLC-MS/MS). The eight betalain
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The objective of this study was to develop a simple and reproducible method for the qualitative and quantitative analysis of betalains in plasma samples, based on Solid Phase Extraction (SPE) and micro-high performance liquid chromatography coupled with mass spectrometry (micro-HPLC-MS/MS). The eight betalain compounds detected and quantified were characterized in the fortified rat blood plasma samples. The developed method showed a good coefficient of determination (R2 = 0.999), good recovery, precision, and appropriate limits of detection (LOD) and quantification (LOQ) for these compounds. Application of this method for the treatment of rat plasma samples collected after the betalain preparation administration, for the first time, revealed the presence of native betalains and their metabolites in plasma samples. Moreover, among them, betanin (2.14 ± 0.06 µmol/L) and isobetanin (3.28 ± 0.04 µmol/L) were found at the highest concentration. The results indicated that the combination of an SPE method with a micro-HPLC-MS/MS analysis may be successfully applied for the determination of betalains in the blood plasma. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Support for Natural Small-Molecule Phenols as Anxiolytics
Molecules 2017, 22(12), 2138; doi:10.3390/molecules22122138
Received: 29 October 2017 / Revised: 30 November 2017 / Accepted: 30 November 2017 / Published: 6 December 2017
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Abstract
Natural small-molecule phenols (NSMPs) share some bioactivities. The anxiolytic activity of NSMPs is attracting attention in the scientific community. This paper provides data supporting the hypothesis that NSMPs are generally anxiolytic. The anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol, protocatechuic aldehyde,
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Natural small-molecule phenols (NSMPs) share some bioactivities. The anxiolytic activity of NSMPs is attracting attention in the scientific community. This paper provides data supporting the hypothesis that NSMPs are generally anxiolytic. The anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol, protocatechuic aldehyde, vanillin, thymol, ferulic acid, and caffeic acid, were assayed with the elevated plus maze (EPM) test in mice. The oral doses were 5, 10 and 20 mg/kg, except for phloroglucinol for which the doses were 2.5, 5 and 10 mg/kg. All tested phenols had anxiolytic activity in mice. The phenolic hydroxyl group in 4-hydroxycinnamic acid (4-OH CA) was essential for the anxiolytic activity in the EPM test in mice and rats compared to 4-chlorocinnamic acid (4-Cl CA). The in vivo spike recording of rats’ hippocampal neurons also showed significant differences between 4-OH CA and 4-Cl CA. Behavioral and neuronal spike recording results converged to indicate the hippocampal CA1 region might be a part of the anxiolytic pathways of 4-OH CA. Therefore, our study provides further experimental data supporting NSMPs sharing anxiolytic activity, which may have general implications for phytotherapy because small phenols occur extensively in herbal medicines. Full article
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Open AccessArticle (−)-Epigallocatechin-3-Gallate Inhibits the Chaperone Activity of Plasmodium falciparum Hsp70 Chaperones and Abrogates Their Association with Functional Partners
Molecules 2017, 22(12), 2139; doi:10.3390/molecules22122139
Received: 20 October 2017 / Revised: 30 November 2017 / Accepted: 1 December 2017 / Published: 5 December 2017
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Abstract
Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70 family of proteins represents one of the most important molecular chaperones in the cell. Plasmodium falciparum, the main
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Heat shock proteins (Hsps), amongst them, Hsp70 and Hsp90 families, serve mainly as facilitators of protein folding (molecular chaperones) of the cell. The Hsp70 family of proteins represents one of the most important molecular chaperones in the cell. Plasmodium falciparum, the main agent of malaria, expresses six Hsp70 isoforms. Two (PfHsp70-1 and PfHsp70-z) of these localize to the parasite cytosol. PHsp70-1 is known to occur in a functional complex with another chaperone, PfHsp90 via a co-chaperone, P. falciparum Hsp70-Hsp90 organising protein (PfHop). (−)-Epigallocatechin-3-gallate (EGCG) is a green tea constituent that is thought to possess antiplasmodial activity. However, the mechanism by which EGCG exhibits antiplasmodial activity is not fully understood. A previous study proposed that EGCG binds to the N-terminal ATPase domain of Hsp70. In the current study, we overexpressed and purified recombinant forms of two P. falciparum cytosol localized Hsp70s (PfHsp70-1 and PfHsp70-z), and PfHop, a co-chaperone of PfHsp70-1. Using the surface plasmon resonance approach, we demonstrated that EGCG directly binds to the two Hsp70s. We further observed that binding of EGCG to the two proteins resulted in secondary and tertiary conformational changes. In addition, EGCG inhibited the ATPase and chaperone function of the two proteins. Furthermore, EGCG abrogated association of the two Hsp70s with their functional partners. Using parasites cultured in vitro at the blood stages, we observed that 2.9 µM EGCG suppressed 50% P. falciparum parasite growth (IC50). Our findings demonstrate that EGCG directly binds to PfHsp70-1 and PfHsp70-z to inhibit both the ATPase and chaperone functions of the proteins. Our study constitutes the first direct evidence suggesting that the antiplasmodial activity of EGCG is at least in part accounted for by its inhibition of Hsp70 function. Full article
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