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Molecules, Volume 20, Issue 9 (September 2015), Pages 15449-17683

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Open AccessArticle Autodisplay of Human Hyaluronidase Hyal-1 on Escherichia coli and Identification of Plant-Derived Enzyme Inhibitors
Molecules 2015, 20(9), 15449-15468; doi:10.3390/molecules200915449
Received: 2 July 2015 / Revised: 17 August 2015 / Accepted: 18 August 2015 / Published: 26 August 2015
Cited by 4 | PDF Full-text (2422 KB) | HTML Full-text | XML Full-text
Abstract
Hyaluronan (HA) is the main component of the extracellular matrix (ECM). Depending on its chain size, it is generally accepted to exert diverse effects. High molecular weight HA is anti-angiogenic, immunosuppressive and anti-inflammatory, while lower fragments are angiogenic and inflammatory. Human hyaluronidase Hyal-1
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Hyaluronan (HA) is the main component of the extracellular matrix (ECM). Depending on its chain size, it is generally accepted to exert diverse effects. High molecular weight HA is anti-angiogenic, immunosuppressive and anti-inflammatory, while lower fragments are angiogenic and inflammatory. Human hyaluronidase Hyal-1 (Hyal-1) is one of the main enzymes in the metabolism of HA. This makes Hyal-1 an interesting target. Not only for functional and mechanistic studies, but also for drug development. In this work, Hyal-1 was expressed on the surface of E. coli, by applying Autodisplay, to overcome formation of inactive “inclusion bodies”. With the cells displaying Hyal-1 an activity assay was performed using “stains-all” dye. Subsequently, the inhibitory effects of four saponins and 14 plant extracts on the activity of surface displayed Hyal-1 were evaluated. The determined IC50 values were 177 µM for glycyrrhizic acid, 108 µM for gypsophila saponin 2, 371 µM for SA1657 and 296 µM for SA1641. Malvae sylvestris flos, Equiseti herba and Ononidis radix extracts showed IC50 values between 1.4 and 1.7 mg/mL. In summary, Autodisplay enabled the expression of functional human target protein Hyal-1 in E. coli and facilitated an accelerated testing of potential inhibitors. Full article
Open AccessArticle Probing Water and CO2 Interactions at the Surface of Collapsed Titania Nanotubes Using IR Spectroscopy
Molecules 2015, 20(9), 15469-15487; doi:10.3390/molecules200915469
Received: 24 April 2015 / Revised: 12 August 2015 / Accepted: 12 August 2015 / Published: 26 August 2015
Cited by 4 | PDF Full-text (2812 KB) | HTML Full-text | XML Full-text
Abstract
Collapsed titania nanotubes (cTiNT) were synthesized by the calcination of titania nanotubes (TiNT) at 650 °C, which leads to a collapse of their tubular morphology, a substantial reduction in surface area, and a partial transformation of anatase to the rutile phase. There are
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Collapsed titania nanotubes (cTiNT) were synthesized by the calcination of titania nanotubes (TiNT) at 650 °C, which leads to a collapse of their tubular morphology, a substantial reduction in surface area, and a partial transformation of anatase to the rutile phase. There are no significant changes in the position of the XPS responses for Ti and O on oxidation or reduction of the cTiNTs, but the responses are more symmetric than those observed for TiNTs, indicating fewer surface defects and no change in the oxidation state of titanium on oxidative and/or reductive pretreatment. The interaction of H2O and CO2 with the cTiNT surface was studied. The region corresponding to OH stretching absorptions extends below 3000 cm−1, and thus is broader than is typically observed for absorptions of the OH stretches of water. The exchange of protons for deuterons on exposure to D2O leads to a depletion of this extended absorption and the appearance of new absorptions, which are compatible with deuterium exchange. We discuss the source of this extended low frequency OH stretching region and conclude that it is likely due to the hydrogen-bonded OH stretches. Interaction of the reduced cTiNTs with CO2 leads to a similar but smaller set of adsorbed carbonates and bicarbonates as reported for reduced TiNTs before collapse. Implications of these observations and the presence of proton sources leading to hydrogen bonding are discussed relative to potential chemical and photochemical activity of the TiNTs. These results point to the critical influence of defect structure on CO2 photoconversion. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessArticle Synthesis, Spectral Analysis and Preliminary in Vitro Evaluation of Some Tetrapyrrolic Complexes with 3d Metal Ions
Molecules 2015, 20(9), 15488-15499; doi:10.3390/molecules200915488
Received: 20 July 2015 / Revised: 13 August 2015 / Accepted: 18 August 2015 / Published: 26 August 2015
Cited by 1 | PDF Full-text (307 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, two tetrapyrrolic complexes, Zn(II)-5-(3-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin and Cu(II)-5-(3-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin were synthesized, and characterized from a spectral and biological point of view. The study provided data concerning the behavior of identical external substituents vs. two different core insertions. Some of the properties of the
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In this paper, two tetrapyrrolic complexes, Zn(II)-5-(3-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin and Cu(II)-5-(3-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin were synthesized, and characterized from a spectral and biological point of view. The study provided data concerning the behavior of identical external substituents vs. two different core insertions. Some of the properties of the proposed tetrapyrrolic structures were highlighted, having photodynamic therapy of cancer as a targeted biomedical application. Elemental analysis, NMR, FTIR and UV-Vis data in various solvents were provided. A preliminary in vitro study on normal and cancer cultured cells was carried out for biocompatibility assessment in dark conditions. The preliminary in vitro study performed on human peripheral mononuclear cells exposed to tetrapyrrolic compounds (2 µM) showed that the proposed compounds had a convenient cytotoxic profile on human normal peripheral blood mononuclear cells under dark conditions. Meanwhile, the investigated compounds reduced the number of metabolically active breast tumor MCF-7 cells, with the exception of Zn(II) complex-containing a symmetrical ligand. Accordingly, preliminary in vitro data suggest that the proposed tetrapyrrolic compounds are good candidates for PDT, as they limit tumor expansion even under dark conditions, whilst sparing normal cells. Full article
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Open AccessArticle Identification and Antioxidant Properties of Phenolic Compounds during Production of Bread from Purple Wheat Grains
Molecules 2015, 20(9), 15525-15549; doi:10.3390/molecules200915525
Received: 3 July 2015 / Revised: 10 August 2015 / Accepted: 14 August 2015 / Published: 26 August 2015
Cited by 6 | PDF Full-text (1862 KB) | HTML Full-text | XML Full-text
Abstract
Phenolic profiles and antioxidant properties of purple wheat varieties were investigated to document the effects of bread-making. Bread crust and crumb along with samples collected after mixing, 30 min fermenting, 65 min fermenting, and baking were examined. Free phenolic content (105.4 to 113.2
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Phenolic profiles and antioxidant properties of purple wheat varieties were investigated to document the effects of bread-making. Bread crust and crumb along with samples collected after mixing, 30 min fermenting, 65 min fermenting, and baking were examined. Free phenolic content (105.4 to 113.2 mg FAE/100 g) significantly (p < 0.05) increased during mixing, fermenting, and baking (65% to 68%). Bound phenolics slightly (p > 0.05) decreased after 30 min fermentation (7% to 9%) compared to the dough after mixing, but increased significantly (p < 0.05) during 65 min fermenting and baking (16% to 27%). Their antioxidant activities followed a similar trend as observed for total phenolic content. The bread crust demonstrated increased free (103% to 109%) but decreased bound (2% to 3%) phenolic content, whereas bread crumb exhibited a reversal of these results. Total anthocyanin content (TAC) significantly (p < 0.05) decreased by 21% after mixing; however, it gradually increased to 90% of the original levels after fermenting. Baking significantly (p < 0.05) decreased TAC by 55%, resulting in the lowest value for bread crust (0.8 to 4.4 mg cyn-3-glu equiv./100 g). p-Hydroxybenzoic, vanillic, p-coumaric, and ferulic acids were detected in free-phenolic extracts, while protocatechuic, caffeic syringic, and sinapic were additional acids in bound-phenolic extracts. Cyanidin-3-glucoside was the detectable anthocyanin in purple wheat. Bread-making significantly (p < 0.05) increased the phenolic content and antioxidant activities; however, it compromised the anthocyanin content of purple wheat bread. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
Open AccessArticle Optimization of Ultrasonic-Assisted Extraction of Flavonoid Compounds and Antioxidants from Alfalfa Using Response Surface Method
Molecules 2015, 20(9), 15550-15571; doi:10.3390/molecules200915550
Received: 24 June 2015 / Revised: 7 August 2015 / Accepted: 10 August 2015 / Published: 26 August 2015
Cited by 12 | PDF Full-text (3679 KB) | HTML Full-text | XML Full-text
Abstract
Ultrasonic-assisted extraction (UAE) was used to extract flavonoid-enriched antioxidants from alfalfa aerial part. Response surface methodology (RSM), based on a four-factor, five-level central composite design (CCD), was employed to obtain the optimal extraction parameters, in which the flavonoid content was maximum and the
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Ultrasonic-assisted extraction (UAE) was used to extract flavonoid-enriched antioxidants from alfalfa aerial part. Response surface methodology (RSM), based on a four-factor, five-level central composite design (CCD), was employed to obtain the optimal extraction parameters, in which the flavonoid content was maximum and the antioxidant activity of the extracts was strongest. Radical scavenging capacity of the extracts, which represents the amounts of antioxidants in alfalfa, was determined by using 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) methods. The results showed good fit with the proposed models for the total flavonoid extraction (R2 = 0.9849), for the antioxidant extraction assayed by ABTS method (R2 = 0.9764), and by DPPH method (R2 = 0.9806). Optimized extraction conditions for total flavonoids was a ratio of liquid to solid of 57.16 mL/g, 62.33 °C, 57.08 min, and 52.14% ethanol. The optimal extraction parameters of extracts for the highest antioxidant activity by DPPH method was a ratio of liquid to solid 60.3 mL/g, 54.56 °C, 45.59 min, and 46.67% ethanol, and by ABTS assay was a ratio of liquid to solid 47.29 mL/g, 63.73 °C, 51.62 min, and 60% ethanol concentration. Our work offers optimal extraction conditions for total flavonoids and antioxidants from alfalfa. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
Open AccessArticle Studies on Cytotoxic Activity against HepG-2 Cells of Naphthoquinones from Green Walnut Husks of Juglans mandshurica Maxim
Molecules 2015, 20(9), 15572-15588; doi:10.3390/molecules200915572
Received: 20 July 2015 / Revised: 16 August 2015 / Accepted: 19 August 2015 / Published: 26 August 2015
Cited by 6 | PDF Full-text (890 KB) | HTML Full-text | XML Full-text
Abstract
Twenty-seven naphthoquinones and their derivatives, including four new naphthalenyl glucosides and twenty-three known compounds, were isolated from green walnut husks, which came from Juglans mandshurica Maxim. The structures of four new naphthalenyl glucosides were elucidated based on extensive spectroscopic analyses. All of these
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Twenty-seven naphthoquinones and their derivatives, including four new naphthalenyl glucosides and twenty-three known compounds, were isolated from green walnut husks, which came from Juglans mandshurica Maxim. The structures of four new naphthalenyl glucosides were elucidated based on extensive spectroscopic analyses. All of these compounds were evaluated for their cytotoxic activities against the growth of human cancer cells lines HepG-2 by MTT [3-(4,5-dimethylthiazo l-2-yl)-2,5 diphenyl tetrazolium bromide] assay. The results were shown that most naphthoquinones in an aglycone form exhibited better cytotoxicity in vitro than naphthalenyl glucosides with IC50 values in the range of 7.33–88.23 μM. Meanwhile, preliminary structure-activity relationships for these compounds were discussed. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Identification of N-Acetyldopamine Dimers from the Dung Beetle Catharsius molossus and Their COX-1 and COX-2 Inhibitory Activities
Molecules 2015, 20(9), 15589-15596; doi:10.3390/molecules200915589
Received: 7 July 2015 / Revised: 10 August 2015 / Accepted: 17 August 2015 / Published: 27 August 2015
Cited by 4 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recent studies focusing on identifying the biological agents of Catharsius molossus have led to the identification of three new N-acetyldopamine dimers molossusamide A–C (1-3) and two known compounds 4 and 5. The structures of the new compounds were
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Recent studies focusing on identifying the biological agents of Catharsius molossus have led to the identification of three new N-acetyldopamine dimers molossusamide A–C (1-3) and two known compounds 4 and 5. The structures of the new compounds were identified by comprehensive spectroscopic evidences. Compound 4 was found to have inhibitory effects towards COX-1 and COX-2. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Statistical Ring Opening Metathesis Copolymerization of Norbornene and Cyclopentene by Grubbs’ 1st-Generation Catalyst
Molecules 2015, 20(9), 15597-15615; doi:10.3390/molecules200915597
Received: 26 June 2015 / Revised: 18 August 2015 / Accepted: 19 August 2015 / Published: 27 August 2015
Cited by 3 | PDF Full-text (841 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Statistical copolymers of norbornene (NBE) with cyclopentene (CP) were prepared by ring-opening metathesis polymerization, employing the 1st-generation Grubbs’ catalyst, in the presence or absence of triphenylphosphine, PPh3. The reactivity ratios were estimated using the Finemann-Ross, inverted Finemann-Ross, and Kelen-Tüdos graphical methods,
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Statistical copolymers of norbornene (NBE) with cyclopentene (CP) were prepared by ring-opening metathesis polymerization, employing the 1st-generation Grubbs’ catalyst, in the presence or absence of triphenylphosphine, PPh3. The reactivity ratios were estimated using the Finemann-Ross, inverted Finemann-Ross, and Kelen-Tüdos graphical methods, along with the computer program COPOINT, which evaluates the parameters of binary copolymerizations from comonomer/copolymer composition data by integrating a given copolymerization equation in its differential form. Structural parameters of the copolymers were obtained by calculating the dyad sequence fractions and the mean sequence length, which were derived using the monomer reactivity ratios. The kinetics of thermal decomposition of the copolymers along with the respective homopolymers was studied by thermogravimetric analysis within the framework of the Ozawa-Flynn-Wall and Kissinger methodologies. Finally, the effect of triphenylphosphine on the kinetics of copolymerization, the reactivity ratios, and the kinetics of thermal decomposition were examined. Full article
(This article belongs to the Special Issue Olefin Metathesis)
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Open AccessArticle Molecular Cloning and Characterization of a Xanthone Prenyltransferase from Hypericum calycinum Cell Cultures
Molecules 2015, 20(9), 15616-15630; doi:10.3390/molecules200915616
Received: 30 June 2015 / Revised: 17 August 2015 / Accepted: 20 August 2015 / Published: 27 August 2015
Cited by 6 | PDF Full-text (1805 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In plants, prenylation of metabolites is widely distributed to generate compounds with efficient defense potential and distinct pharmacological activities profitable to human health. Prenylated compounds are formed by members of the prenyltransferase (PT) superfamily, which catalyze the addition of prenyl moieties to a
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In plants, prenylation of metabolites is widely distributed to generate compounds with efficient defense potential and distinct pharmacological activities profitable to human health. Prenylated compounds are formed by members of the prenyltransferase (PT) superfamily, which catalyze the addition of prenyl moieties to a variety of acceptor molecules. Cell cultures of Hypericum calycinum respond to elicitor treatment with the accumulation of the prenylated xanthone hyperxanthone E. A cDNA encoding a membrane-bound PT (HcPT) was isolated from a subtracted cDNA library and transcript preparations of H. calycinum. An increase in the HcPT transcript level preceded hyperxanthone E accumulation in cell cultures of H. calycinum treated with elicitor. The HcPT cDNA was functionally characterized by expression in baculovirus-infected insect cells. The recombinant enzyme catalyzed biosynthesis of 1,3,6,7-tetrahydroxy-8-prenylxanthone through regiospecific C–8 prenylation of 1,3,6,7-tetrahydroxyxanthone, indicating its involvement in hyperxanthone E formation. The enzymatic product shared significant structural features with the previously reported cholinesterase inhibitor γ-mangostin. Thus, our findings may offer a chance for semisynthesis of new active agents to be involved in the treatment of Alzheimer’s disease. Full article
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Open AccessArticle Ascorbic Acid-Initiated Tandem Radical Cyclization of N-Arylacrylamides to Give 3,3-Disubstituted Oxindoles
Molecules 2015, 20(9), 15631-15642; doi:10.3390/molecules200915631
Received: 20 July 2015 / Revised: 18 August 2015 / Accepted: 21 August 2015 / Published: 27 August 2015
PDF Full-text (858 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An ascorbic acid-promoted and metal-free tandem room temperature cyclization of N-arylacrylamides with 4-nitrobenzenediazonium generated in situ was developed. This reaction proceeds smoothly through a radical mechanism and provides an environmentally friendly alternative approach to biologically active 3-alkyl-3-benzyloxindoles, avoiding the use of excess
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An ascorbic acid-promoted and metal-free tandem room temperature cyclization of N-arylacrylamides with 4-nitrobenzenediazonium generated in situ was developed. This reaction proceeds smoothly through a radical mechanism and provides an environmentally friendly alternative approach to biologically active 3-alkyl-3-benzyloxindoles, avoiding the use of excess oxidants and light irradiation. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin
Molecules 2015, 20(9), 15643-15665; doi:10.3390/molecules200915643
Received: 6 July 2015 / Revised: 15 August 2015 / Accepted: 17 August 2015 / Published: 28 August 2015
Cited by 6 | PDF Full-text (1357 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H,
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A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (1H, 13C, 19F and 15N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure–activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Chemical Constituents and Antibacterial Properties of Indocalamus latifolius McClure Leaves, the Packaging Material for “Zongzi”
Molecules 2015, 20(9), 15686-15700; doi:10.3390/molecules200915686
Received: 27 July 2015 / Revised: 20 August 2015 / Accepted: 24 August 2015 / Published: 28 August 2015
Cited by 1 | PDF Full-text (927 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The glutinous rice dumpling named “Zongzi” in Chinese is a type of traditional food that is popular in East Asian countries. “Zongzi” is made of glutinous rice and wrapped in the leaves of Indocalamus latifolius McClure as the packaging material. Four new compounds,
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The glutinous rice dumpling named “Zongzi” in Chinese is a type of traditional food that is popular in East Asian countries. “Zongzi” is made of glutinous rice and wrapped in the leaves of Indocalamus latifolius McClure as the packaging material. Four new compounds, latifoliusine A (2), (7S,8R) syringylglycerol-8-O-4′-sinapyl ether 4-O-β-d-glucopyranoside (7), (7S,8S) syringylglycerol-8-O-4′-sinapyl ether 7-O-β-d-glucopyranoside (8), and (7R,8S) syringylglycerol-8-O-4′-sinapyl ether 7-O-β-d-glucopyranoside (10), along with six known compounds (1, 36 and 9) were isolated from I. latifolius McClure leaves. The structures and relative configurations of the compounds were determined by detailed spectroscopic analysis, high-resolution electrospray ionization mass spectroscopy (HRESIMS), heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), nuclear overhauser enhancement (NOE) and circular dichroism (CD). All of the isolated compounds were screened for their antibacterial activities in vitro. The results indicated that apigenin 6-C-α-l-arabinopyranosyl-8-C-β-d-glucopyranoside (5) and apigenin 7-O,8-C-di-glucopyranoside (6) have antibacterial activities against four bacterial strains (Staphylococcus aureus, Bacillus thuringiensis, Escherichia coli and Pseudomonas solanacearum). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Some Phthalocyanine and Naphthalocyanine Derivatives as Corrosion Inhibitors for Aluminium in Acidic Medium: Experimental, Quantum Chemical Calculations, QSAR Studies and Synergistic Effect of Iodide Ions
Molecules 2015, 20(9), 15701-15734; doi:10.3390/molecules200915701
Received: 10 July 2015 / Revised: 12 August 2015 / Accepted: 14 August 2015 / Published: 28 August 2015
Cited by 10 | PDF Full-text (3689 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The effects of seven macrocyclic compounds comprising four phthalocyanines (Pcs) namely 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine (Pc1), 2,3,9,10,16,17,23,24-octakis(octyloxy)-29H,31H-phthalocyanine (Pc2), 2,9,16,23-tetra-tert-butyl-29H,31H-phthalocyanine (Pc3) and 29H,31H-phthalocyanine (Pc4), and three naphthalocyanines namely 5,9,14,18,23,27,32,36-octabutoxy-2,3-naphthalocyanine
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The effects of seven macrocyclic compounds comprising four phthalocyanines (Pcs) namely 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine (Pc1), 2,3,9,10,16,17,23,24-octakis(octyloxy)-29H,31H-phthalocyanine (Pc2), 2,9,16,23-tetra-tert-butyl-29H,31H-phthalocyanine (Pc3) and 29H,31H-phthalocyanine (Pc4), and three naphthalocyanines namely 5,9,14,18,23,27,32,36-octabutoxy-2,3-naphthalocyanine (nPc1), 2,11,20,29-tetra-tert-butyl-2,3-naphthalocyanine (nPc2) and 2,3-naphthalocyanine (nP3) were investigated on the corrosion of aluminium (Al) in 1 M HCl using a gravimetric method, potentiodynamic polarization technique, quantum chemical calculations and quantitative structure activity relationship (QSAR). Synergistic effects of KI on the corrosion inhibition properties of the compounds were also investigated. All the studied compounds showed appreciable inhibition efficiencies, which decrease with increasing temperature from 30 °C to 70 °C. At each concentration of the inhibitor, addition of 0.1% KI increased the inhibition efficiency compared to the absence of KI indicating the occurrence of synergistic interactions between the studied molecules and I ions. From the potentiodynamic polarization studies, the studied Pcs and nPcs are mixed type corrosion inhibitors both without and with addition of KI. The adsorption of the studied molecules on Al surface obeys the Langmuir adsorption isotherm, while the thermodynamic and kinetic parameters revealed that the adsorption of the studied compounds on Al surface is spontaneous and involves competitive physisorption and chemisorption mechanisms. The experimental results revealed the aggregated interactions between the inhibitor molecules and the results further indicated that the peripheral groups on the compounds affect these interactions. The calculated quantum chemical parameters and the QSAR results revealed the possibility of strong interactions between the studied inhibitors and metal surface. QSAR analysis on the quantum chemical parameters obtained with B3LYP/6-31G (d,p) method show that a combination of two quantum chemical parameters to form a composite index provides the best correlation with the experimental data. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
Open AccessArticle Chemical Composition and Bioactivities of the Essential Oil from Etlingera yunnanensis against Two Stored Product Insects
Molecules 2015, 20(9), 15735-15747; doi:10.3390/molecules200915735
Received: 14 July 2015 / Revised: 8 August 2015 / Accepted: 21 August 2015 / Published: 28 August 2015
Cited by 7 | PDF Full-text (836 KB) | HTML Full-text | XML Full-text
Abstract
The chemical composition of the essential oil of Etlingera yunnanensis rhizomes and its contact and repellent activities against Tribolium castaneum (Herbst) and Liposcelis bostrychophila (Badonnel) were investigated. The essential oil obtained from E. yunnanensis rhizomes with hydrodistillation was performed by gas chromatography-flame
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The chemical composition of the essential oil of Etlingera yunnanensis rhizomes and its contact and repellent activities against Tribolium castaneum (Herbst) and Liposcelis bostrychophila (Badonnel) were investigated. The essential oil obtained from E. yunnanensis rhizomes with hydrodistillation was performed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. The main components of the essential oil were identified to be estragole (65.2%), β-caryophyllene (6.4%), 1,8-cineole (6.4%), limonene (5.2%), and α-pinene (2.4%). It was found that the essential oil of E. yunnanensis rhizomes possessed contact toxicity against T. castaneum and L. bostrychophila (LD50 = 23.33 μg/adult and LD50 = 47.38 μg/cm2, respectively). Estragole, 1,8-cineole, and limonene exhibited stronger contact toxicity (LD50 values of 20.41, 18.86, and 13.40 μg/adult, respectively) than β-caryophyllene (LD50 = 41.72 μg/adult) against T. castaneum adults. Estragole possessed stronger contact toxicity (LD50 = 30.22 µg/cm2) than β-caryophyllene, 1,8-cineole, and limonene (LD50 values of 74.11, 321.20, and 239.62 μg/adult, respectively) against L. bostrychophila adults. Repellency of the crude oil was also evaluated. The essential oil and constituents possessed strong repellent activity against T. castaneum adults. The four individual constituents showed weaker repellent activity than the essential oil against L. bostrychophila adults. The results indicated that the essential oil of E. yunnanensis rhizomes and the individual constituents had the potential to be developed as a natural insecticide and repellent for the control of T. castaneum and L. bostrychophila. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Antigenotoxicity and Tumor Growing Inhibition by Leafy Brassica carinata and Sinigrin
Molecules 2015, 20(9), 15748-15765; doi:10.3390/molecules200915748
Received: 26 June 2015 / Revised: 12 August 2015 / Accepted: 25 August 2015 / Published: 28 August 2015
Cited by 6 | PDF Full-text (947 KB) | HTML Full-text | XML Full-text
Abstract
Cruciferous vegetables are well known and worldwide consumed due to their health benefits and cancer prevention properties. As a desirable cruciferous plant, Ethiopian mustard (Brassica carinata A. Braun) and its glucosinolate sinigrin were tested in the in vivo Drosophila melanogaster (SMART) and
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Cruciferous vegetables are well known and worldwide consumed due to their health benefits and cancer prevention properties. As a desirable cruciferous plant, Ethiopian mustard (Brassica carinata A. Braun) and its glucosinolate sinigrin were tested in the in vivo Drosophila melanogaster (SMART) and the in vitro HL60 (human promyelocytic leukaemia cell line) systems. High performance liquid chromatography (HPLC) analysis of plant samples confirmed the presence of sinigrin as principal B. carinata glucosinolate. SMART was performed by feeding D. melanogaster larvae either with different concentrations of plant/compound samples or combining them with hydrogen peroxide (a potent oxidative mutagen) being both antimutagenics. HL60 assays showed the tumoricidal activity of plant samples (IC50 = 0.28 mg·mL−1) and the breakdown products of sinigrin hydrolysis (IC50 = 2.71 µM). Our results enhance the potential of B. carinata as health promoter and chemopreventive in both systems and the leading role of sinigrin in these effects. Full article
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Open AccessArticle Digestive Gland from Aplysia depilans Gmelin: Leads for Inflammation Treatment
Molecules 2015, 20(9), 15766-15780; doi:10.3390/molecules200915766
Received: 21 July 2015 / Revised: 15 August 2015 / Accepted: 26 August 2015 / Published: 28 August 2015
Cited by 5 | PDF Full-text (2118 KB) | HTML Full-text | XML Full-text
Abstract
The exploitation of marine organisms for human nutritional and pharmaceutical purposes has revealed important chemical prototypes for the discovery of new drugs, stimulating compounds isolation and syntheses of new related compounds with biomedical application. Nowadays, it is well known that inflammatory processes are
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The exploitation of marine organisms for human nutritional and pharmaceutical purposes has revealed important chemical prototypes for the discovery of new drugs, stimulating compounds isolation and syntheses of new related compounds with biomedical application. Nowadays, it is well known that inflammatory processes are involved in many diseases and the interest in the search for marine natural products with anti-inflammatory potential has been increasing. The genus Aplysia belongs to the class Gastropoda, having a wide geographical distribution and including several species, commonly known as sea hares. Aplysia depilans Gmelin is usually found in the Mediterranean Sea and in the Atlantic Ocean, from West Africa to the French coast. In these marine organisms, most of the digestion and nutrient absorption occurs in the digestive gland. This work aimed to explore the chemical composition and bioactivity of the methanol extract from A. depilans digestive gland. Therefore, fatty acids and carotenoids were determined by GC-MS and HPLC-DAD, respectively. Twenty-two fatty acids and eight carotenoids were identified for the first time in this species. The A. depilans digestive gland revealed to be essentially composed by polyunsaturated fatty acids (PUFA) and xanthophylls. Regarding the anti-inflammatory potential in RAW 264.7 cells stimulated with lipopolysaccharide, it was observed that this matrix has capacity to reduce nitric oxide (NO) and L-citrulline levels, which suggests that its compounds may act by interference with inducible nitric oxide synthase. Taking into account the results obtained, A. depilans digestive gland may be a good source of nutraceuticals, due to their richness in health beneficial nutrients, such as carotenoids and long-chain PUFA. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Composition, Antioxidative and Anticancer Activities of the Essential Oil: Curcumae RhizomaSparganii Rhizoma, a Traditional Herb Pair
Molecules 2015, 20(9), 15781-15796; doi:10.3390/molecules200915781
Received: 3 August 2015 / Revised: 20 August 2015 / Accepted: 25 August 2015 / Published: 28 August 2015
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Abstract
As a classical herb pair in clinics of traditional Chinese medicine, Curcumae RhizomaSparganii Rhizoma (HP CR–SR) is used for activating blood circulation to remove blood stasis. The essential components in HP CR–SR and its single herbs were comparatively analyzed using gas
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As a classical herb pair in clinics of traditional Chinese medicine, Curcumae RhizomaSparganii Rhizoma (HP CR–SR) is used for activating blood circulation to remove blood stasis. The essential components in HP CR–SR and its single herbs were comparatively analyzed using gas chromatography-mass spectrometry data. 66, 22, and 54 components in volatile oils of Curcumae Rhizoma, Sparganii Rhizoma, and HP CR–SR were identified, and total contents accounted for 75.416%, 91.857%, and 79.553% respectively. The thirty-eight components were found in HP CR–SR, and not detected in single herbs Curcumae Rhizoma and Sparganii Rhizoma. The highest radical trapping action was seen by an essential oil of HP CR–SR (IC50 = 0.59 ± 0.04 mg/mL). Furthermore, the HP CR–SR essential oil showed more remarkable cytotoxicity on tumor cell lines than that of the single herbs Curcumae Rhizoma and Sparganii Rhizoma in a dose-dependent manner: IC50 values showing 32.32 ± 5.31 μg/mL (HeLa), 34.76 ± 1.82 μg/mL (BGC823), 74.84 ± 1.66 μg/mL (MCF-7), 66.12 ± 11.23 μg/mL (SKOV3), and 708.24 ± 943.91 μg/mL (A549), respectively. In summary, the essential oil of HP CR–SR is different from any one of Curcumae Rhizoma and Sparganii Rhizoma, nor simply their superposition, and HP CR–SR oil presented more remarkable anticancer and antioxidant activities compared with Curcumae Rhizoma and Sparganii Rhizoma oils. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessCommunication Flow Synthesis of 2-Methylpyridines via α-Methylation
Molecules 2015, 20(9), 15797-15806; doi:10.3390/molecules200915797
Received: 12 August 2015 / Revised: 20 August 2015 / Accepted: 21 August 2015 / Published: 31 August 2015
Cited by 2 | PDF Full-text (765 KB) | HTML Full-text | XML Full-text
Abstract
A series of simple 2-methylpyridines were synthesized in an expedited and convenient manner using a simplified bench-top continuous flow setup. The reactions proceeded with a high degree of selectivity, producing α-methylated pyridines in a much greener fashion than is possible using conventional batch
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A series of simple 2-methylpyridines were synthesized in an expedited and convenient manner using a simplified bench-top continuous flow setup. The reactions proceeded with a high degree of selectivity, producing α-methylated pyridines in a much greener fashion than is possible using conventional batch reaction protocols. Eight 2-methylated pyridines were produced by progressing starting material through a column packed with Raney® nickel using a low boiling point alcohol (1-propanol) at high temperature. Simple collection and removal of the solvent gave products in very good yields that were suitable for further use without additional work-up or purification. Overall, this continuous flow method represents a synthetically useful protocol that is superior to batch processes in terms of shorter reaction times, increased safety, avoidance of work-up procedures, and reduced waste. A brief discussion of the possible mechanism(s) of the reaction is also presented which involves heterogeneous catalysis and/or a Ladenberg rearrangement, with the proposed methyl source as C1 of the primary alcohol. Full article
(This article belongs to the Special Issue Recent Advances in Flow Chemistry)
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Open AccessCommunication New Organocatalytic Asymmetric Synthesis of Highly Substituted Chiral 2-Oxospiro-[indole-3,4′- (1′,4′-dihydropyridine)] Derivatives
Molecules 2015, 20(9), 15807-15826; doi:10.3390/molecules200915807
Received: 17 July 2015 / Revised: 13 August 2015 / Accepted: 21 August 2015 / Published: 31 August 2015
Cited by 7 | PDF Full-text (1261 KB) | HTML Full-text | XML Full-text
Abstract
Herein, we report our preliminary results concerning the first promising asymmetric synthesis of highly functionalized 2-oxospiro-[indole-3,4′-(1′,4′-dihydropyridine)] via the reaction of an enamine with isatylidene malononitrile derivatives in the presence of a chiral base organocatalyst. The moderate, but promising, enantioselectivity observed (30%–58% ee (enantiomeric
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Herein, we report our preliminary results concerning the first promising asymmetric synthesis of highly functionalized 2-oxospiro-[indole-3,4′-(1′,4′-dihydropyridine)] via the reaction of an enamine with isatylidene malononitrile derivatives in the presence of a chiral base organocatalyst. The moderate, but promising, enantioselectivity observed (30%–58% ee (enantiomeric excess)) opens the door to a new area of research for the asymmetric construction of these appealing spirooxindole skeletons, whose enantioselective syntheses are still very limited. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle Comparison of Glucosinolate Profiles in Different Tissues of Nine Brassica Crops
Molecules 2015, 20(9), 15827-15841; doi:10.3390/molecules200915827
Received: 27 July 2015 / Revised: 14 August 2015 / Accepted: 25 August 2015 / Published: 31 August 2015
Cited by 16 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Glucosinolate (GSL) profiles and concentrations in various tissues (seeds, sprouts, mature root, and shoot) were determined and compared across nine Brassica species, including cauliflower, cabbage, broccoli, radish, baemuchae, pakchoi, Chinese cabbage, leaf mustard, and kale. The compositions and concentrations of individual GSLs varied
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Glucosinolate (GSL) profiles and concentrations in various tissues (seeds, sprouts, mature root, and shoot) were determined and compared across nine Brassica species, including cauliflower, cabbage, broccoli, radish, baemuchae, pakchoi, Chinese cabbage, leaf mustard, and kale. The compositions and concentrations of individual GSLs varied among crops, tissues, and growth stages. Seeds had highest total GSL concentrations in most of crops, whereas shoots had the lowest GSL concentrations. Aliphatic GSL concentrations were the highest in seeds, followed by that in sprouts, shoots, and roots. Indole GSL concentration was the highest in the root or shoot tissues in most of the crops. In contrast, aromatic GSL concentrations were highest in roots. Of the nine crops examined, broccoli exhibited the highest total GSL concentration in seeds (110.76 µmol·g−1) and sprouts (162.19 µmol·g−1), whereas leaf mustard exhibited the highest total GSL concentration in shoots (61.76 µmol·g−1) and roots (73.61 µmol·g−1). The lowest GSL concentrations were observed in radish across all tissues examined. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle p38α MAPK and Type I Inhibitors: Binding Site Analysis and Use of Target Ensembles in Virtual Screening
Molecules 2015, 20(9), 15842-15861; doi:10.3390/molecules200915842
Received: 26 March 2015 / Revised: 19 August 2015 / Accepted: 26 August 2015 / Published: 31 August 2015
Cited by 3 | PDF Full-text (2597 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mitogen-activated protein kinase p38α plays an essential role in the regulation of pro-inflammatory signaling, and selective blockade of this kinase could be efficacious in many pathological processes. Despite considerable research efforts focused on the discovery and development of p38α MAPK inhibitors, no drug
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Mitogen-activated protein kinase p38α plays an essential role in the regulation of pro-inflammatory signaling, and selective blockade of this kinase could be efficacious in many pathological processes. Despite considerable research efforts focused on the discovery and development of p38α MAPK inhibitors, no drug targeting this protein has been approved for clinical use so far. We herein analyze the available crystal structures of p38α MAPK in complex with ATP competitive type I inhibitors, getting insights into ATP binding site conformation and its influence on automated molecular docking results. The use of target ensembles, rather than single conformations, resulted in a performance improvement in both the ability to reproduce experimental bound conformations and the capability of mining active molecules from compound libraries. The information gathered from this study can be exploited in structure-based drug discovery programs having as the ultimate aim the identification of novel p38α MAPK type I inhibitors. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Synthesis of Phenolic Compounds by Trapping Arynes with a Hydroxy Surrogate
Molecules 2015, 20(9), 15862-15880; doi:10.3390/molecules200915862
Received: 6 August 2015 / Revised: 23 August 2015 / Accepted: 24 August 2015 / Published: 31 August 2015
Cited by 11 | PDF Full-text (889 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Trapping of arynes with various nucleophiles provides a range of heteroatom-functionalized arene derivatives, but the corresponding reaction with water does not provide phenol derivatives. Silver trifluroacetate (AgO2CCF3) can nicely solve this problem. It was found that in typical organic
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Trapping of arynes with various nucleophiles provides a range of heteroatom-functionalized arene derivatives, but the corresponding reaction with water does not provide phenol derivatives. Silver trifluroacetate (AgO2CCF3) can nicely solve this problem. It was found that in typical organic solvent, AgO2CCF3 readily reacts with arynes to generate trifluoroacetoxy organosilver arene intermediate, which, upon treating with silica gel, provides phenolic products. This protocol can be extended to the synthesis of α-halofunctionalized phenol derivatives by simply adding NBS (N-bromosuccinimides) or NIS (N-iodosuccinimides) to the reaction along with silver trifluroacetate, which provided α-bromo or α-iodophenol derivatives in good yield. However, the similar reactions with NCS (N-chlorosuccinimides) afforded only the protonated product instead of the expected α-chlorophenols derivatives. Interestingly, substrates containing silyl substituents on 1,3-diynes resulted in α-halotrifluoroacetates rather than their hydrolyzed product. Additionally, trapping the same arynes with other oxygen-based nucleophiles containing silver counter cation, along with NXS (N-halosuccinimides), generated α-halooxyfunctionalized products. Full article
(This article belongs to the Special Issue Development and Application of Aryne Chemistry in Organic Synthesis)
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Open AccessArticle Functionalization of Cyclodextrins with N-Hydroxyphthalimide Moiety: A New Class of Supramolecular Pro-Oxidant Organocatalysts
Molecules 2015, 20(9), 15881-15892; doi:10.3390/molecules200915881
Received: 28 July 2015 / Revised: 22 August 2015 / Accepted: 27 August 2015 / Published: 31 August 2015
Cited by 4 | PDF Full-text (899 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
N-hydroxyphthalimide (NHPI) is an organocatalyst for free-radical processes able to promote the aerobic oxidation of a wide range of organic substrates. In particular, NHPI can catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This property could be of interest for biological applications.
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N-hydroxyphthalimide (NHPI) is an organocatalyst for free-radical processes able to promote the aerobic oxidation of a wide range of organic substrates. In particular, NHPI can catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This property could be of interest for biological applications. This work reports the synthesis of two β-cyclodextrin derivatives (CD5 and CD6) having a different degree of methylation and bearing a NHPI moiety. These compounds, having different solubility in water, have been successfully tested for the hydroperoxidation of methyl linoleate, chosen as the PUFA model molecule. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
Molecules 2015, 20(9), 15893-15909; doi:10.3390/molecules200915893
Received: 20 July 2015 / Revised: 21 August 2015 / Accepted: 27 August 2015 / Published: 1 September 2015
Cited by 2 | PDF Full-text (1537 KB) | HTML Full-text | XML Full-text
Abstract
Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may represent a powerful
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Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may represent a powerful therapeutic tool to treat multidrug resistant GBM. We have reported that human Bak protein integrated in Liposomes (LB) was able, in vitro, to activate the mitochondrial apoptotic pathway in colon cancer cells. To evaluate the anti-tumor effects of LB on GBM, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and Western blot analysis were performed on GL26 murine cell line. LB treatment shows a dose-dependent inhibition of cell viability, followed by an up-regulation of Bax and a down-modulation of JNK1 proteins. In GL26-bearing mice, two different routes of administration were tested: intra-tumor and intravenous. Biodistribution, tumor growth and animal survival rates were followed. LB show long-lasting tumor accumulation. Moreover, the intra-tumor administration of LB induces tumor growth delay and total tumor regression in about 40% of treated mice, while the intravenous injection leads to a significant increased life span of mice paralleled by an increased tumor cells apoptosis. Our findings are functional to the design of LB with potentiated therapeutic efficacy for GBM. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Inorganic Phosphate Prevents Erk1/2 and Stat3 Activation and Improves Sensitivity to Doxorubicin of MDA-MB-231 Breast Cancer Cells
Molecules 2015, 20(9), 15910-15928; doi:10.3390/molecules200915910
Received: 7 July 2015 / Revised: 19 August 2015 / Accepted: 26 August 2015 / Published: 1 September 2015
Cited by 8 | PDF Full-text (1334 KB) | HTML Full-text | XML Full-text
Abstract
Due to its expression profile, triple-negative breast cancer (TNBC) is refractory to the most effective targeted therapies available for breast cancer treatment. Thus, cytotoxic chemotherapy represents the mainstay of treatment for early and metastatic TNBC. Therefore, it would be greatly beneficial to develop
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Due to its expression profile, triple-negative breast cancer (TNBC) is refractory to the most effective targeted therapies available for breast cancer treatment. Thus, cytotoxic chemotherapy represents the mainstay of treatment for early and metastatic TNBC. Therefore, it would be greatly beneficial to develop therapeutic approaches that cause TNBC cells to increase their sensitivity to cytotoxic drugs. Inorganic phosphate (Pi) is emerging as an important signaling molecule in many cell types. Interestingly, it has been shown that Pi greatly enhances the sensitivity of human osteosarcoma cell line (U2OS) to doxorubicin. We investigated the effects of Pi on the sensitivity of TNBC cells to doxorubicin and the underlying molecular mechanisms, carrying out flow cytometry-based assays of cell-cycle progression and cell death, MTT assays, direct cell number counting and immunoblotting experiments. We report that Pi inhibits the proliferation of triple-negative MDA-MB-231 breast cancer cells mainly by slowing down cell cycle progression. Interestingly, we found that Pi strongly increases doxorubicin-induced cytotoxicity in MDA-MB-231 cells by apoptosis induction, as revealed by a marked increase of sub-G1 population, Bcl-2 downregulation, caspase-3 activation and PARP cleavage. Remarkably, Pi/doxorubicin combination-induced cytotoxicity was dynamically accompanied by profound changes in Erk1/2 and Stat3 protein and phosphorylation levels. Altogether, our data enforce the evidence of Pi acting as a signaling molecule in MDA-MB-231 cells, capable of inhibiting Erk and Stat3 pathways and inducing sensitization to doxorubicin of TNBC cells, and suggest that targeting Pi levels at local sites might represent the rationale for developing effective and inexpensive strategies for improving triple-negative breast cancer therapy. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Exploring the Oxidation of Lignin-Derived Phenols by a Library of Laccase Mutants
Molecules 2015, 20(9), 15929-15943; doi:10.3390/molecules200915929
Received: 15 July 2015 / Revised: 18 August 2015 / Accepted: 26 August 2015 / Published: 2 September 2015
Cited by 3 | PDF Full-text (1092 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Saturation mutagenesis was performed over six residues delimiting the substrate binding pocket of a fungal laccase previously engineered in the lab. Mutant libraries were screened using sinapic acid as a model substrate, and those mutants presenting increased activity were selected for exploring the
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Saturation mutagenesis was performed over six residues delimiting the substrate binding pocket of a fungal laccase previously engineered in the lab. Mutant libraries were screened using sinapic acid as a model substrate, and those mutants presenting increased activity were selected for exploring the oxidation of lignin-derived phenols. The latter comprised a battery of phenolic compounds of interest due to their use as redox mediators or precursors of added-value products and their biological activity. The new laccase variants were investigated in a multi-screening assay and the structural determinants, at both the substrate and the protein level, for the oxidation of the different phenols are discussed. Laccase activity greatly varied only by changing one or two residues of the enzyme pocket. Our results suggest that once the redox potential threshold is surpassed, the contribution of the residues of the enzymatic pocket for substrate recognition and binding strongly influence the overall rate of the catalytic reaction. Full article
(This article belongs to the Special Issue Biocatalytic Lignin Modification)
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Open AccessArticle Synthetic Routes to N-9 Alkylated 8-Oxoguanines; Weak Inhibitors of the Human DNA Glycosylase OGG1
Molecules 2015, 20(9), 15944-15965; doi:10.3390/molecules200915944
Received: 2 June 2015 / Revised: 22 July 2015 / Accepted: 26 August 2015 / Published: 2 September 2015
Cited by 1 | PDF Full-text (858 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The human 8-oxoguanine DNA glycosylase OGG1 is involved in base excision repair (BER), one of several DNA repair mechanisms that may counteract the effects of chemo- and radiation therapy for the treatment of cancer. We envisage that potent inhibitors of OGG1 may be
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The human 8-oxoguanine DNA glycosylase OGG1 is involved in base excision repair (BER), one of several DNA repair mechanisms that may counteract the effects of chemo- and radiation therapy for the treatment of cancer. We envisage that potent inhibitors of OGG1 may be found among the 9-alkyl-8-oxoguanines. Thus we explored synthetic routes to 8-oxoguanines and examined these as OGG1 inhibitors. The best reaction sequence started from 6-chloroguanine and involved N-9 alkylation, C-8 bromination, and finally simultaneous hydrolysis of both halides. Bromination before N-alkylation should only be considered when the N-substituent is not compatible with bromination conditions. The 8-oxoguanines were found to be weak inhibitors of OGG1. 6-Chloro-8-oxopurines, byproducts in the hydrolysis of 2,6-halopurines, turned out to be slightly better inhibitors than the corresponding 8-oxoguanines. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Concise Synthesis of Broussonone A
Molecules 2015, 20(9), 15966-15975; doi:10.3390/molecules200915966
Received: 3 August 2015 / Revised: 22 August 2015 / Accepted: 25 August 2015 / Published: 2 September 2015
Cited by 2 | PDF Full-text (739 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A concise and expeditious approach to the total synthesis of broussonone A, a p-quinol natural compound, has been developed. The key features of the synthesis include the Grubbs II catalyst mediated cross metathesis of two aromatic subunits, and a chemoselective oxidative dearomatizationin
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A concise and expeditious approach to the total synthesis of broussonone A, a p-quinol natural compound, has been developed. The key features of the synthesis include the Grubbs II catalyst mediated cross metathesis of two aromatic subunits, and a chemoselective oxidative dearomatizationin the presence of two phenol moieties. Especially, optimization associated with the CM reaction of ortho-alkoxystyrenes was also studied, which are known to be ineffective for Ru-catalyzed metathesis reactions under conventional reaction conditions because ortho-alkoxy group could coordinate to the ruthenium center, resulting in the potential complication of catalyst inhibition. Full article
(This article belongs to the Special Issue Natural Product Synthesis: A Platform for Discovery)
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Open AccessArticle Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors
Molecules 2015, 20(9), 15976-15988; doi:10.3390/molecules200915976
Received: 22 May 2015 / Revised: 14 August 2015 / Accepted: 24 August 2015 / Published: 2 September 2015
Cited by 3 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three series of 4,6-dimethoxy-, 4,6-dipiperidino- and 4,6-dimorpholino-1,3,5-triazin-2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline,
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Three series of 4,6-dimethoxy-, 4,6-dipiperidino- and 4,6-dimorpholino-1,3,5-triazin-2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Antioxidant and Anti-Inflammatory Activities of a Natural Compound, Shizukahenriol, through Nrf2 Activation
Molecules 2015, 20(9), 15989-16003; doi:10.3390/molecules200915989
Received: 16 July 2015 / Revised: 18 August 2015 / Accepted: 28 August 2015 / Published: 2 September 2015
Cited by 5 | PDF Full-text (2004 KB) | HTML Full-text | XML Full-text
Abstract
Imbalance in the antioxidant defense system leads to detrimental consequences, such as neurological disorders. The Nrf2 signaling is known as a main pathway involved in cellular defense system. Nrf2 is a transcription factor that regulates oxidative stress response by inducing expression of various
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Imbalance in the antioxidant defense system leads to detrimental consequences, such as neurological disorders. The Nrf2 signaling is known as a main pathway involved in cellular defense system. Nrf2 is a transcription factor that regulates oxidative stress response by inducing expression of various antioxidant enzyme genes. In this study, we screened several pure natural compounds for Nrf2 activator. Among them, shizukahenriol (SZH), isolated from Chloranthus henryi, activated Nrf2, and induced expression of the Nrf2-dependent antioxidant enzymes HO-1, GCLC, and GCLM in BV-2 microglial cells. This natural compound was also effective in suppressing production of inflammatory molecules NO, TNF-α, and inhibition of NF-κB p65 translocation to the nucleus in a dose-dependent manner. We also examined whether SZH rescued the microglial cells from oxidative stress-induced cell death. Pretreatment with SZH dose-dependently attenuated H2O2-induced cytotoxicity in BV-2 microglial cells. These results suggested SZH as a potential neuroprotective agent for neurological disorders. Full article
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Open AccessArticle Adsorption and Corrosion Inhibition Studies of Some Selected Dyes as Corrosion Inhibitors for Mild Steel in Acidic Medium: Gravimetric, Electrochemical, Quantum Chemical Studies and Synergistic Effect with Iodide Ions
Molecules 2015, 20(9), 16004-16029; doi:10.3390/molecules200916004
Received: 2 August 2015 / Revised: 28 August 2015 / Accepted: 28 August 2015 / Published: 2 September 2015
Cited by 13 | PDF Full-text (4403 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The corrosion inhibition properties of some organic dyes, namely Sunset Yellow (SS), Amaranth (AM), Allura Red (AR), Tartrazine (TZ) and Fast Green (FG), for mild steel corrosion in 0.5 M HCl solution, were investigated using gravimetric, potentiodynamic polarization techniques and quantum chemical calculations.
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The corrosion inhibition properties of some organic dyes, namely Sunset Yellow (SS), Amaranth (AM), Allura Red (AR), Tartrazine (TZ) and Fast Green (FG), for mild steel corrosion in 0.5 M HCl solution, were investigated using gravimetric, potentiodynamic polarization techniques and quantum chemical calculations. The results showed that the studied dyes are good corrosion inhibitors with enhanced inhibition efficiencies. The inhibition efficiency of all the studied dyes increases with increase in concentration, and decreases with increase in temperature. The results showed that the inhibition efficiency of the dyes increases in the presence of KI due to synergistic interactions of the dye molecules with iodide (I) ions. Potentiodynamic polarization results revealed that the studied dyes are mixed-type inhibitors both in the absence and presence of KI. The adsorption of the studied dyes on mild steel surface, with and without KI, obeys the Langmuir adsorption isotherm and involves physical adsorption mechanism. Quantum chemical calculations revealed that the most likely sites in the dye molecules for interactions with mild steel are the S, O, and N heteroatoms. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region
Molecules 2015, 20(9), 16030-16047; doi:10.3390/molecules200916030
Received: 30 July 2015 / Revised: 25 August 2015 / Accepted: 29 August 2015 / Published: 2 September 2015
Cited by 3 | PDF Full-text (1043 KB) | HTML Full-text | XML Full-text
Abstract
Background: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization
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Background: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization of a set of aptamers targeting the cis-acting replication element (CRE) of the HCV genome, an essential partner for viral replication and also involved in the regulation of protein synthesis. Methods: Forty-four aptamers were tested for their ability to interfere with viral RNA synthesis in a subgenomic replicon system. Some of the most efficient inhibitors were further evaluated for their potential to affect the recruitment of the HCV RNA-dependent RNA polymerase (NS5B) and the viral translation in cell culture. Results: Four aptamers emerged as potent inhibitors of HCV replication by direct interaction with functional RNA domains of the CRE, yielding a decrease in the HCV RNA levels higher than 90%. Concomitantly, one of them also induced a significant increase in viral translation (>50%). The three remaining aptamers efficiently competed with the binding of the NS5B protein to the CRE. Conclusions: Present findings confirm the potential of the CRE as an anti-HCV target and support the use of aptamers as molecular tools for investigating the functionality of RNA domains in viral genomes. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
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Open AccessArticle Synthesis of Novel 2,5-Disubstituted-1,3,4-thiadiazoles Clubbed 1,2,4-Triazole, 1,3,4-Thiadiazole, 1,3,4-Oxadiazole and/or Schiff Base as Potential Antimicrobial and Antiproliferative Agents
Molecules 2015, 20(9), 16048-16067; doi:10.3390/molecules200916048
Received: 9 August 2015 / Revised: 19 August 2015 / Accepted: 25 August 2015 / Published: 2 September 2015
Cited by 10 | PDF Full-text (756 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some
[...] Read more.
In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some of the synthesized derivatives have displayed promising biological activity. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Comparing the Antibacterial and Functional Properties of Cameroonian and Manuka Honeys for Potential Wound Healing—Have We Come Full Cycle in Dealing with Antibiotic Resistance?
Molecules 2015, 20(9), 16068-16084; doi:10.3390/molecules200916068
Received: 2 July 2015 / Revised: 28 August 2015 / Accepted: 31 August 2015 / Published: 2 September 2015
Cited by 5 | PDF Full-text (1127 KB) | HTML Full-text | XML Full-text
Abstract
The increased incidence of bacterial resistance to antibiotics has generated renewed interest in “traditional” antimicrobials, such as honey. This paper reports on a study comparing physico-chemical, antioxidant and antibacterial characteristics (that potentially contribute in part, to the functional wound healing activity) of Cameroonian
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The increased incidence of bacterial resistance to antibiotics has generated renewed interest in “traditional” antimicrobials, such as honey. This paper reports on a study comparing physico-chemical, antioxidant and antibacterial characteristics (that potentially contribute in part, to the functional wound healing activity) of Cameroonian honeys with those of Manuka honey. Agar well diffusion was used to generate zones of inhibition against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus while broth dilutions were used to study the minimum inhibitory concentrations (MICs). Non-peroxide activity was investigated by catalase for hydrogen peroxide reduction. The Cameroonian honeys demonstrated functional properties similar to Manuka honey, with strong correlations between the antioxidant activity and total phenol content of each honey. They were also as effective as Manuka honey in reducing bacteria load with an MIC of 10% w/v against all three bacteria and exhibited non-peroxide antimicrobial activity. These Cameroon honeys have potential therapeutic activity and may contain compounds with activity against Gram positive and Gram negative bacteria. Antibacterial agents from such natural sources present a potential affordable treatment of wound infections caused by antibiotic resistant bacteria, which are a leading cause of amputations and deaths in many African countries. Full article
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Open AccessArticle N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol
Molecules 2015, 20(9), 16085-16102; doi:10.3390/molecules200916085
Received: 28 July 2015 / Revised: 27 August 2015 / Accepted: 28 August 2015 / Published: 3 September 2015
Cited by 4 | PDF Full-text (1237 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on
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Resveratrol is a natural polyphenol with many interesting biological activities. Its pharmacological exploitation in vivo is, however, hindered by its rapid elimination via phase II conjugative metabolism at the intestinal and, most importantly, hepatic levels. One approach to bypass this problem relies on prodrugs. We report here the synthesis, characterization, hydrolysis, and in vivo pharmacokinetic behavior of resveratrol prodrugs in which the OH groups are engaged in an N-monosubstituted carbamate ester linkage. As promoiety, methoxy-oligo(ethylene glycol) groups (m-OEG) (CH3–[OCH2CH2]n–) of defined chain length (n = 3, 4, 6) were used. These are expected to modulate the chemico-physical properties of the resulting derivatives, much like longer poly(ethylene glycol) (PEG) chains, while retaining a relatively low MW and, thus, a favorable drug loading capacity. Intragastric administration to rats resulted in the appearance in the bloodstream of the prodrug and of the products of its partial hydrolysis, confirming protection from first-pass metabolism during absorption. Full article
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Open AccessArticle An Expedient Regio- and Diastereoselective Synthesis of Hybrid Frameworks with Embedded Spiro[9,10]dihydroanthracene [9,3′]-pyrrolidine and Spiro[oxindole-3,2′-pyrrolidine] Motifs via an Ionic Liquid-Mediated Multicomponent Reaction
Molecules 2015, 20(9), 16142-16153; doi:10.3390/molecules200916142
Received: 8 August 2015 / Revised: 21 August 2015 / Accepted: 24 August 2015 / Published: 3 September 2015
Cited by 4 | PDF Full-text (908 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen-9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic
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A series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen-9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic liquid. This reaction proceeded regio- and diastereoselectively, in good to excellent yields. Full article
(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)
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Open AccessArticle In Silico Identification and in Vitro Activity of Novel Natural Inhibitors of Trypanosoma brucei Glyceraldehyde-3-phosphate-dehydrogenase
Molecules 2015, 20(9), 16154-16169; doi:10.3390/molecules200916154
Received: 9 July 2015 / Revised: 19 August 2015 / Accepted: 27 August 2015 / Published: 3 September 2015
Cited by 4 | PDF Full-text (1689 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP) databases against a multitude of protozoan parasite proteins. Within this project, we screened a
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As part of our ongoing efforts to identify natural products with activity against pathogens causing neglected tropical diseases, we are currently performing an extensive screening of natural product (NP) databases against a multitude of protozoan parasite proteins. Within this project, we screened a database of NPs from a commercial supplier, AnalytiCon Discovery (Potsdam, Germany), against Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH), a glycolytic enzyme whose inhibition deprives the parasite of energy supply. NPs acting as potential inhibitors of the mentioned enzyme were identified using a pharmacophore-based virtual screening and subsequent docking of the identified hits into the active site of interest. In a set of 700 structures chosen for the screening, 13 (1.9%) were predicted to possess significant affinity towards the enzyme and were therefore tested in an in vitro enzyme assay using recombinant TbGAPDH. Nine of these in silico hits (69%) showed significant inhibitory activity at 50 µM, of which two geranylated benzophenone derivatives proved to be particularly active with IC50 values below 10 µM. These compounds also showed moderate in vitro activity against T. brucei rhodesiense and may thus represent interesting starting points for further optimization. Full article
Open AccessArticle MS-Based Metabolite Profiling of Aboveground and Root Components of Zingiber mioga and Officinale
Molecules 2015, 20(9), 16170-16185; doi:10.3390/molecules200916170
Received: 6 August 2015 / Revised: 31 August 2015 / Accepted: 1 September 2015 / Published: 3 September 2015
Cited by 6 | PDF Full-text (2053 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and
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Zingiber species are members of the Zingiberaceae family, and are widely used for medicinal and food purposes. In this study aboveground and root parts of Zingiber mioga and Zingiber officinale were subjected to metabolite profiling by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in order to characterize them by species and parts and also to measure bioactivities. Both primary and secondary metabolites showed clear discrimination in the PCA score plot and PLS-DA by species and parts. Tetrahydrocurcumin, diarylheptanoid, 8-gingerol, and 8-paradol were discriminating metabolites between Z. mioga and Z. officinale that were present in different quantities. Eleven flavonoids, six amino acids, six organic acids, four fatty acids, and gingerenone A were higher in the aboveground parts than the root parts. Antioxidant activities were measured and were highest in the root part of Z. officinale. The relatively high contents of tetrahydrocurcumin, diarylheptanoid, and galanganol C in the root part of Z. officinale showed highly positive correlation with bioactivities based on correlation assay. On the basis of these results, we can suggest different usages of structurally different parts of Zingiber species as food plants. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis, Biological Evaluation and Molecular Docking Studies of Piperidinylpiperidines and Spirochromanones Possessing Quinoline Moieties as Acetyl-CoA Carboxylase Inhibitors
Molecules 2015, 20(9), 16221-16234; doi:10.3390/molecules200916221
Received: 11 August 2015 / Revised: 30 August 2015 / Accepted: 1 September 2015 / Published: 7 September 2015
Cited by 2 | PDF Full-text (1371 KB) | HTML Full-text | XML Full-text
Abstract
Acetyl-coenzyme A carboxylases (ACCs) play critical roles in the regulation of fatty acid metabolism and have been targeted for the development of drugs against obesity, diabetes and other metabolic diseases. Two series of compounds possessing quinoline moieties were designed, synthesized and evaluated for
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Acetyl-coenzyme A carboxylases (ACCs) play critical roles in the regulation of fatty acid metabolism and have been targeted for the development of drugs against obesity, diabetes and other metabolic diseases. Two series of compounds possessing quinoline moieties were designed, synthesized and evaluated for their potential to inhibit acetyl-CoA carboxylases. Most compounds showed moderate to good ACC inhibitory activities and compound 7a possessed the most potent biological activities against ACC1 and ACC2, with IC50 values of 189 nM and 172 nM, respectively, comparable to the positive control. Docking simulation was performed to position compound 7a into the active site of ACC to determine a probable binding model. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Novel Steroidal Glycosides from the Bulbs of Lilium pumilum
Molecules 2015, 20(9), 16255-16265; doi:10.3390/molecules200916255
Received: 25 June 2015 / Revised: 25 August 2015 / Accepted: 31 August 2015 / Published: 8 September 2015
Cited by 4 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Examination of the bulbs of Lilium pumilum (Liliaceae) led to the isolation of four novel steroidal glycosides (14) with a 2,3,4-trisubstituted β-d-glucopyranosyl unit. In 1 and 3, the α-L-arabinopyranosyl moiety is linked to C-3 of the inner trisubstituted
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Examination of the bulbs of Lilium pumilum (Liliaceae) led to the isolation of four novel steroidal glycosides (14) with a 2,3,4-trisubstituted β-d-glucopyranosyl unit. In 1 and 3, the α-L-arabinopyranosyl moiety is linked to C-3 of the inner trisubstituted β-D-glucopyranosyl group and is present as an usual 4C1 conformation. In contrast, in 2 and 4, the α-L-arabinopyranosyl moiety, which is attached to C-4 of the inner trisubstituted β-D-glucopyranosyl group, is present as a 1C4 conformation. The structures of the new steroidal glycosides were determined based on the results of spectroscopic analyses, including two-dimensional (2D) NMR data and hydrolysis. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf
Molecules 2015, 20(9), 16266-16277; doi:10.3390/molecules200916266
Received: 7 June 2015 / Revised: 13 July 2015 / Accepted: 27 July 2015 / Published: 8 September 2015
Cited by 2 | PDF Full-text (732 KB) | HTML Full-text | XML Full-text
Abstract
Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL−1. Then, the chemical composition
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Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL−1. Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I) were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis) and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Structure and Antibacterial Activity of Ambobactin, a New Telomycin-Like Cyclic Depsipeptide Antibiotic Produced by Streptomyces ambofaciens F3
Molecules 2015, 20(9), 16278-16289; doi:10.3390/molecules200916278
Received: 8 July 2015 / Revised: 31 August 2015 / Accepted: 2 September 2015 / Published: 9 September 2015
PDF Full-text (855 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new telomycin-like cyclic depsipeptide, ambobactin (1), was isolated from the metabolites of Streptomyces ambofaciens F3, an endophyte of Platycladus orientalis. Its structure was elucidated on the basis of extensive spectroscopic analysis and advanced Marfey’s method. Ambobactin is structurally related
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A new telomycin-like cyclic depsipeptide, ambobactin (1), was isolated from the metabolites of Streptomyces ambofaciens F3, an endophyte of Platycladus orientalis. Its structure was elucidated on the basis of extensive spectroscopic analysis and advanced Marfey’s method. Ambobactin is structurally related with telomycin, except that the configuration of the 3-methyltryptophanes in their structures is different. It exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, this investigation revealed that S. ambofaciens F3 is a new producer of telomycin-like antibiotics. Full article
Open AccessArticle Escherichia coli ASKA Clone Library Harboring tRNA-Specific Adenosine Deaminase (tadA) Reveals Resistance towards Xanthorrhizol
Molecules 2015, 20(9), 16290-16305; doi:10.3390/molecules200916290
Received: 11 June 2015 / Revised: 27 August 2015 / Accepted: 31 August 2015 / Published: 9 September 2015
Cited by 2 | PDF Full-text (1559 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Xanthorrhizol is a potent antimicrobial compound isolated from the rhizome of Curcuma xanthorrhiza. However, the mechanism of xanthorrhizol action is unknown. To screen for probable target(s), we introduced the ASKA pooled-plasmid library into Escherichia coli W3110 imp4213 and enriched the library for
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Xanthorrhizol is a potent antimicrobial compound isolated from the rhizome of Curcuma xanthorrhiza. However, the mechanism of xanthorrhizol action is unknown. To screen for probable target(s), we introduced the ASKA pooled-plasmid library into Escherichia coli W3110 imp4213 and enriched the library for resistant clones with increasing concentrations of xanthorrhizol. After three rounds of enrichment, we found nine genes that increased xanthorrhizol resistance. The resistant clones were able to grow in LB medium containing 256 µg/mL xanthorrhizol, representing a 16-fold increase in the minimum inhibitory concentration. Subsequent DNA sequence analysis revealed that overexpression of tadA, galU, fucU, ydeA, ydaC, soxS, nrdH, yiiD, and mltF genes conferred increased resistance towards xanthorrhizol. Among these nine genes, tadA is the only essential gene. tadA encodes a tRNA-specific adenosine deaminase. Overexpression of E. coli W3110 imp4213 (pCA24N-tadA) conferred resistance to xanthorrhizol up to 128 µg/mL. Moreover, overexpression of two tadA mutant enzymes (A143V and F149G) led to a twofold increase in the MIC. These results suggest that the targets of xanthorrhizol may include tadA, which has never before been explored as an antibiotic target. Full article
Open AccessArticle Enzymatic Transesterification of Kraft Lignin with Long Acyl Chains in Ionic Liquids
Molecules 2015, 20(9), 16334-16353; doi:10.3390/molecules200916334
Received: 7 July 2015 / Revised: 31 August 2015 / Accepted: 2 September 2015 / Published: 9 September 2015
Cited by 3 | PDF Full-text (3055 KB) | HTML Full-text | XML Full-text
Abstract
Valorization of lignin is essential for the economic viability of the biorefinery concept. For example, the enhancement of lignin hydrophobicity by chemical esterification is known to improve its miscibility in apolar polyolefin matrices, thereby helping the production of bio-based composites. To this end
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Valorization of lignin is essential for the economic viability of the biorefinery concept. For example, the enhancement of lignin hydrophobicity by chemical esterification is known to improve its miscibility in apolar polyolefin matrices, thereby helping the production of bio-based composites. To this end and due to its many reactive hydroxyl groups, lignin is a challenging macromolecular substrate for biocatalyzed esterification in non-conventional media. The present work describes for the first time the lipase-catalyzed transesterification of Kraft lignin in ionic liquids (ILs). Three lipases, three 1-butyl-3-methylimidazolium based ILs and ethyl oleate as long chain acyl donor were selected. Best results were obtained with a hydrophilic/hydrophobic binary IL system (1-butyl-3-methylimidazolium trifluoromethanesulfonate/1-butyl-3-methylimidazolium hexafluoro- phosphate, 1/1 v/v) and the immobilized lipase B from Candida antarctica (CALB) that afforded a promising transesterification yield (ca. 30%). Similar performances were achieved by using 1-butyl-3-methylimidazolium hexafluorophosphate as a coating agent for CALB rather than as a co-solvent in 1-butyl-3-methylimidazolium trifluoromethane-sulfonate thus limiting the use of hydrophobic IL. Structural characterization of lignin oleate was performed by spectroscopic studies (FTIR and 1H-NMR). The synthesized lignin oleate exhibited interesting thermal and textural properties, different from those of the original Kraft lignin. Full article
(This article belongs to the Special Issue Biocatalytic Lignin Modification)
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Open AccessArticle Synthesis and Pharmacochemistry of New Pleiotropic Pyrrolyl Derivatives
Molecules 2015, 20(9), 16354-16374; doi:10.3390/molecules200916354
Received: 14 July 2015 / Revised: 2 September 2015 / Accepted: 3 September 2015 / Published: 10 September 2015
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Abstract
Within the framework of our attempts to synthesize pleiotropic anti-inflammatory agents, we have synthesized some chalcones and their corresponding 3,4-pyrrolyl derivatives. Chalcones constitute a class of compounds with high biological impact. They are known for a number of biological activities, including anti-inflammatory and
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Within the framework of our attempts to synthesize pleiotropic anti-inflammatory agents, we have synthesized some chalcones and their corresponding 3,4-pyrrolyl derivatives. Chalcones constitute a class of compounds with high biological impact. They are known for a number of biological activities, including anti-inflammatory and free radical scavenging activities. They inhibit several enzymes implicated in the inflammatory process, such as lipoxygenase, cyclooxygenase (COX) and lysozymes. The synthesized pyrroles have been studied for: (1) their in vitro inhibition of lipoxygenase; (2) their in vitro inhibition of COX; (3) their in vitro inhibition of lipid peroxidation; (4) their interaction with the stable, N-centered, free radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH); (5) their inhibition on interleukin-6 (IL-6); (6) their anti-proteolytic activity; and (7) their in vivo anti-inflammatory activity using carrageenan-induced rat paw edema. Their physicochemical properties were determined to explain the biological results. Lipophilicity was experimentally determined. 2i and 2v were found to be promising multifunctional molecules with high antiproteolytic and anti-inflammatory activities in combination with anti-interleukin-6 activity. Full article
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Open AccessArticle Separation and Identification of Four New Compounds with Antibacterial Activity from Portulaca oleracea L.
Molecules 2015, 20(9), 16375-16387; doi:10.3390/molecules200916375
Received: 21 July 2015 / Revised: 14 August 2015 / Accepted: 28 August 2015 / Published: 10 September 2015
Cited by 6 | PDF Full-text (737 KB) | HTML Full-text | XML Full-text
Abstract
The Portulaca oleracea L. (P. oleracea) has been used to treat bacillary dysentery for thousands of years in China. Pharmacology studies on P. oleracea have also showed its significant antibacterial effects on the enteropathogenic bacteria, which might reveal the
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The Portulaca oleracea L. (P. oleracea) has been used to treat bacillary dysentery for thousands of years in China. Pharmacology studies on P. oleracea have also showed its significant antibacterial effects on the enteropathogenic bacteria, which might reveal the treatment of P. oleracea in cases of bacillary dysentery to some extent. To date, however, the therapeutic basis of P. oleracea treating on bacillary dysentery remains unknown. We determined the antibacterial effective fraction of P. oleracea in a previous study. The current study, which is based on our previous study, was first designed to isolate, identify and screen antibacterial active constituents from P. oleracea. As a result, four new compounds (14), portulacerebroside B (1), portulacerebroside C (2), portulacerebroside D (3) and portulaceramide A (4) along with five known compounds (59) were isolated, and structures were established by their physico-chemical constants and spectroscopic analysis. The antibacterial activities against common enteropathogenic bacteria were evaluated for all compounds and the new compounds 14 showed significant antibacterial effect on enteropathogenic bacteria in vitro, which might contribute to revealing the treatment of P. oleracea in cases of bacillary dysentery. Full article
Open AccessArticle Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells
Molecules 2015, 20(9), 16388-16403; doi:10.3390/molecules200916388
Received: 5 August 2015 / Revised: 1 September 2015 / Accepted: 1 September 2015 / Published: 10 September 2015
Cited by 5 | PDF Full-text (1007 KB) | HTML Full-text | XML Full-text
Abstract
Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is
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Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR
Molecules 2015, 20(9), 16404-16418; doi:10.3390/molecules200916404
Received: 9 July 2015 / Revised: 30 August 2015 / Accepted: 2 September 2015 / Published: 10 September 2015
Cited by 8 | PDF Full-text (2273 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a
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We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64. Full article
(This article belongs to the collection Poorly Soluble Drugs)
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Open AccessArticle Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives
Molecules 2015, 20(9), 16419-16434; doi:10.3390/molecules200916419
Received: 4 August 2015 / Revised: 1 September 2015 / Accepted: 3 September 2015 / Published: 10 September 2015
Cited by 4 | PDF Full-text (630 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino)-5H-thiazolo[3,2-a]pyrimidin-5-ones
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A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino)-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and Evaluation of a Rationally Designed Click-Based Library for G-Quadruplex Selective DNA Photocleavage
Molecules 2015, 20(9), 16446-16465; doi:10.3390/molecules200916446
Received: 24 July 2015 / Revised: 22 August 2015 / Accepted: 31 August 2015 / Published: 10 September 2015
PDF Full-text (2299 KB) | HTML Full-text | XML Full-text
Abstract
DNA containing repeating G-rich sequences can adopt higher-order structures known as G-quadruplexes (G4). These structures are believed to form within telomeres and the promoter regions of some genes, particularly in a number of proto-oncogenes, where they may play a role in regulating transcription.
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DNA containing repeating G-rich sequences can adopt higher-order structures known as G-quadruplexes (G4). These structures are believed to form within telomeres and the promoter regions of some genes, particularly in a number of proto-oncogenes, where they may play a role in regulating transcription. Alternatively, G4 DNA may act as a barrier to replication. To investigate these potential biological roles, probes that combine highly selective G4 DNA targeting with photocleavage activity can allow temporal detection of G4 DNA, providing opportunities to obtain novel insights about the biological roles of G4 DNA. We have designed, synthesized, and screened a small library of potential selective G-quadruplex DNA photocleavage agents incorporating the G-quadruplex targeting moiety of 360A with known photocleavage groups linked via “click” chemistry. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Identification of Cultured and Natural Astragalus Root Based on Monosaccharide Mapping
Molecules 2015, 20(9), 16466-16490; doi:10.3390/molecules200916466
Received: 9 August 2015 / Revised: 1 September 2015 / Accepted: 3 September 2015 / Published: 11 September 2015
Cited by 1 | PDF Full-text (1921 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As the main substances responsible for immunomodulatory activity, saccharides can be used as quality indicators for Astragalus root (RA). Saccharide content is commonly determined by ultraviolet spectroscopy, which lacks species specificity and has not been applied in the Chinese Pharmacopoeia. Monosaccharide mapping based
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As the main substances responsible for immunomodulatory activity, saccharides can be used as quality indicators for Astragalus root (RA). Saccharide content is commonly determined by ultraviolet spectroscopy, which lacks species specificity and has not been applied in the Chinese Pharmacopoeia. Monosaccharide mapping based on trifluoroacetic acid (TFA) hydrolysis can be used for quantitative analysis of saccharide compositions. In addition, species specificity can be evaluated by analysis of the mapping characteristics. In this study, monosaccharide mapping of soluble saccharides in the cytoplasm and polysaccharides in the cell wall of 24 batches of RA samples with different growth patterns were obtained based on TFA hydrolysis followed by gas chromatography-mass spectrometry. Results indicated that the mapping and the molar ratios of saccharide compositions of the cultured and natural RA samples were different for both cytoplasm and cell wall. For example, the molar ratio of mannose and arabinose was more than 3.5:1 in cytoplasm in cultured RA, whereas the ratio was less than 3.5:1 in natural RA. This research not only lays a foundation for screening indicators for RA, but also provided new ways of evaluating the quality of Chinese medicinal materials in which saccharides are the main bioactive substances. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Spectroscopic Study on the Interaction between Naphthalimide-Polyamine Conjugates and Bovine Serum Albumin (BSA)
Molecules 2015, 20(9), 16491-16523; doi:10.3390/molecules200916491
Received: 13 July 2015 / Revised: 14 August 2015 / Accepted: 14 August 2015 / Published: 11 September 2015
Cited by 9 | PDF Full-text (1808 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The effect of a naphthalimide pharmacophore coupled with diverse substituents on the interaction between naphthalimide-polyamine conjugates 14 and bovine serum albumin (BSA) was studied by UV absorption, fluorescence and circular dichroism (CD) spectroscopy under physiological conditions (pH = 7.4). The observed
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The effect of a naphthalimide pharmacophore coupled with diverse substituents on the interaction between naphthalimide-polyamine conjugates 14 and bovine serum albumin (BSA) was studied by UV absorption, fluorescence and circular dichroism (CD) spectroscopy under physiological conditions (pH = 7.4). The observed spectral quenching of BSA by the compounds indicated that they could bind to BSA. Furthermore, caloric fluorescent tests revealed that the quenching mechanisms of compounds 13 were basically static type, but that of compound 4 was closer to a classical type. The Ksv values at room temperature for compound-BSA complexes-1-BSA, 2-BSA, 3-BSA and 4-BSA were 1.438 × 104, 3.190 × 104, 5.700 × 104 and 4.745 × 105, respectively, compared with the value of MINS, 2.863 × 104 at Ex = 280 nm. The obtained quenching constant, binding constant and thermodynamic parameter suggested that the binding between compounds 14 with BSA protein, significantly affected by the substituted groups on the naphthalene backbone, was formed by hydrogen bonds, and other principle forces mainly consisting of charged and hydrophobic interactions. Based on results from the analysis of synchronous three-dimensional fluorescence and CD spectra, we can conclude that the interaction between compounds 14 and BSA protein has little impact on the BSA conformation. Calculated results obtained from in silico molecular simulation showed that compound 1 did not prefer either enzymatic drug sites I or II over the other. However, DSII in BSA was more beneficial than DSI for the binding between compounds 24 and BSA protein. The binding between compounds 13 and BSA was hydrophobic in nature, compared with the electrostatic interaction between compound 4 and BSA. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Beneficial Effects of Ethanolic and Hexanic Rice Bran Extract on Mitochondrial Function in PC12 Cells and the Search for Bioactive Components
Molecules 2015, 20(9), 16524-16539; doi:10.3390/molecules200916524
Received: 14 July 2015 / Revised: 3 September 2015 / Accepted: 7 September 2015 / Published: 11 September 2015
Cited by 3 | PDF Full-text (2334 KB) | HTML Full-text | XML Full-text
Abstract
Mitochondria are involved in the aging processes that ultimately lead to neurodegeneration and the development of Alzheimer’s disease (AD). A healthy lifestyle, including a diet rich in antioxidants and polyphenols, represents one strategy to protect the brain and to prevent neurodegeneration. We recently
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Mitochondria are involved in the aging processes that ultimately lead to neurodegeneration and the development of Alzheimer’s disease (AD). A healthy lifestyle, including a diet rich in antioxidants and polyphenols, represents one strategy to protect the brain and to prevent neurodegeneration. We recently reported that a stabilized hexanic rice bran extract (RBE) rich in vitamin E and polyphenols (but unsuitable for human consumption) has beneficial effects on mitochondrial function in vitro and in vivo (doi:10.1016/j.phrs.2013.06.008, 10.3233/JAD-132084). To enable the use of RBE as food additive, a stabilized ethanolic extract has been produced. Here, we compare the vitamin E profiles of both extracts and their effects on mitochondrial function (ATP concentrations, mitochondrial membrane potential, mitochondrial respiration and mitochondrial biogenesis) in PC12 cells. We found that vitamin E contents and the effects of both RBE on mitochondrial function were similar. Furthermore, we aimed to identify components responsible for the mitochondria-protective effects of RBE, but could not achieve a conclusive result. α-Tocotrienol and possibly also γ-tocotrienol, α-tocopherol and δ-tocopherol might be involved, but hitherto unknown components of RBE or a synergistic effect of various components might also play a role in mediating RBE’s beneficial effects on mitochondrial function. Full article
Open AccessArticle Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities
Molecules 2015, 20(9), 16566-16581; doi:10.3390/molecules200916566
Received: 21 July 2015 / Revised: 14 August 2015 / Accepted: 17 August 2015 / Published: 11 September 2015
Cited by 3 | PDF Full-text (1772 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of five new 2‐(1‐benzofuran‐2‐yl)‐2‐oxoethyl 4-(un/substituted)benzoates 4(ae), with the general formula of C8H5O(C=O)CH2O(C=O)C6H4X, X = H, Cl, CH3, OCH3 or NO2, was
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A series of five new 2‐(1‐benzofuran‐2‐yl)‐2‐oxoethyl 4-(un/substituted)benzoates 4(ae), with the general formula of C8H5O(C=O)CH2O(C=O)C6H4X, X = H, Cl, CH3, OCH3 or NO2, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(ae) were characterized by FTIR, 1H-, 13C- and 1H-13C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Cold-Setting Inkjet Printed Titania Patterns Reinforced by Organosilicate Binder
Molecules 2015, 20(9), 16582-16603; doi:10.3390/molecules200916582
Received: 8 June 2015 / Revised: 20 August 2015 / Accepted: 24 August 2015 / Published: 11 September 2015
Cited by 3 | PDF Full-text (1429 KB) | HTML Full-text | XML Full-text
Abstract
A hybrid organo-silica sol was used as a binder for reinforcing of commercial titanium dioxide nanoparticles (Evonic P25) deposited on glass substrates. The organo-silica binder was prepared by the sol-gel process and mixtures of titania nanoparticles with the binder in various ratios were
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A hybrid organo-silica sol was used as a binder for reinforcing of commercial titanium dioxide nanoparticles (Evonic P25) deposited on glass substrates. The organo-silica binder was prepared by the sol-gel process and mixtures of titania nanoparticles with the binder in various ratios were deposited by materials printing technique. Patterns with both positive and negative features down to 100 µm size and variable thickness were reliably printed by Fujifilm Dimatix inkjet printer. All prepared films well adhered onto substrates, however further post-printing treatment proved to be necessary in order to improve their reactivity. The influence of UV radiation as well as of thermal sintering on the final electrochemical and photocatalytic properties was investigated. A mixture containing 63 wt % of titania delivered a balanced compromise of mechanical stability, generated photocurrent density and photocatalytic activity. Although the heat treated samples yielded generally higher photocurrent, higher photocatalytic activity towards model aqueous pollutant was observed in the case of UV cured samples because of their superhydrophilic properties. While heat sintering remains the superior processing method for inorganic substrates, UV-curing provides a sound treatment option for heat sensitive ones. Full article
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Open AccessArticle Design, Synthesis and Biological Evaluation of Novel Substituted N,N′-Diaryl ureas as Potent p38 Inhibitors
Molecules 2015, 20(9), 16604-16619; doi:10.3390/molecules200916604
Received: 26 August 2015 / Revised: 7 September 2015 / Accepted: 9 September 2015 / Published: 11 September 2015
Cited by 1 | PDF Full-text (1255 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of substituted N,N′-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation
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A novel series of substituted N,N′-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation indicated that most compounds possessed good p38α inhibitory potencies. Among these compounds, 9g appeared to be the most powerful and is the main compound that we will study in the future. Full article
(This article belongs to the Special Issue Kinase Inhibitor Chemistry)
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Open AccessArticle Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents
Molecules 2015, 20(9), 16620-16642; doi:10.3390/molecules200916620
Received: 26 June 2015 / Revised: 18 August 2015 / Accepted: 20 August 2015 / Published: 14 September 2015
Cited by 5 | PDF Full-text (1734 KB) | HTML Full-text | XML Full-text
Abstract
Sixteen new phthalimide derivatives were synthesized and evaluated for their in vitro anti-microbial, anti-oxidant and anti-inflammatory activities. The cytotoxicity for all synthesized compounds was also determined in cancer cell lines and in normal human cells. None of the target derivatives had any cytotoxic
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Sixteen new phthalimide derivatives were synthesized and evaluated for their in vitro anti-microbial, anti-oxidant and anti-inflammatory activities. The cytotoxicity for all synthesized compounds was also determined in cancer cell lines and in normal human cells. None of the target derivatives had any cytotoxic activity. (ZE)-2-[4-(1-Hydrazono-ethyl) phenyl]isoindoline-1,3-dione (12) showed remarkable anti-microbial activity. Its activity against Bacillus subtilis was 133%, 106% and 88.8% when compared with the standard antibiotics ampicillin, cefotaxime and gentamicin, respectively. Compound 12 also showed its highest activities in Gram negative bacteria against Pseudomonas aeruginosa where the percentage activities were 75% and 57.6% when compared sequentially with the standard antibiotics cefotaxime and gentamicin. It was also found that the compounds 2-[4-(4-ethyl-3-methyl-5-thioxo-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13b) and 2-[4-(3-methyl-5-thioxo-4-phenyl-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13c) had anti-oxidant activity. 4-(N'-{1-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenyl]-ethylidene}-hydrazino)-benzenesulfonamide (17c) showed the highest in vitro anti-inflammatory activity of the tested compounds (a decrease of 32%). To determine the mechanism of the anti-inflammatory activity of 17c, a docking study was carried out on the COX-2 enzyme. The results confirmed that 17c had a higher binding energy score (−17.89 kcal/mol) than that of the ligand celecoxib (−17.27 kcal/mol). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Quantification of CH-π Interactions Using Calix[4]pyrrole Receptors as Model Systems
Molecules 2015, 20(9), 16672-16686; doi:10.3390/molecules200916672
Received: 7 August 2015 / Revised: 1 September 2015 / Accepted: 7 September 2015 / Published: 14 September 2015
Cited by 6 | PDF Full-text (1931 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We describe the use of two series of aryl-extended calix[4]pyrrole receptors bearing two and four electronically tunable phenyl groups, respectively, in their meso-positions as model systems for the quantification of CH-π interactions in solution. The “four-wall” and the “two-wall” receptors formed thermodynamically
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We describe the use of two series of aryl-extended calix[4]pyrrole receptors bearing two and four electronically tunable phenyl groups, respectively, in their meso-positions as model systems for the quantification of CH-π interactions in solution. The “four-wall” and the “two-wall” receptors formed thermodynamically stable 1:1 complexes in acetonitrile solution with both trimethylamine N-oxide and trimethylphosphine P-oxide as guests. The complexes were mainly stabilized by the formation of four convergent hydrogen bonds between the oxygen atom of the guests and the pyrrole NHs of the host. In general, the N-oxide produced thermodynamically more stable hydrogen bonding interactions than the P-oxide. Upon guest binding, the receptors adopted the cone conformation and the methyl groups of the included guests engaged in CH-π interactions with the aromatic walls. We show that the modification of the electronic properties of the aromatic surfaces, in any of the receptor series, did not have a significant impact in the measured binding affinities for a given guest. However, the larger binding affinities determined for the “four-wall” receptors in comparison to the “two-wall” counterparts supported the importance of CH-π interactions on guest complexation. The strength of the CH-π interactions present in the inclusion complexes was quantified employing the octamethyl calix[4]pyrrole as reference. We determined an average magnitude of ~1 kcal·mol−1 for each CH-π interaction. The CH-π interactions featured a reduced electrostatic nature and thus dispersion forces were assigned as main contributors of their strength. Full article
(This article belongs to the Special Issue Noncovalent pi-Interactions)
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Open AccessArticle Characterization of Fatty Acid, Amino Acid and Volatile Compound Compositions and Bioactive Components of Seven Coffee (Coffea robusta) Cultivars Grown in Hainan Province, China
Molecules 2015, 20(9), 16687-16708; doi:10.3390/molecules200916687
Received: 27 July 2015 / Revised: 26 August 2015 / Accepted: 2 September 2015 / Published: 14 September 2015
Cited by 2 | PDF Full-text (1635 KB) | HTML Full-text | XML Full-text
Abstract
Compositions of fatty acid, amino acids, and volatile compound were investigated in green coffee beans of seven cultivars of Coffea robusta grown in Hainan Province, China. The chlorogenic acids, trigonelline, caffeine, total lipid, and total protein contents as well as color parameters were
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Compositions of fatty acid, amino acids, and volatile compound were investigated in green coffee beans of seven cultivars of Coffea robusta grown in Hainan Province, China. The chlorogenic acids, trigonelline, caffeine, total lipid, and total protein contents as well as color parameters were measured. Chemometric techniques, principal component analysis (PCA), hierarchical cluster analysis (HCA), and analysis of one-way variance (ANOVA) were performed on the complete data set to reveal chemical differences among all cultivars and identify markers characteristic of a particular botanical origin of the coffee. The major fatty acids of coffee were linoleic acid, palmitic acid, oleic acid, and arachic acid. Leucine (0.84 g/100 g DW), lysine (0.63 g/100 g DW), and arginine (0.61 g/100 g DW) were the predominant essential amino acids (EAAs) in the coffee samples. Seventy-nine volatile compounds were identified and semi-quantified by HS-SPME/GC-MS. PCA of the complete data matrix demonstrated that there were significant differences among all cultivars, HCA supported the results of PCA and achieved a satisfactory classification performance. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle pH-Dependence of the Aqueous Phase Room Temperature Brønsted Acid-Catalyzed Chemoselective Oxidation of Sulfides with H2O2
Molecules 2015, 20(9), 16709-16722; doi:10.3390/molecules200916709
Received: 13 July 2015 / Revised: 1 September 2015 / Accepted: 2 September 2015 / Published: 14 September 2015
Cited by 2 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A pH-dependence of the Brønsted acid-catalyzed oxidation of sulfides to the corresponding sulfoxides with H2O2is reported for the first time based on our systematic investigation of the catalytic performance of a series of Brønsted acids. For all of the
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A pH-dependence of the Brønsted acid-catalyzed oxidation of sulfides to the corresponding sulfoxides with H2O2 is reported for the first time based on our systematic investigation of the catalytic performance of a series of Brønsted acids. For all of the Brønsted acids investigated, the catalytic performances do not depend on the catalyst loading (mol ratio of Brønsted acid to substrate), but rather depend on the pH value of the aqueous reaction solution. All of them can give more than 98% conversion and selectivity in their aqueous solution at pH 1.30, no matter how much the catalyst loading is and what the Brønsted acid is. This pH-dependence principle is a very novel perspective to understand the Brønsted-acid catalysis system compared with our common understanding of the subject. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Anti-Oxidant, Anti-Aging, and Anti-Melanogenic Properties of the Essential Oils from Two Varieties of Alpinia zerumbet
Molecules 2015, 20(9), 16723-16740; doi:10.3390/molecules200916723
Received: 13 August 2015 / Revised: 3 September 2015 / Accepted: 10 September 2015 / Published: 14 September 2015
Cited by 4 | PDF Full-text (1130 KB) | HTML Full-text | XML Full-text
Abstract
Here, we investigated the anti-oxidant and anti-aging effects of essential oils (EOs) from the leaves of Alpinia zerumbet (tairin and shima) in vitro and anti-melanogenic effects in B16F10 melanoma cells. The anti-oxidant activities were performed with 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium
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Here, we investigated the anti-oxidant and anti-aging effects of essential oils (EOs) from the leaves of Alpinia zerumbet (tairin and shima) in vitro and anti-melanogenic effects in B16F10 melanoma cells. The anti-oxidant activities were performed with 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); nitric oxide; singlet oxygen; hydroxyl radical scavenging; and xanthine oxidase. The inhibitory activities against collagenase, elastase, hyaluronidase, and tyrosinase were employed for anti-aging. The anti-melanogenic was assessed in B16F10 melanoma cells by melanin synthesis and intracellular tyrosinase inhibitory activity. The volatile chemical composition of the essential oil was analyzed with gas chromatography-mass spectrometry (GC/MS). The EO was a complex mixture mainly consisting of monoterpenes and sesquiterpenes. The results revealed that tairin and shima EOs showed strong anti-oxidant activities against DPPH and nitric oxide, hydroxyl radical scavenging activity, and xanthine oxidase inhibition. Compared to shima EO; tairin EO exhibited strong anti-aging activity by inhibiting collagenase, tyrosinase, hyaluronidase, and elastase (IC50 = 11 ± 0.1; 25 ± 1.2; 83 ± 1.6; and 213 ± 2 μg/mL, respectively). Both EOs inhibited intracellular tyrosinase activity; thus, reducing melanin synthesis. These results suggest that tairin EO has better anti-oxidant/anti-aging activity than shima EO, but both are equally anti-melanogenic. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Insecticidal and Nematicidal Activities of Novel Mimosine Derivatives
Molecules 2015, 20(9), 16741-16756; doi:10.3390/molecules200916741
Received: 11 August 2015 / Revised: 4 September 2015 / Accepted: 10 September 2015 / Published: 14 September 2015
Cited by 3 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text
Abstract
Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal
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Mimosine, a non-protein amino acid, is found in several tropical and subtropical plants, which has high value for medicine and agricultural chemicals. Here, in continuation of works aimed to development of natural product-based pesticidal agents, we present the first significant findings for insecticidal and nematicidal activities of novel mimosine derivatives. Interestingly, mimosinol and deuterated mimosinol (D-mimosinol) from mimosine had strong insecticidal activity which could be a result of tyrosinase inhibition (IC50 = 31.4 and 46.1 μM, respectively). Of synthesized phosphoramidothionate derivatives from two these amino alcohols, two compounds (1a and 1b) showed high insecticidal activity (LD50 = 0.5 and 0.7 μg/insect, respectively) with 50%–60% mortality at 50 μg/mL which may be attributed to acetylcholinesterase inhibition. Compounds 1a and 1b also had strong nematicidal activity with IC50 = 31.8 and 50.2 μM, respectively. Our results suggest that the length of the alkyl chain and the functional group at the C5-position of phosphoramidothionates derived from mimosinol and d-mimosinol are essential for the insecticidal and nematicidal activities. These results reveal an unexplored scaffold as new insecticide and nematicide. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Involvement of the Heme-Oxygenase Pathway in the Antiallodynic and Antihyperalgesic Activity of Harpagophytum procumbens in Rats
Molecules 2015, 20(9), 16758-16769; doi:10.3390/molecules200916758
Received: 17 July 2015 / Revised: 26 August 2015 / Accepted: 8 September 2015 / Published: 15 September 2015
Cited by 3 | PDF Full-text (1516 KB) | HTML Full-text | XML Full-text
Abstract
Harpagophytum procumbens (H. procumbens), also known as Devil’s Claw, has been used to treat a wide range of pathological conditions, including pain, arthritis and inflammation. Inflammatory mediators, released at the site of injury, can sensitize nociceptive terminals and are responsible for
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Harpagophytum procumbens (H. procumbens), also known as Devil’s Claw, has been used to treat a wide range of pathological conditions, including pain, arthritis and inflammation. Inflammatory mediators, released at the site of injury, can sensitize nociceptive terminals and are responsible for allodynia and hyperalgesia. Carbon monoxide (CO), produced in a reaction catalyzed by the enzyme heme oxygenase (HO), may play a role in nociceptive processing and has also been recognized to act as a neurotransmitter or neuromodulator in the nervous system. This study was designed to investigate whether the HO/CO pathway is involved in the analgesic response of H. procumbens in carrageenan-induced hyperalgesia in rats. Mechanical allodynia and thermal hyperalgesia were evaluated by using von Frey filaments and the plantar test, respectively. The results of our experiments showed that pretreatment with the HO inhibitor ZnPP IX significantly decreased the antihyperalgesic effect produced by H. procumbens (800 mg/kg, i.p.) in carrageenan-injected rats. Consistently, the pretreatment with hemin, a HO-1 substrate, or CORM-3, a CO releasing molecule, before a low dose of H. procumbens (300 mg/kg, i.p.) induced a clear antiallodynic response in carrageenan injected rats. These results suggest the involvement of HO-1/CO system in the antiallodynic and antihyperalgesic effect of H. procumbens in carrageenan-induced inflammatory pain. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Acetylated Rhamnogalacturonans from Immature Fruits of Abelmoschus esculentus Inhibit the Adhesion of Helicobacter pylori to Human Gastric Cells by Interaction with Outer Membrane Proteins
Molecules 2015, 20(9), 16770-16787; doi:10.3390/molecules200916770
Received: 13 July 2015 / Revised: 3 September 2015 / Accepted: 7 September 2015 / Published: 15 September 2015
Cited by 1 | PDF Full-text (2032 KB) | HTML Full-text | XML Full-text
Abstract
Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus) are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori) to stomach tissue. The present study investigates structural and functional features of polymers responsible for
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Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus) are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori) to stomach tissue. The present study investigates structural and functional features of polymers responsible for this inhibition of bacterial attachment to host cells. Ammonium sulfate precipitation of an aqueous extract yielded two fractions at 60% and 90% saturation with significant antiadhesive effects against H. pylori, strain J99, (FE60% 68% ± 15%; FE90% 75% ± 11% inhibition rates) after preincubation of the bacteria at 1 mg/mL. Sequential extraction of okra fruits yielded hot buffer soluble solids (HBSS) with dose dependent antiadhesive effects against strain J99 and three clinical isolates. Preincubation of H. pylori with HBSS (1 mg/mL) led to reduced binding to 3ʹ-sialyl lactose, sialylated Lea and Lex. A reduction of bacterial binding to ligands complementary to BabA and SabA was observed when bacteria were pretreated with FE90%. Structural analysis of the antiadhesive polysaccharides (molecular weight, monomer composition, linkage analysis, stereochemistry, and acetylation) indicated the presence of acetylated rhamnogalacturonan-I polymers, decorated with short galactose side chains. Deacetylation of HBSS and FE90% resulted in loss of the antiadhesive activity, indicating esterification being a prerequisite for antiadhesive activity. Full article
Open AccessArticle Optimized Extraction of Polysaccharides from Grateloupia livida (Harv.) Yamada and Biological Activities
Molecules 2015, 20(9), 16817-16832; doi:10.3390/molecules200916817
Received: 17 August 2015 / Revised: 7 September 2015 / Accepted: 10 September 2015 / Published: 16 September 2015
Cited by 5 | PDF Full-text (1974 KB) | HTML Full-text | XML Full-text
Abstract
Polysaccharides from Grateloupia livida (Harv.) Yamada (GL) were extracted by a heating circumfluence method. Single-factor experiments were performed for the three parameters: extraction time (X1), extraction temperature (X2) and the ratio of water to raw material (X3)
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Polysaccharides from Grateloupia livida (Harv.) Yamada (GL) were extracted by a heating circumfluence method. Single-factor experiments were performed for the three parameters: extraction time (X1), extraction temperature (X2) and the ratio of water to raw material (X3) and their test range. From preliminary experimental results, one type of the response surface methodology, the Box-Behnken design was applied for the optimizing polysaccharide extraction conditions. The experimental data obtained were fitted to a second-order polynomial equation. The optimal conditions were extraction time 5 h, extraction temperature 100 °C and ratio of water to raw material 70 mL/g. Under these conditions, the experimental yield was 39.22% ± 0.09%, which well matched the predicted value (39.25%), with 0.9774 coefficient of determination (R2). GL polysaccharides had scavenging activities for DPPH and hydroxyl radicals in vitro. The scavenging rates for both radicals peaked at 20 mg/mL GL concentration. However, the positive standard, VC (ascorbic acid), possessed stronger antioxidant activities than GL polysaccharides. Furthermore, the anticancer activity of GL polysaccharides on HepG2 cell proliferation increased dose- and time-dependently, but the positive standard, 5-fluorouracil (5-fu) showed more significant anticancer activity in this study. Overall, GL polysaccharides may have potential applications in the medical and food industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Isolation and Functional Characterization of a Phenylalanine Ammonia-Lyase Gene (SsPAL1) from Coleus (Solenostemon scutellarioides (L.) Codd)
Molecules 2015, 20(9), 16833-16851; doi:10.3390/molecules200916833
Received: 9 June 2015 / Revised: 20 August 2015 / Accepted: 31 August 2015 / Published: 16 September 2015
Cited by 3 | PDF Full-text (3779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phenylalanine ammonia-lyase (PAL) is the first enzyme involved in the phenylpropanoid pathway and plays important roles in the secondary metabolisms, development and defense of plants. To study the molecular function of PAL in anthocyanin synthesis of Coleus (Solenostemon scutellarioides (L.) Codd),
[...] Read more.
Phenylalanine ammonia-lyase (PAL) is the first enzyme involved in the phenylpropanoid pathway and plays important roles in the secondary metabolisms, development and defense of plants. To study the molecular function of PAL in anthocyanin synthesis of Coleus (Solenostemon scutellarioides (L.) Codd), a Coleus PAL gene designated as SsPAL1 was cloned and characterized using a degenerate oligonucleotide primer PCR and RACE method. The full-length SsPAL1 was 2450 bp in size and consisted of one intron and two exons encoding a polypeptide of 711 amino acids. The deduced SsPAL1 protein showed high identities and structural similarities with other functional plant PAL proteins. A series of putative cis-acting elements involved in transcriptional regulation, light and stress responsiveness were found in the upstream regulatory sequence of SsPAL1. Transcription pattern analysis indicated that SsPAL1 was constitutively expressed in all tissues examined and was enhanced by light and different abiotic factors. The recombinant SsPAL1 protein exhibited high PAL activity, at optimal conditions of 60 °C and pH 8.2. Although the levels of total PAL activity and total anthocyanin concentration have a similar variation trend in different Coleus cultivars, there was no significant correlation between them (r = 0.7529, p > 0.1), suggesting that PAL was not the rate-limiting enzyme for the downstream anthocyanin biosynthetic branch in Coleus. This study enables us to further understand the role of SsPAL1 in the phenylpropanoid (flavonoids, anthocyanins) biosynthesis in Coleus at the molecular level. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Preparation and Reaction Chemistry of Novel Silicon-Substituted 1,3-Dienes
Molecules 2015, 20(9), 16892-16907; doi:10.3390/molecules200916892
Received: 17 August 2015 / Revised: 7 September 2015 / Accepted: 8 September 2015 / Published: 16 September 2015
Cited by 2 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
2-Silicon-substituted 1,3-dienes containing non transferrable groups known to promote transmetallation were prepared by Grignard chemistry and enyne metathesis. These dienes participated in one pot metathesis/Diels-Alder reactions in regio- and diastereoselective fashions. Electron-rich alkenes showed the fastest rates in metathesis reactions, and ethylene, a
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2-Silicon-substituted 1,3-dienes containing non transferrable groups known to promote transmetallation were prepared by Grignard chemistry and enyne metathesis. These dienes participated in one pot metathesis/Diels-Alder reactions in regio- and diastereoselective fashions. Electron-rich alkenes showed the fastest rates in metathesis reactions, and ethylene, a commonly used metathesis promoter slowed enyne metathesis. 2-Pyridyldimethylsilyl and 2-thienyldimethylsilyl substituted Diels-Alder cycloadducts participated in cross-coupling chemistry and the 2-thienyldimethylsilyl substituted cycloadducts underwent cross-coupling under very mild reaction conditions. Full article
(This article belongs to the Special Issue Olefin Metathesis)
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Open AccessArticle Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway
Molecules 2015, 20(9), 16908-16923; doi:10.3390/molecules200916908
Received: 4 July 2015 / Revised: 3 September 2015 / Accepted: 10 September 2015 / Published: 17 September 2015
Cited by 2 | PDF Full-text (2819 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent
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Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Diterpenoids from the Endophytic Fungus Botryosphaeria sp. P483 of the Chinese Herbal Medicine Huperzia serrata
Molecules 2015, 20(9), 16924-16932; doi:10.3390/molecules200916924
Received: 16 July 2015 / Revised: 7 September 2015 / Accepted: 9 September 2015 / Published: 17 September 2015
Cited by 3 | PDF Full-text (736 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new tetranorlabdane diterpenoids, named botryosphaerins G (1) and H (2), were isolated from the solid fermentation products of Botryosphaeria sp. P483 along with seven known tetranorlabdane diterpenes (39). Their structures were elucidated by extensive
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Two new tetranorlabdane diterpenoids, named botryosphaerins G (1) and H (2), were isolated from the solid fermentation products of Botryosphaeria sp. P483 along with seven known tetranorlabdane diterpenes (39). Their structures were elucidated by extensive analysis, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). Their absolute configuration was confirmed by single-crystal X-ray diffraction analyses using the anomalous scattering of Cu Kα radiation. All of the isolated compounds were tested for activity against phytopathogenic fungi and nematodes. Compounds 2 and 3 showed antifungal activity and compound 2 showed weak nematicidal activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors
Molecules 2015, 20(9), 16933-16945; doi:10.3390/molecules200916933
Received: 15 June 2015 / Revised: 2 September 2015 / Accepted: 10 September 2015 / Published: 17 September 2015
Cited by 9 | PDF Full-text (907 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (1), a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore,
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Resveratrol (1), a naturally occurring stilbene compound, has been suggested as a potential whitening agent with strong inhibitory activity on melanin synthesis. However, the use of resveratrol in cosmetics has been limited due to its chemical instability and poor bioavailability. Therefore, resveratrol derivatives were prepared to improve bioavailability and anti-melanogenesis activity. Nine resveratrol derivatives including five alkyl ether derivatives with C2H5, C4H9, C5H11, C6H13, and C8H17 (2a2e) and four ester derivatives with CH3, CH=C(CH3)2, CH(C2H5)C4H9, C7H15 (3a3d) were newly synthesized and their effect on melanin synthesis were assessed. All the synthetic derivatives efficiently reduced the melanin content in α-MSH stimulated B16F10 melanoma cells. Further investigation showed that the inhibitory effect of 2a on melanin synthesis was achieved not by the inhibition of tyrosinase activity but by the inhibition of melanogenic enzyme expressions such as tyrosinase and tyrosinase-related protein (TRP)-1. Our synthetic resveratrol derivatives have more lipophilic properties than resveratrol by the addition of alkyl or acyl chains to free hydroxyl moiety of resveratrol; thus, they are expected to show better bioavailability in skin application. Therefore, we suggest that our synthetic resveratrol derivatives might be promising candidates for better practical application to skin-whitening cosmetics. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions
Molecules 2015, 20(9), 16946-16969; doi:10.3390/molecules200916946
Received: 30 July 2015 / Revised: 24 August 2015 / Accepted: 9 September 2015 / Published: 17 September 2015
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Abstract
This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv.) under field conditions. Grape bunches were wrapped with two types of polyester films that cut off
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This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv.) under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A) and 99% (film B) invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA) revealed that (E)-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E)-2-heptenal, styrene, α-phenylethanol, and (Z)-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation. Full article
(This article belongs to the collection Wine Chemistry)
Open AccessArticle A Novel Reduplicate Strategy for Tracing Hemostatic Compounds from Heating Products of the Flavonoid Extract in Platycladi cacumen by Spectrum-Effect Relationships and Column Chromatography
Molecules 2015, 20(9), 16970-16986; doi:10.3390/molecules200916970
Received: 1 August 2015 / Revised: 8 September 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
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Abstract
Platycladi cacumen and its processed product have been utilized as a Chinese medicine to treat hemorrhages. In this study, the base peak chromatogram fingerprints of heating products of total flavonoids in Platycladi cacumen were established by high performance liquid chromatography coupled with mass
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Platycladi cacumen and its processed product have been utilized as a Chinese medicine to treat hemorrhages. In this study, the base peak chromatogram fingerprints of heating products of total flavonoids in Platycladi cacumen were established by high performance liquid chromatography coupled with mass spectroscopy/mass spectroscopy (HPLC-MS/MS), and the hemostatic activities were studied by hemostatic screening tests in vivo. The spectrum-effect relationships between fingerprints and hemostatic activities were analyzed by using canonical correlation analysis to trace the peaks responsible for the significant hemostatic effects. Peak 10 and peak 12 were correlated most closely, thus probably being the main hemostatic compounds. To confirm the reliability of this strategy, the targeted unknown peak was obtained by bioactivity-guided isolation, characterized by MS, 1H-NMR, 13C-NMR, and 2D-NMR spectroscopies, and referred to as cecarbon as a new compound. In addition, the isolated compound exhibited hemostatic effect in a dose-dependent manner with different potencies in vitro and existed in Platycladi cacumen Carbonisatus. A novel dereplication strategy was employed to trace and identify the active compounds of other herbs that have bioactivity enhancement after processing using spectrum–effect relationships and column chromatography. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis and Biological Activity of Isoflavone Derivatives from Chickpea as Potent Anti-Diabetic Agents
Molecules 2015, 20(9), 17016-17040; doi:10.3390/molecules200917016
Received: 20 July 2015 / Revised: 30 August 2015 / Accepted: 3 September 2015 / Published: 17 September 2015
Cited by 1 | PDF Full-text (9651 KB) | HTML Full-text | XML Full-text
Abstract
A set of novel isoflavone derivatives from chickpea were synthesized. The structures of derivatives were identified by proton nuclear magnetic resonance (1H-NMR), carbon-13 (13C)-NMR and mass spectrometry (MS) spectral analyses. Their anti-diabetic activities were evaluated using an insulin-resistant (IR)
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A set of novel isoflavone derivatives from chickpea were synthesized. The structures of derivatives were identified by proton nuclear magnetic resonance (1H-NMR), carbon-13 (13C)-NMR and mass spectrometry (MS) spectral analyses. Their anti-diabetic activities were evaluated using an insulin-resistant (IR) HepG2 cell model. Additionally, the structure-activity relationships of these derivatives were briefly discussed. Compounds 1c, 2h, 3b, and 5 and genistein exhibited significant glucose consumption-enhancing effects in IR-HepG2 cells. In addition, the combinations of genistein, 2h, and 3b (combination 6) and of 3b, genistein, and 1c (combination 10) exhibited better anti-diabetic activity than the individual compounds. At the same dosage, there was no difference in effect between the combination 10 and the positive control (p > 0.05). Aditionally, we found the differences between the combination 10 and combination 6 for the protective effect of HUVEC (human umbilical vein endothelial cells) under high glucose concentration. The protective effects of combination 10 was stronger than combination 6, which suggested that combination 10 may have a better hypoglycemic activity in future studies. This study provides useful clues for the further design and discovery of anti-diabetic agents. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Stereoselective Formation of Substituted 1,3-Dioxolanes through a Three-Component Assembly during the Oxidation of Alkenes with Hypervalent Iodine(III)
Molecules 2015, 20(9), 17041-17057; doi:10.3390/molecules200917041
Received: 14 August 2015 / Revised: 9 September 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
Cited by 3 | PDF Full-text (790 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Stereoselective formation of substituted 1,3-dioxolanes was achieved through an assembly of three components: alkene, carboxylic acid and silyl enol ether. The reaction proceeded via stereospecific generation of a 1,3-dioxolan-2-yl cation intermediate during oxidation of alkene substrates with hypervalent iodine. The stereoselective trapping of
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Stereoselective formation of substituted 1,3-dioxolanes was achieved through an assembly of three components: alkene, carboxylic acid and silyl enol ether. The reaction proceeded via stereospecific generation of a 1,3-dioxolan-2-yl cation intermediate during oxidation of alkene substrates with hypervalent iodine. The stereoselective trapping of the cation intermediate with silyl enol ether completed the formation of the dioxolane product. Full article
(This article belongs to the Special Issue Hypervalent Iodine Chemistry)
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Open AccessCommunication Transfer Hydrogenation Employing Ethylene Diamine Bisborane in Water and Pd- and Ru-Nanoparticles in Ionic Liquids
Molecules 2015, 20(9), 17058-17069; doi:10.3390/molecules200917058
Received: 2 April 2015 / Revised: 31 August 2015 / Accepted: 8 September 2015 / Published: 17 September 2015
Cited by 2 | PDF Full-text (729 KB) | HTML Full-text | XML Full-text
Abstract
Herein we demonstrate the use of ethylenediamine bisborane (EDAB) as a suitable hydrogen source for transfer hydrogenation reactions on C-C double bonds mediated by metal nanoparticles. Moreover, EDAB also acts as a reducing agent for carbonyl functionalities in water under metal-free conditions. Full article
(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)
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Open AccessArticle Antibacterial and Anti-Quorum Sensing Molecular Composition Derived from Quercus cortex (Oak bark) Extract
Molecules 2015, 20(9), 17093-17108; doi:10.3390/molecules200917093
Received: 16 June 2015 / Revised: 26 August 2015 / Accepted: 7 September 2015 / Published: 17 September 2015
Cited by 4 | PDF Full-text (1491 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quercus cortex (Oak bark) has been used in European folk medicine since medieval times for treatment of diarrhea, stomatitis, pharyngitis and skin inflammations. Its antimicrobial activity is a well-known therapeutic property of oak bark, and its novel anti-quorum sensing (QS) ability has also
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Quercus cortex (Oak bark) has been used in European folk medicine since medieval times for treatment of diarrhea, stomatitis, pharyngitis and skin inflammations. Its antimicrobial activity is a well-known therapeutic property of oak bark, and its novel anti-quorum sensing (QS) ability has also been described recently. In this study, we examined the bioactive compounds of Quercus cortex extract and compared their direct antibacterial and regulatory anti-QS effects against Chromobacterium violaceum CV026 in a biotest. Evaluation of the original Quercus cortex extract showed weak antibacterial and prominent anti-QS activities that were retained and completely restored when the samples were dried and re-hydrated. The one-step liquid chromatography result indicated that the anti-QS activity might be determined by hydrophobic compounds; however, the subsequent reverse phase high performance liquid chromatography led to dissipation and loss of the activity. The gas chromatography–mass spectrometry gave excellent resolution between a majority of the compounds. Based on this result, 10 of the 35 identified small molecules were selected for further screening. The subsequent investigation indicated several compounds determined both the antibacterial and anti-QS activities of the Quercus cortex extract. Direct antibacterial activity was shown for 1,2,3-benzenetriol and 4-propyl-1,3-benzenediol, while sub-inhibitory concentrations of these compounds led to anti-QS effects. Five compounds: 4-(3-hydroxy-1-propenyl)-2-methoxy-phenol; 3,4,5-trimethoxyphenol; 4-hydroxy-3-methoxybenzaldehyde; 7-hydroxy-6-methoxy-2H-1-benzopyran-2-one and 2H-1-benzopyran-2-one were characterized as QS inhibitors independent of any effect on bacterial growth. Biologically relevant concentrations of each single component showed weak activity only while reconstruction of the small molecule composition derived from the Quercus cortex extract provided comparable complementary activity against C. violaceum CV026 in the biotest as the crude extract. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Study on the Condensation Reaction of 4-Amino-3,5-dimethyl-1,2,4-triazole with Benzaldehydes: Structure and Spectroscopic Properties of Some New Stable Hemiaminals
Molecules 2015, 20(9), 17109-17131; doi:10.3390/molecules200917109
Received: 15 July 2015 / Revised: 7 September 2015 / Accepted: 9 September 2015 / Published: 17 September 2015
Cited by 3 | PDF Full-text (1716 KB) | HTML Full-text | XML Full-text
Abstract
Studies on the stable hemiaminals and Schiff bases formation in the reaction of substituted benzaldehydes with primary 3,5-dimethyl-1,2,4-triazole 4-amine were carried out under neutral conditions. These products were investigated by IR, Raman, MS, 1H- and 13C-NMR spectra as well as by
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Studies on the stable hemiaminals and Schiff bases formation in the reaction of substituted benzaldehydes with primary 3,5-dimethyl-1,2,4-triazole 4-amine were carried out under neutral conditions. These products were investigated by IR, Raman, MS, 1H- and 13C-NMR spectra as well as by X-ray crystallography. The effect of reaction conditions: temperature, polarity of the solvents utilized, substrate concentration and the ortho and para benzaldehyde substituents on the yield of products was also examined. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Comparative Analysis of Virtual Screening Approaches in the Search for Novel EphA2 Receptor Antagonists
Molecules 2015, 20(9), 17132-17151; doi:10.3390/molecules200917132
Received: 3 August 2015 / Revised: 8 September 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
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Abstract
The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2
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The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2 receptor. However, these compounds suffer from poor physicochemical properties, hampering their use in vivo. The identification of compounds able to disrupt the EphA2-ephrin-A1 complex lacking the bile acid scaffold may lead to new pharmacological tools suitable for in vivo studies. To identify the most promising virtual screening (VS) protocol aimed at finding novel EphA2 antagonists, we investigated the ability of both ligand-based and structure-based approaches to retrieve known EphA2 antagonists from libraries of decoys with similar molecular properties. While ligand-based VSs were conducted using UniPR129 and ephrin-A1 ligand as reference structures, structure-based VSs were performed with Glide, using the X-ray structure of the EphA2 receptor/ephrin-A1 complex. A comparison of enrichment factors showed that ligand-based approaches outperformed the structure-based ones, suggesting ligand-based methods using the G-H loop of ephrin-A1 ligand as template as the most promising protocols to search for novel EphA2 antagonists. Full article
(This article belongs to the Special Issue Small Molecules Modulation in Protein-Protein Interactions)
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Open AccessArticle Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents
Molecules 2015, 20(9), 17152-17165; doi:10.3390/molecules200917152
Received: 20 July 2015 / Revised: 10 September 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
Cited by 6 | PDF Full-text (889 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of 5H-chromenopyridines was identified as anticancer agents in our continuing effort to discover and develop new small molecule anti-proliferative agents. Based on our initial lead SP-6-27 compound, we designed and synthesized novel tricyclic 5H-thiochromenopyridine and 5
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A novel series of 5H-chromenopyridines was identified as anticancer agents in our continuing effort to discover and develop new small molecule anti-proliferative agents. Based on our initial lead SP-6-27 compound, we designed and synthesized novel tricyclic 5H-thiochromenopyridine and 5H-chromenopyridine analogs to evaluate the impact of an additional ring, as well as conformational flexibility on cytotoxic activity against human melanoma and glioma cell lines. All of the 5H-thiochromenopyridines have been achieved in good yields (89%–93%) using a single-step, three-component cyclization without the need for purification. The 5H-chromenopyridine analog of the potent 5H-thiochromenopyride was obtained in a good yield upon purification. All newly-prepared 5H-thiochromenopyridines showed good to moderate cytotoxicity against three melanoma and two glioma cell lines (3–15 μM). However, the 5H-chromenopyridine analogue that we prepared in our laboratory lost cytotoxic activity. The moderate cytotoxic activity of 5H-thiochromenopyridines shows the promise of developing chromenopyridines as potential anticancer agents. Full article
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Open AccessArticle Blumea balsamifera Oil for the Acceleration of Healing of Burn Injuries
Molecules 2015, 20(9), 17166-17179; doi:10.3390/molecules200917166
Received: 12 June 2015 / Revised: 2 September 2015 / Accepted: 14 September 2015 / Published: 17 September 2015
Cited by 3 | PDF Full-text (5307 KB) | HTML Full-text | XML Full-text
Abstract
Blumea balsamifera oil (BBO) is a main extract obtained from Blumea balsamifera (L.) DC (Ainaxiang) leaves, which are widely used as a traditional medicine by the Miao and Li Nations to promote skin trauma or burn injury healing. This study was initiated to
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Blumea balsamifera oil (BBO) is a main extract obtained from Blumea balsamifera (L.) DC (Ainaxiang) leaves, which are widely used as a traditional medicine by the Miao and Li Nations to promote skin trauma or burn injury healing. This study was initiated to investigate the healing efficacy in deep second-degree burn model in rats. The rats were treated by BBO for 21 consecutive days. The rate of healing, scabs dropped time and re-epithelialization time were observed every three days for 21 days after burn injury. The samples were collected from different treated rats by sacrificing the animals on the 1st, 2nd, 5th, 9th, 14th, and 21st day post-burn creation. Then, the water content of burn tissue was measured. Plasma interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) levels were evaluated, and the tissue expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) were determined along with skin histopathology. The results showed that the water content of tissue was significantly reduced, the scabs dropped time shortened, and healing accelerated after treatment with BBO in the burn injury rats. Furthermore, the expressions of growth factors were significantly increased in the tissue; however, the levels of inflammatory factors on plasma decreased. This study confirms the efficacy of BBO consumption on burn injuries. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Investigation of Film with β-Galactosidase Designed for Stabilization and Handling in Dry Configuration
Molecules 2015, 20(9), 17180-17193; doi:10.3390/molecules200917180
Received: 25 March 2015 / Revised: 28 August 2015 / Accepted: 31 August 2015 / Published: 18 September 2015
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Abstract
Gelatin-based films with an immobilized enzyme designed for extending the stability of the protein in dry, non-powder configuration with precise dosing attributes were subjected to stress conditions of temperature and relative humidity. β-galactosidase was used as model functional protein. The film configuration preserved
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Gelatin-based films with an immobilized enzyme designed for extending the stability of the protein in dry, non-powder configuration with precise dosing attributes were subjected to stress conditions of temperature and relative humidity. β-galactosidase was used as model functional protein. The film configuration preserved the activity of the enzyme under the different storage conditions investigated, which include room temperature under low (ambient) and high (75%) relative humidity, and 36 °C under low (oven) and high relative humidity conditions for a period of 46 days. The influence of the enzyme and plasticizer (glycerol) on the physical and mechanical properties of the films was investigated using DMA (dynamic mechanical analysis). Films containing 5% β-galactosisdase and glycerol concentrations of 14% or greater exhibited greater tensile strength, Young’s modulus, and elongation at break than films with equal concentrations of plasticizer but devoid of any enzyme. The surface texture of the films was analyzed using scanning electron microscopy (SEM). β-galactosidase and glycerol have opposite effects on the surface morphology of the films. Increasing concentrations of the enzyme result in rougher film surface, whereas increasing the concentration of glycerol leads to films with denser and smoother surface. The results obtained suggest that the dry film configuration approach can help in facilitating the stabilization, handling, storage, and transportation of functional proteins in a cost effective manner. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Influence of Laccase and Tyrosinase on the Antioxidant Capacity of Selected Phenolic Compounds on Human Cell Lines
Molecules 2015, 20(9), 17194-17207; doi:10.3390/molecules200917194
Received: 30 June 2015 / Revised: 25 August 2015 / Accepted: 11 September 2015 / Published: 18 September 2015
Cited by 3 | PDF Full-text (918 KB) | HTML Full-text | XML Full-text
Abstract
Polyphenolic compounds affect the color, odor and taste of numerous food products of plant origin. In addition to the visual and gustatory properties, they serve as radical scavengers and have antioxidant effects. Polyphenols, especially resveratrol in red wine, have gained increasing scientific and
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Polyphenolic compounds affect the color, odor and taste of numerous food products of plant origin. In addition to the visual and gustatory properties, they serve as radical scavengers and have antioxidant effects. Polyphenols, especially resveratrol in red wine, have gained increasing scientific and public interest due to their presumptive beneficial impact on human health. Enzymatic oxidation of phenolic compounds takes place under the influence of polyphenol oxidases (PPO), including tyrosinase and laccase. Several studies have demonstrated the radical scavenger effect of plants, food products and individual polyphenols in vitro, but, apart from resveratrol, such impact has not been proved in physiological test systems. Furthermore, only a few data exist on the antioxidant capacities of the enzymatic oxidation products of phenolic compounds generated by PPO. We report here first results about the antioxidant effects of phenolic substances, before and after oxidation by fungal model tyrosinase and laccase. In general, the common chemical 2,2-diphenyl-1-picrylhydrazyl assay and the biological tests using two different types of cell cultures (monocytes and endothelial cells) delivered similar results. The phenols tested showed significant differences with respect to their antioxidant activity in all test systems. Their antioxidant capacities after enzymatic conversion decreased or increased depending on the individual PPO used. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Asymmetric Synthesis of 1,3-Oxazolidine Derivatives with Multi-Component Reaction and Research of Kinetic Resolution
Molecules 2015, 20(9), 17208-17220; doi:10.3390/molecules200917208
Received: 26 May 2015 / Revised: 31 August 2015 / Accepted: 1 September 2015 / Published: 18 September 2015
Cited by 2 | PDF Full-text (800 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The plausible mechanism was proposed and a kinetic resolution of epoxides process was
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An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The plausible mechanism was proposed and a kinetic resolution of epoxides process was confirmed. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Chemical Composition Analysis, Antimicrobial Activity and Cytotoxicity Screening of Moss Extracts (Moss Phytochemistry)
Molecules 2015, 20(9), 17221-17243; doi:10.3390/molecules200917221
Received: 29 July 2015 / Revised: 6 September 2015 / Accepted: 10 September 2015 / Published: 18 September 2015
Cited by 5 | PDF Full-text (1122 KB) | HTML Full-text | XML Full-text
Abstract
Mosses have been neglected as a study subject for a long time. Recent research shows that mosses contain remarkable and unique substances with high biological activity. The aim of this study, accordingly, was to analyze the composition of mosses and to screen their
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Mosses have been neglected as a study subject for a long time. Recent research shows that mosses contain remarkable and unique substances with high biological activity. The aim of this study, accordingly, was to analyze the composition of mosses and to screen their antimicrobial and anticancer activity. The total concentration of polyphenols and carbohydrates, the amount of dry residue and the radical scavenging activity were determined for a preliminary evaluation of the chemical composition of moss extracts. In order to analyze and identify the substances present in mosses, two types of extrahents (chloroform, ethanol) and the GC/MS and LC-TOF-MS methods were used. The antimicrobial activity was tested on four bacteria strains, and the anticancer activity on six cancer cell lines. The obtained results show the presence of a high number of primary (fatty acids and amino acids), but mainly secondary metabolites in moss extracts—including, sterols, terpenoids, polyphenols and others—and a high activity with respect to the studied test organisms. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
Molecules 2015, 20(9), 17275-17287; doi:10.3390/molecules200917275
Received: 13 July 2015 / Revised: 9 September 2015 / Accepted: 14 September 2015 / Published: 18 September 2015
PDF Full-text (1414 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl-3-cyano-2,6-dihydroxypyridine intermediate. A different selectivity according to the nature of the aryl group has been observed. Compound
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A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl-3-cyano-2,6-dihydroxypyridine intermediate. A different selectivity according to the nature of the aryl group has been observed. Compound 9b is a selective inhibitor against the PI3Kα isoform, maintaining a good inhibitory activity. Docking studies were also performed in order to rationalize its profile of selectivity. Full article
(This article belongs to the Special Issue Kinase Inhibitor Chemistry)
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Open AccessArticle Effect of Amaranthus on Advanced Glycation End-Products Induced Cytotoxicity and Proinflammatory Cytokine Gene Expression in SH-SY5Y Cells
Molecules 2015, 20(9), 17288-17308; doi:10.3390/molecules200917288
Received: 30 July 2015 / Revised: 11 September 2015 / Accepted: 11 September 2015 / Published: 18 September 2015
Cited by 2 | PDF Full-text (1212 KB) | HTML Full-text | XML Full-text
Abstract
Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Advanced glycation end-products (AGEs)
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Amaranthus plants, or spinach, are used extensively as a vegetable and are known to possess medicinal properties. Neuroinflammation and oxidative stress play a major role in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Advanced glycation end-products (AGEs) cause cell toxicity in the human neuronal cell line, SH-SY5Y, through an increase in oxidative stress, as shown by reducing cell viability and increasing cell toxicity in a dose-dependent manner. We found that preincubation of SH-SY5Y cells with either petroleum ether, dichloromethane or methanol extracts of A. lividus and A. tricolor dose-dependently attenuated the neuron toxicity caused by AGEs treatment. Moreover, the results showed that A. lividus and A. tricolor extracts significantly downregulated the gene expression of the pro-inflammatory cytokines, TNF-α, IL-1 and IL-6 genes in AGEs-induced cells. We concluded that A. lividus and A. tricolor extracts not only have a neuroprotective effect against AGEs toxicity, but also have anti-inflammatory activity by reducing pro-inflammatory cytokine gene expression. This suggests that Amaranthus may be useful for treating chronic inflammation associated with neurodegenerative disorders. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Acylphloroglucinol Derivatives from the South African Helichrysum niveum and Their Biological Activities
Molecules 2015, 20(9), 17309-17324; doi:10.3390/molecules200917309
Received: 23 July 2015 / Revised: 8 September 2015 / Accepted: 10 September 2015 / Published: 18 September 2015
Cited by 1 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of aerial parts of Helichrysum niveum (H. niveum) using different chromatographic methods including semi-preparative HPLC afforded three new (13) and six known (410) acylphloroglucinols alongside a known dialcohol triterpene (11
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Phytochemical investigation of aerial parts of Helichrysum niveum (H. niveum) using different chromatographic methods including semi-preparative HPLC afforded three new (13) and six known (410) acylphloroglucinols alongside a known dialcohol triterpene (11). The structures of the isolated compounds were characterized accordingly as 1-benzoyl-3 (3-methylbut-2-enylacetate)-phloroglucinol (helinivene A, 1), 1-benzoyl-3 (2S-hydroxyl-3-methylbut-3-enyl)-phloroglucinol (helinivene B, 2), 8-(2-methylpropanone)-3S,5,7-trihydroxyl-2,2-dimethoxychromane (helinivene C, 3), 1-(2-methylbutanone)-4-O-prenyl-phloroglucinol (4), 1-(2-methylpropanone)-4-O-prennyl-phloroglucinol (5), 1-(butanone)-3-prenyl-phloroglucinol (6), 1-(2-methylbutanone)-3-prenyl-phloroglucinol (7), 1-butanone-3-(3-methylbut-2-enylacetate)-phloroglucinol (8), 1-(2-methylpropanone)-3-prenylphloroglucinol (9), caespitate (10), and 3β-24-dihydroxyterexer-14-ene (11). Excellent total antioxidant capacities were demonstrated by helinivenes A and B (1 and 2) when measured as oxygen radicals absorbance capacity (ORAC), ferric-ion reducing antioxidant power (FRAP), trolox equivalent absorbance capacity (TEAC) and including the inhibition of Fe2+-induced lipid peroxidation (IC50 = 5.12 ± 0.90; 3.55 ± 1.92) µg/mL, while anti-tyrosinase activity at IC50 = 35.63 ± 4.67 and 26.72 ± 5.05 µg/mL were also observed for 1 and 2, respectively. This is the first chemical and in vitro biological study on H. niveum. These findings underpin new perspectives for the exploitation of these natural phenolic compounds in applications such as in the natural cosmeceutical and pharmaceutical sectors. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle New Hydrazones Bearing Thiazole Scaffold: Synthesis, Characterization, Antimicrobial, and Antioxidant Investigation
Molecules 2015, 20(9), 17325-17338; doi:10.3390/molecules200917325
Received: 26 July 2015 / Revised: 3 September 2015 / Accepted: 9 September 2015 / Published: 18 September 2015
Cited by 4 | PDF Full-text (836 KB) | HTML Full-text | XML Full-text
Abstract
New series of hydrazones 5–18 were synthesized, in good yields, by reacting 4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole-5-carbohydrazide with differently substituted benzaldehyde. The resulting compounds were characterized via elemental analysis, physico-chemical and spectral data. An antimicrobial screening was done, using Gram (+), Gram (−) bacteria and one fungal
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New series of hydrazones 5–18 were synthesized, in good yields, by reacting 4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole-5-carbohydrazide with differently substituted benzaldehyde. The resulting compounds were characterized via elemental analysis, physico-chemical and spectral data. An antimicrobial screening was done, using Gram (+), Gram (−) bacteria and one fungal strain. Tested molecules displayed moderate-to-good growth inhibition activity. 2,2-Diphenyl-1-picrylhydrazide assay was used to test the antioxidant properties of the compounds. Monohydroxy (14–16), para-fluorine (13) and 2,4-dichlorine (17) derivatives exhibited better free-radical scavenging ability than the other investigated molecules. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Isoindigo-Based Small Molecules with Varied Donor Components for Solution-Processable Organic Field Effect Transistor Devices
Molecules 2015, 20(9), 17362-17377; doi:10.3390/molecules200917362
Received: 3 August 2015 / Revised: 15 September 2015 / Accepted: 15 September 2015 / Published: 18 September 2015
Cited by 2 | PDF Full-text (7400 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two solution-processable small organic molecules, (E)-6,6′-bis(4-(diphenylamino)phenyl)-1,1′-bis(2-ethylhexyl)-(3,3′-biindolinylidene)-2,2′-dione (coded as S10) and (E)-6,6′-di(9H-carbazol-9-yl)-1,1′-bis(2-ethylhexyl)-(3,3′-biindolinylidene)-2,2′-dione (coded as S11) were successfully designed, synthesized and fully characterized. S10 and S11 are based on a donor-acceptor-donor structural motif and contain a common
[...] Read more.
Two solution-processable small organic molecules, (E)-6,6′-bis(4-(diphenylamino)phenyl)-1,1′-bis(2-ethylhexyl)-(3,3′-biindolinylidene)-2,2′-dione (coded as S10) and (E)-6,6′-di(9H-carbazol-9-yl)-1,1′-bis(2-ethylhexyl)-(3,3′-biindolinylidene)-2,2′-dione (coded as S11) were successfully designed, synthesized and fully characterized. S10 and S11 are based on a donor-acceptor-donor structural motif and contain a common electron accepting moiety, isoindigo, along with different electron donating functionalities, triphenylamine and carbazole, respectively. Ultraviolet-visible absorption spectra revealed that the use of triphenylamine donor functionality resulted in an enhanced intramolecular charge transfer transition and reduction of optical band gap, when compared with its carbazole analogue. Both of these materials were designed to be donor semiconducting components, exerted excellent solubility in common organic solvents, showed excellent thermal stability, and their promising optoelectronic properties encouraged us to scrutinize charge-carrier mobilities using solution-processable organic field effect transistors. Hole mobilities of the order of 2.2 × 10−4 cm2/Vs and 7.8 × 10−3 cm2/Vs were measured using S10 and S11 as active materials, respectively. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Preparation of Thermo-Responsive Poly(ionic liquid)s-Based Nanogels via One-Step Cross-Linking Copolymerization
Molecules 2015, 20(9), 17378-17392; doi:10.3390/molecules200917378
Received: 11 August 2015 / Revised: 11 September 2015 / Accepted: 14 September 2015 / Published: 18 September 2015
Cited by 5 | PDF Full-text (1745 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, thermo-responsive polymeric nanogels were facilely prepared via one-step cross-linking copolymerization of ethylene glycol dimethacrylate/divinylbenzene and ionic liquid (IL)-based monomers, 1,n-dialkyl-3,3′-bis-1-vinyl imidazolium bromides ([CnVIm]Br; n = 6, 8, 12) in selective solvents. The results revealed that stable and blue
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In this study, thermo-responsive polymeric nanogels were facilely prepared via one-step cross-linking copolymerization of ethylene glycol dimethacrylate/divinylbenzene and ionic liquid (IL)-based monomers, 1,n-dialkyl-3,3′-bis-1-vinyl imidazolium bromides ([CnVIm]Br; n = 6, 8, 12) in selective solvents. The results revealed that stable and blue opalescent biimidazolium (BIm)-based nanogel solutions could be obtained without any precipitation when the copolymerizations were conducted in methanol. Most importantly, these novel nanogels were thermo-response, and could reversibly transform to precipitation in methanol with temperature changes. Turbidity analysis and dynamic light scatting (DLS) measurement illustrated that PIL-based nanogel solutions presented the phase transform with upper critical solution temperature (UCST) in the range of 5–25 °C. The nanogels were characterized using Fourier transform infrared (FTIR), thermogravimetric analyses (TGA), and scanning electron microscopy (SEM). In addition, BIm-based nanogels could also be used as highly active catalysts in the cycloaddition reaction of CO2 and epoxides. As a result, our attributes build a robust platform suitable for the preparation of polymeric nanomaterials, as well as CO2 conversion. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Open AccessArticle Selected Phytochemicals and Culinary Plant Extracts Inhibit Fructose Uptake in Caco-2 Cells
Molecules 2015, 20(9), 17393-17404; doi:10.3390/molecules200917393
Received: 31 July 2015 / Revised: 1 September 2015 / Accepted: 15 September 2015 / Published: 18 September 2015
Cited by 4 | PDF Full-text (2433 KB) | HTML Full-text | XML Full-text
Abstract
This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid
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This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid chromatography with mass spectrometry. Inhibition of [14C]-fructose uptake was tested by using human intestinal Caco-2 cells. Then, the relative contribution of the two apical-facing intestinal fructose transporters, GLUT2 and GLUT5, and the signature components for fructose uptake inhibition was confirmed in naive, phloretin-treated and forskolin-treated Caco-2 cells. HPLC/MS analysis of the chemical signature revealed that guava leaf contained quercetin and catechin, and turmeric contained curcumin, bisdemethoxycurcumin and dimethoxycurcumin. Similar inhibition of fructose uptake (by ~50%) was observed with guava leaf and turmeric in Caco-2 cells, but with a higher contribution of GLUT2 for turmeric and that of GLUT5 for guava leaf. The data suggested that, in turmeric, demethoxycurcumin specifically contributed to GLUT2-mediated fructose uptake inhibition, and curcumin did the same to GLUT5-mediated fructose uptake inhibition, but GLUT2 inhibition was more potent. By contrast, in guava leaf, catechin specifically contributed to GLUT5-mediated fructose uptake inhibition, and quercetin affected both GLUT5- and GLUT2-mediated fructose uptake inhibition, resulting in the higher contribution of GLUT5. These results suggest that demethoxycurcumin is an important contributor to GLUT2-mediated fructose uptake inhibition for turmeric extract, and catechin is the same to GLUT5-mediated fructose uptake inhibition for guava leaf extract. Quercetin, curcumin and bisdemethoxycurcumin contributed to both GLUT5- and GLUT2-mediated fructose uptake inhibition, but the contribution to GLUT5 inhibition was higher than the contribution to GLUT2 inhibition. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Clinacanthus nutans (Burm. f.) Lindau Ethanol Extract Inhibits Hepatoma in Mice through Upregulation of the Immune Response
Molecules 2015, 20(9), 17405-17428; doi:10.3390/molecules200917405
Received: 19 April 2015 / Revised: 1 September 2015 / Accepted: 9 September 2015 / Published: 18 September 2015
Cited by 8 | PDF Full-text (16381 KB) | HTML Full-text | XML Full-text
Abstract
Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor
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Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ+ T cells and decreased the number of IL-4+ T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Biscoumarin and Dihydropyran Derivatives and Evaluation of Their Antibacterial Activity
Molecules 2015, 20(9), 17469-17482; doi:10.3390/molecules200917469
Received: 27 April 2015 / Revised: 25 June 2015 / Accepted: 22 July 2015 / Published: 18 September 2015
Cited by 12 | PDF Full-text (1723 KB) | HTML Full-text | XML Full-text
Abstract
In an attempt to find a new class antibacterial agents, a series of biscoumarins (14) and dihydropyrans (513) were successfully prepared. The molecular structures of four representative compounds, that is, 4, 5, 8
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In an attempt to find a new class antibacterial agents, a series of biscoumarins (14) and dihydropyrans (513) were successfully prepared. The molecular structures of four representative compounds, that is, 4, 5, 8 and 12 were confirmed by single crystal X-ray diffraction study. These synthesized compounds were screened for their antibacterial activity in vitro against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), USA 300 (Los Angeles County clone, LAC), Staphylococcus epidermidis (S. epidermidis ATCC 14990), methicillin-resistant S. epidermidis (MRSE XJ 75284) and Escherichia coli (E. coli ATCC 25922). Additionally, there are two classical intramolecular O–H···O hydrogen bonds (HBs) in biscoumarins 14 and the corresponding HB energies were further performed with the density functional theory (DFT) [B3LYP/6-31G*] method. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Insecticidal Constituents and Activity of Alkaloids from Cynanchum mongolicum
Molecules 2015, 20(9), 17483-17492; doi:10.3390/molecules200917483
Received: 16 July 2015 / Revised: 18 August 2015 / Accepted: 25 August 2015 / Published: 21 September 2015
Cited by 3 | PDF Full-text (827 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they
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Based on MS and NMR data and bioassay-guided tracing, three insecticidal alkaloids I, II and III from Cynanchum mongolicum were identified to be antofine N-oxide, antofine and tylophorine. Alkaloid I was more toxic than alkaloids II and III, but they were less active against Spodoptera litura than total alkaloids. The contact toxicity from these alkaloids against the aphid Lipaphis erysimi was significant, as the 24 h-LC50 values of alkaloids I, II, III and total alkaloids were 292.48, 367.21, 487.791 and 163.52 mg/L, respectively. The development disruption of S. litura larvae was tested, the pupation and emergence rates of S. litura decreased and the acute mortality of S. litura increased significantly by day 3 after being injected in their body cavity with 10–40 mg/L of total alkaloid. The ecdysone titer of treated S. litura larvae and prepupae declined with increasing alkaloid concentration. The alkaloids of Cynanchum mongolicum are potential insect growth inhibitors. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Quantitative Structure–Property Relationship (QSPR) Models for a Local Quantum Descriptor: Investigation of the 4- and 3-Substituted-Cinnamic Acid Esterification
Molecules 2015, 20(9), 17493-17510; doi:10.3390/molecules200917493
Received: 27 June 2015 / Revised: 12 September 2015 / Accepted: 15 September 2015 / Published: 22 September 2015
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Abstract
In this work, the theoretical description of the 4- and 3-substituted-cinnamic acid esterification with different electron donating and electron withdrawing groups was performed at the B3LYP and M06-2X levels, as a two-step process: the O-protonation and the nucleophile attack by ethanol. In
[...] Read more.
In this work, the theoretical description of the 4- and 3-substituted-cinnamic acid esterification with different electron donating and electron withdrawing groups was performed at the B3LYP and M06-2X levels, as a two-step process: the O-protonation and the nucleophile attack by ethanol. In parallel, an experimental work devoted to the synthesis and characterization of the substituted-cinnamate esters has also been performed. In order to quantify the substituents effects, quantitative structure–property relationship (QSPR) models based on the atomic charges, Fukui functions and the Frontier Effective-for-Reaction Molecular Orbitals (FERMO) energies were investigated. In fact, the Fukui functions, ƒ+C and ƒO, indicated poor correlations for each individual step, and in contrast with the general literature, the O-protonation step is affected both by the FERMO energies and the O-charges of the carbonyl group. Since the process was shown to not be totally described by either charge- or frontier-orbitals, it is proposed to be frontier-charge-miscere controlled. Moreover, the observed trend for the experimental reaction yields suggests that the electron withdrawing groups favor the reaction and the same was observed for Step 2, which can thus be pointed out as the determining step. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Electrical Properties of Multi-Pyrene/Porphyrin-Dendrimers
Molecules 2015, 20(9), 17533-17543; doi:10.3390/molecules200917533
Received: 28 July 2015 / Revised: 8 September 2015 / Accepted: 15 September 2015 / Published: 22 September 2015
Cited by 1 | PDF Full-text (1501 KB) | HTML Full-text | XML Full-text
Abstract
Dendrimers bearing pyrene donor groups have been obtained and act as efficient light-harvesting antennae capable of transferring light energy through space from their periphery to their core. The light-harvesting ability increases with each generation due to an increase in the number of peripheral
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Dendrimers bearing pyrene donor groups have been obtained and act as efficient light-harvesting antennae capable of transferring light energy through space from their periphery to their core. The light-harvesting ability increases with each generation due to an increase in the number of peripheral pyrenes. In order to evaluate the photovoltaic properties of the compounds, thermal evaporated thin films were produced and the voltage response in the presence of visible light was obtained. The energy transfer efficiency was found to be almost quantitative for the first and second generations. The dendrimers have the potential to become integral components of molecular photonic devices. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
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Open AccessArticle Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides
Molecules 2015, 20(9), 17544-17556; doi:10.3390/molecules200917544
Received: 29 July 2015 / Revised: 9 September 2015 / Accepted: 17 September 2015 / Published: 22 September 2015
Cited by 5 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1); 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2); and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3); together with six known
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Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1); 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2); and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3); together with six known diterpenes henryin (4); kamebanin (5); reniformin C (6); kamebacetal A (7); kamebacetal B (8); and oridonin (9). The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09–8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31–2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Antiaging Properties of Andrographis paniculata by Activation Epidermal Cell Stemness
Molecules 2015, 20(9), 17557-17569; doi:10.3390/molecules200917557
Received: 28 August 2015 / Revised: 16 September 2015 / Accepted: 17 September 2015 / Published: 22 September 2015
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Abstract
Andrographis paniculata (A. paniculata, Chuanxinlian), a medicinal herb with an extremely bitter taste that is native to China and other parts of Southeast Asia, possesses immense therapeutic value; however, its therapeutic properties have rarely been applied in the field of
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Andrographis paniculata (A. paniculata, Chuanxinlian), a medicinal herb with an extremely bitter taste that is native to China and other parts of Southeast Asia, possesses immense therapeutic value; however, its therapeutic properties have rarely been applied in the field of skin care. In this study, we investigated the effect of an A. paniculata extract (APE) on human epidermal stem cells (EpSCs), and confirmed its anti-aging effect through in vitro, ex vivo, and in vivo study. An MTT assay was used to determine cell proliferation. A flow cytometric analysis, with propidium iodide, was used to evaluate the cell cycle. The expression of integrin β1 (CD29), the stem cell marker, was detected with antibodies, using flow cytometry in vitro, and immunohistochemical assays in ex vivo. Type 1 collagen and VEGF (vascular endothelial growth factor) were measured using an enzyme-linked immunosorbent assay (ELISA). During the clinical study, skin hydration, elasticity, wrinkling, sagging, and dermal density were evaluated before treatment and at four and eight weeks after the treatment with the test product (containing the APE) on the face. The proliferation of the EpSCs, treated with the APE, increased significantly. In the cell cycle analysis, the APE increased the G2/M and S stages in a dose-dependent manner. The expression of integrin β1, which is related to epidermal progenitor cell expansion, was up-regulated in the APE-treated EpSCs and skin explants. In addition, the production of VEGF in the EpSCs increased significantly in response to the APE treatment. Consistent with these results, the VEGF and APE-treated EpSCs conditioned medium enhanced the Type 1 collagen production in normal human fibroblasts (NHFs). In the clinical study, the APE improved skin hydration, dermal density, wrinkling, and sagging significantly. Our findings revealed that the APE promotes a proliferation of EpSCs, through the up-regulation of the integrin β1 and VEGF expression. The VEGF might affect the collagen synthesis of NHF as a paracrine factor. Clinical studies further suggested that treatment with formulations containing APE confers anti-aging benefits. Based on these results, we suggest that APE may be introduced as a possible anti-aging agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension
Molecules 2015, 20(9), 17570-17584; doi:10.3390/molecules200917570
Received: 7 July 2015 / Revised: 8 September 2015 / Accepted: 10 September 2015 / Published: 22 September 2015
Cited by 5 | PDF Full-text (1347 KB) | HTML Full-text | XML Full-text
Abstract
Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L.) bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from
[...] Read more.
Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L.) bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins) isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M) in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester) or indomethacin (both 10−5 M), respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension. Full article
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Open AccessArticle Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents
Molecules 2015, 20(9), 17585-17600; doi:10.3390/molecules200917585
Received: 30 July 2015 / Revised: 17 September 2015 / Accepted: 17 September 2015 / Published: 23 September 2015
PDF Full-text (733 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) test. The activity experimental study showed that 2,2-dipropyl-
[...] Read more.
A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) test. The activity experimental study showed that 2,2-dipropyl-N1-(4-sulfamoylphenyl)malonamide (18b) had the lowest median effective dose (ED50) of 16.36 mg/kg in MES test, and 2,2-dimethyl-N-(4-sulfamoylphenyl)cyclopropane-1,1-dicarboxamide (12c) had the lowest ED50 of 22.50 mg/kg in scPTZ test, which resulted in the protective indexe (PI) of 24.8 and 20.4, respectively. These promising data suggest the new compounds have good potential as new class of anticonvulsant agents with high effectiveness and low toxicity for the treatment of epilepsy. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle The Application of Template Selectophores for the Preparation of Molecularly Imprinted Polymers
Molecules 2015, 20(9), 17601-17613; doi:10.3390/molecules200917601
Received: 11 July 2015 / Revised: 20 August 2015 / Accepted: 28 August 2015 / Published: 23 September 2015
Cited by 5 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Molecularly imprinted polymers are versatile materials with wide application scope for the detection, capture and separation of specific compounds present in complex feed stocks. A major challenge associated with their preparation has been the need to sacrifice one mole equivalent of the template
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Molecularly imprinted polymers are versatile materials with wide application scope for the detection, capture and separation of specific compounds present in complex feed stocks. A major challenge associated with their preparation has been the need to sacrifice one mole equivalent of the template molecule to generate the complementary polymer cavities that selectively bind the target molecule. Moreover, template molecules can often be difficult to synthesise, expensive or lack stability. In this study, we describe a new approach, directed at the use of synthetic selectophores, chosen as readily prepared and low cost structural analogues with recognition groups in similar three-dimensional arrangements as found in the target molecule. To validate the approach, a comparative study of selectophores related to the polyphenolic compound (E)-resveratrol has been undertaken using traditional and green chemical synthetic approaches. These molecular mimic compounds were employed as polymer templates and also as binding analytes to interrogate the recognition sites associated with the molecularly imprinted polymers. Importantly, the study confirms that the use of selectophores has the potential to confer practical advantages, including access to more efficient methods for selection and preparation of suitable template molecules with a broader range of molecular diversity, as well as delivering imprinted polymers capable of recognizing the target compound and structurally related products. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
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Open AccessArticle Antibacterial and Antitumor Activities of Biscoumarin and Dihydropyran Derivatives
Molecules 2015, 20(9), 17614-17626; doi:10.3390/molecules200917614
Received: 7 August 2015 / Revised: 11 September 2015 / Accepted: 14 September 2015 / Published: 23 September 2015
Cited by 2 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
A novel series of biscoumarin (14) and dihydropyran (513) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four
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A novel series of biscoumarin (14) and dihydropyran (513) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds, 3, 7, 9 and 11, confirmed the structures of these compounds. Compounds 14 showed the most potent antitumor activity among the total 13 derivatives; especially for compounds 1 and 2, they also emerged as promising antibacterial members with better antibacterial activity. In addition, the results of density functional theory (DFT) showed that compared with compounds 3 and 4, biscoumarins 1 and 2 had lower intramolecular hydrogen bonds (HB) energy in their structures. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Dichlorinated and Brominated Rugulovasines, Ergot Alkaloids Produced by Talaromyces wortmannii
Molecules 2015, 20(9), 17627-17644; doi:10.3390/molecules200917627
Received: 1 August 2015 / Revised: 17 September 2015 / Accepted: 21 September 2015 / Published: 23 September 2015
Cited by 1 | PDF Full-text (1241 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
UHPLC-DAD-HRMS based dereplication guided the detection of new halogenated alkaloids co-produced by Talaromyces wortmannii. From the fungal growth in large scale, the epimers 2,8-dichlororugulovasines A and B were purified and further identified by means of a HPLC-SPE/NMR hyphenated system. Brominated rugulovasines were
[...] Read more.
UHPLC-DAD-HRMS based dereplication guided the detection of new halogenated alkaloids co-produced by Talaromyces wortmannii. From the fungal growth in large scale, the epimers 2,8-dichlororugulovasines A and B were purified and further identified by means of a HPLC-SPE/NMR hyphenated system. Brominated rugulovasines were also detected when the microbial incubation medium was supplemented with bromine sources. Studies from 1D/2D NMR and HRMS spectroscopy data allowed the structural elucidation of the dichlorinated compounds, while tandem MS/HRMS data analysis supported the rationalization of brominated congeners. Preliminary genetic studies revealed evidence that FADH2 dependent halogenase can be involved in the biosynthesis of the produced halocompounds. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Comparative Incorporation of PNA into DNA Nanostructures
Molecules 2015, 20(9), 17645-17658; doi:10.3390/molecules200917645
Received: 6 August 2015 / Revised: 13 September 2015 / Accepted: 21 September 2015 / Published: 23 September 2015
Cited by 1 | PDF Full-text (2450 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
DNA has shown great promise as a building material for self-assembling nanoscale structures. To further develop the potential of this technology, more methods are needed for functionalizing DNA-based nanostructures to increase their chemical diversity. Peptide nucleic acid (PNA) holds great promise for realizing
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DNA has shown great promise as a building material for self-assembling nanoscale structures. To further develop the potential of this technology, more methods are needed for functionalizing DNA-based nanostructures to increase their chemical diversity. Peptide nucleic acid (PNA) holds great promise for realizing this goal, as it conveniently allows for inclusion of both amino acids and peptides in nucleic acid-based structures. In this work, we explored incorporation of a positively charged PNA within DNA nanostructures. We investigated the efficiency of annealing a lysine-containing PNA probe with complementary, single-stranded DNA sequences within nanostructures, as well as the efficiency of duplex invasion and its dependence on salt concentration. Our results show that PNA allows for toehold-free strand displacement and that incorporation yield depends critically on binding site geometry. These results provide guidance for the design of PNA binding sites on nucleic acid nanostructures with an eye towards optimizing fabrication yield. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Discovery and Structure-Based Optimization of 6-Bromotryptamine Derivatives as Potential 5-HT2A Receptor Antagonists
Molecules 2015, 20(9), 17675-17683; doi:10.3390/molecules200917675
Received: 23 August 2015 / Revised: 17 September 2015 / Accepted: 21 September 2015 / Published: 23 September 2015
PDF Full-text (1182 KB) | HTML Full-text | XML Full-text
Abstract
5-Hydroxytryptamine type 2A (5-HT2A) receptor is an important target for developing innovative antipsychotic agents in neuropsychiatric disorder therapies. To search for 5-HT2A receptor antagonists, a new indole alkaloid termed 6-bromo-N-propionyltryptamine (1), together with one known homologue
[...] Read more.
5-Hydroxytryptamine type 2A (5-HT2A) receptor is an important target for developing innovative antipsychotic agents in neuropsychiatric disorder therapies. To search for 5-HT2A receptor antagonists, a new indole alkaloid termed 6-bromo-N-propionyltryptamine (1), together with one known homologue 6-bromo-N-acetyltryptamine (2) were isolated and identified from a marine bacterium Pseudoalteromonas rubra QD1-2. Compound 1 with an N-propionyl side chain exhibited stronger 5-HT2A receptor antagonist activity than that of N-acetyl derivative (2), indicating that 6-bromotryptamine analogues with a longer chain acyl group perhaps displayed a more potent capacity to the target. Therefore, a series of new 6-bromotryptamine analogues (37) with different chain length of the acyl group (C4–C8) were prepared and evaluated activity against 5-HT2A receptor. Remarkably, 6-bromo-N-hexanoyltryptamine (5) displayed the most effective inhibitory activity, which was 5-fold stronger than that of the parent compound 1 and showed 70% efficacy of the positive control (ketanserin tartrate). Full article
(This article belongs to the Section Natural Products)

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Open AccessReview Experimental and Theoretical Studies in Hydrogen-Bonding Organocatalysis
Molecules 2015, 20(9), 15500-15524; doi:10.3390/molecules200915500
Received: 31 July 2015 / Revised: 14 August 2015 / Accepted: 17 August 2015 / Published: 26 August 2015
Cited by 11 | PDF Full-text (2197 KB) | HTML Full-text | XML Full-text
Abstract
Chiral thioureas and squaramides are among the most prominent hydrogen-bond bifunctional organocatalysts now extensively used for various transformations, including aldol, Michael, Mannich and Diels-Alder reactions. More importantly, the experimental and computational study of the mode of activation has begun to attract considerable attention.
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Chiral thioureas and squaramides are among the most prominent hydrogen-bond bifunctional organocatalysts now extensively used for various transformations, including aldol, Michael, Mannich and Diels-Alder reactions. More importantly, the experimental and computational study of the mode of activation has begun to attract considerable attention. Various experimental, spectroscopic and calculation methods are now frequently used, often as an integrated approach, to establish the reaction mechanism, the mode of activation or explain the stereochemical outcome of the reaction. This article comprises several case studies, sorted according to the method used in their study. The aim of this review is to give the investigators an overview of the methods currently utilized for mechanistic investigations in hydrogen-bonding organocatalysis. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessReview Wheat Bran Phenolic Acids: Bioavailability and Stability in Whole Wheat-Based Foods
Molecules 2015, 20(9), 15666-15685; doi:10.3390/molecules200915666
Received: 29 July 2015 / Revised: 20 August 2015 / Accepted: 21 August 2015 / Published: 28 August 2015
Cited by 9 | PDF Full-text (982 KB) | HTML Full-text | XML Full-text
Abstract
Wheat bran is generally considered a byproduct of the flour milling industry, but it is a great source of fibers, minerals, and antioxidants that are important for human health. Phenolic acids are a specific class of wheat bran components that may act as
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Wheat bran is generally considered a byproduct of the flour milling industry, but it is a great source of fibers, minerals, and antioxidants that are important for human health. Phenolic acids are a specific class of wheat bran components that may act as antioxidants to prevent heart disease and to lower the incidence of colon cancer. Moreover, phenolic acids have anti-inflammatory properties that are potentially significant for the promotion of gastrointestinal health. Evidence on the beneficial effects of phenolic acids as well as of other wheat bran components is encouraging the use of wheat bran as an ingredient of functional foods. After an overview of the chemistry, function, and bioavailability of wheat phenolic acids, the discussion will focus on how technologies can allow the formulation of new, functional whole wheat products with enhanced health-promoting value and safety without renouncing the good-tasting standards that are required by consumers. Finally, this review summarizes the latest studies about the stability of phenolic acids in wheat foods fortified by the addition of wheat bran, pearled fractions, or wheat bran extracts. Full article
Open AccessReview Enantioselective Cycloaddition Reactions Catalyzed by BINOL-Derived Phosphoric Acids and N-Triflyl Phosphoramides: Recent Advances
Molecules 2015, 20(9), 16103-16126; doi:10.3390/molecules200916103
Received: 20 July 2015 / Revised: 22 August 2015 / Accepted: 28 August 2015 / Published: 3 September 2015
Cited by 11 | PDF Full-text (1356 KB) | HTML Full-text | XML Full-text
Abstract
Over the last several years there has been a huge increase in the development and applications of new efficient organocatalysts for enantioselective pericyclic reactions, which represent one of the most powerful types of organic transformations. Among these processes are cycloaddition reactions (e.g., [3+2];
[...] Read more.
Over the last several years there has been a huge increase in the development and applications of new efficient organocatalysts for enantioselective pericyclic reactions, which represent one of the most powerful types of organic transformations. Among these processes are cycloaddition reactions (e.g., [3+2]; formal [3+3]; [4+2]; vinylogous [4+2] and 1,3-dipolar cycloadditions), which belong to the most utilized reactions in organic synthesis of complex nitrogen- and oxygen-containing heterocyclic molecules. This review presents the breakthrough realized in this field using chiral BINOL-derived phosphoric acids and N-triflyl phosphoramide organocatalysts. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessReview Review of Platensimycin and Platencin: Inhibitors of β-Ketoacyl-acyl Carrier Protein (ACP) Synthase III (FabH)
Molecules 2015, 20(9), 16127-16141; doi:10.3390/molecules200916127
Received: 9 July 2015 / Revised: 24 August 2015 / Accepted: 28 August 2015 / Published: 3 September 2015
Cited by 3 | PDF Full-text (1964 KB) | HTML Full-text | XML Full-text
Abstract
Platensimycin and platencin were successively discovered from the strain Streptomyces platensis through systematic screening. These natural products have been defined as promising agents for fighting multidrug resistance in bacteria by targeting type II fatty acid synthesis with slightly different mechanisms. Bioactivity studies have
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Platensimycin and platencin were successively discovered from the strain Streptomyces platensis through systematic screening. These natural products have been defined as promising agents for fighting multidrug resistance in bacteria by targeting type II fatty acid synthesis with slightly different mechanisms. Bioactivity studies have shown that platensimycin and platencin offer great potential to inhibit many resistant bacteria with no cross-resistance or toxicity observed in vivo. This review summarizes the general information on platensimycin and platencin, including antibacterial and self-resistant mechanisms. Furthermore, the total synthesis pathways of platensimycin and platencin and their analogues from recent studies are presented. Full article
Open AccessReview Methods to Increase the Metabolic Stability of 18F-Radiotracers
Molecules 2015, 20(9), 16186-16220; doi:10.3390/molecules200916186
Received: 16 June 2015 / Revised: 20 August 2015 / Accepted: 26 August 2015 / Published: 3 September 2015
Cited by 8 | PDF Full-text (1526 KB) | HTML Full-text | XML Full-text
Abstract
The majority of pharmaceuticals and other organic compounds incorporating radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Metabolic degradation of these drugs is commonly caused by a system of enzymes of low substrate specificity requirement, which is
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The majority of pharmaceuticals and other organic compounds incorporating radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Metabolic degradation of these drugs is commonly caused by a system of enzymes of low substrate specificity requirement, which is present mainly in the liver, but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo highlighting the importance of their structure. Often in practice, such biologically active molecules exhibit these properties in vitro, but fail during in vivo studies due to obtaining an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds never see application due to their lack of stability. One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of 18F-radiotracers goes along with the cleavage of the C-F bond and with the rejection of [18F]fluoride mostly combined with high background and accumulation in the skeleton. This review deals with the impact of radiodefluorination and with approaches to stabilize the C-F bond to avoid the cleavage between fluorine and carbon. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
Open AccessReview The Biosynthetic Pathways of Tanshinones and Phenolic Acids in Salvia miltiorrhiza
Molecules 2015, 20(9), 16235-16254; doi:10.3390/molecules200916235
Received: 19 July 2015 / Accepted: 24 August 2015 / Published: 8 September 2015
Cited by 13 | PDF Full-text (2149 KB) | HTML Full-text | XML Full-text
Abstract
Secondary metabolites from plants play key roles in human medicine and chemical industries. Due to limited accumulation of secondary metabolites in plants and their important roles, characterization of key enzymes involved in biosynthetic pathway will enable metabolic engineering or synthetic biology to improve
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Secondary metabolites from plants play key roles in human medicine and chemical industries. Due to limited accumulation of secondary metabolites in plants and their important roles, characterization of key enzymes involved in biosynthetic pathway will enable metabolic engineering or synthetic biology to improve or produce the compounds in plants or microorganisms, which provides an alternative for production of these valuable compounds. Salvia miltiorrhiza, containing tanshinones and phenolic acids as its active compounds, has been widely used for the treatment of cardiovascular and cerebrovascular diseases. The biosynthetic analysis of secondary metabolites in S. miltiorrhiza has made great progress due to the successful genetic transformation system, simplified hairy roots system, and high-throughput sequencing. The cloned genes in S. miltiorrhiza had provided references for functional characterization of the post-modification steps involved in biosynthesis of tanshinones and phenolic acids, and further utilization of these steps in metabolic engineering. The strategies used in these studies could provide solid foundation for elucidation of biosynthetic pathways of diterpenoids and phenolic acids in other species. The present review systematically summarizes recent advances in biosynthetic pathway analysis of tanshinones and phenolic acids as well as synthetic biology and metabolic engineering applications of the rate-limiting genes involved in the secondary metabolism in S. miltiorrhiza. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Dihydro-5,6-dehydrokavain (DDK) from Alpinia zerumbet: Its Isolation, Synthesis, and Characterization
Molecules 2015, 20(9), 16306-16319; doi:10.3390/molecules200916306
Received: 9 June 2015 / Revised: 14 August 2015 / Accepted: 20 August 2015 / Published: 9 September 2015
Cited by 3 | PDF Full-text (761 KB) | HTML Full-text | XML Full-text
Abstract
Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its
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Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its α-lactone ring, DDK belongs to the large chemical group of kavalactones, which are also found in kava (Piper methysticum), another herbal medicine; DDK is characterized by a double-bond linkage at positions 5,6 and the absence of a double-bond linkage at positions 7,8. This dissociates DDK from other kavalactones with their linkages at positions 7,8 and 5,6 that are both either completely saturated or unsaturated, or may have an unsaturated bond at the position 7,8 as well as a saturated bond at the position 5,6. DDK is easily identified and quantified by HPLC and GC. DDK contents in fresh leaves, stems and rhizomes range from 80 to 410 mg/g, requiring solvent extraction procedures to ensure high DDK yield. This is best achieved by hexane extraction from fresh rhizomes that were previously boiled in water, allowing DDK yields of up to 424 mg/g. Successful synthesis of DDK can be achieved by asymmetric pathways, whereas its simple chemical structure facilitates the synthesis of DDK derivatives by HCl hydrolysis. Thus, all synthesized products may be used for various commercial purposes, including the potential development of promising antiobesity pharmaceutical drugs, preparation of specific and safe dietary supplements, and use as effective natural herbicides or fungicides. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Anti-Enterovirus 71 Agents of Natural Products
Molecules 2015, 20(9), 16320-16333; doi:10.3390/molecules200916320
Received: 1 August 2015 / Revised: 18 August 2015 / Accepted: 26 August 2015 / Published: 9 September 2015
Cited by 3 | PDF Full-text (799 KB) | HTML Full-text | XML Full-text
Abstract
This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds
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This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Small Molecule Targeting of Protein–Protein Interactions through Allosteric Modulation of Dynamics
Molecules 2015, 20(9), 16435-16445; doi:10.3390/molecules200916435
Received: 7 August 2015 / Revised: 6 September 2015 / Accepted: 8 September 2015 / Published: 10 September 2015
Cited by 3 | PDF Full-text (667 KB) | HTML Full-text | XML Full-text
Abstract
The protein–protein interaction (PPI) target class is particularly challenging, but offers potential for “first in class” therapies. Most known PPI small molecules are orthosteric inhibitors but many PPI sites may be fundamentally intractable to this approach. One potential alternative is to consider more
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The protein–protein interaction (PPI) target class is particularly challenging, but offers potential for “first in class” therapies. Most known PPI small molecules are orthosteric inhibitors but many PPI sites may be fundamentally intractable to this approach. One potential alternative is to consider more attractive, remote small molecule pockets; however, on the whole, allostery is poorly understood and difficult to discover and develop. Here we review the literature in order to understand the basis for allostery, especially as it can apply to PPIs. We suggest that the upfront generation of sophisticated and experimentally validated dynamic models of target proteins can aid in target choice and strategy for allosteric intervention to produce the required functional effect. Full article
(This article belongs to the Special Issue Small Molecules Modulation in Protein-Protein Interactions)
Open AccessReview Nanoparticles Biosynthesized by Fungi and Yeast: A Review of Their Preparation, Properties, and Medical Applications
Molecules 2015, 20(9), 16540-16565; doi:10.3390/molecules200916540
Received: 17 June 2015 / Revised: 6 August 2015 / Accepted: 18 August 2015 / Published: 11 September 2015
Cited by 16 | PDF Full-text (2295 KB) | HTML Full-text | XML Full-text
Abstract
In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. Among the many possible bio resources, biologically active products from fungi and yeast represent excellent scaffolds for
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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. Among the many possible bio resources, biologically active products from fungi and yeast represent excellent scaffolds for this purpose. Since fungi and yeast are very effective secretors of extracellular enzymes and number of species grow fast and therefore culturing and keeping them in the laboratory are very simple. They are able to produce metal nanoparticles and nanostructure via reducing enzyme intracellularly or extracellularly. The focus of this review is the application of fungi and yeast in the green synthesis of inorganic nanoparticles. Meanwhile the domain of biosynthesized nanoparticles is somewhat novel; the innovative uses in nano medicine in different areas including the delivery of drug, cancer therapy, antibacterial, biosensors, and MRI and medical imaging are reviewed. The proposed signaling pathways of nanoparticles induced apoptosis in cancerous cells and anti-angiogenesis effects also are reviewed. In this article, we provide a short summary of the present study universally on the utilization of eukaryotes like yeast and fungi in the biosynthesis of nanoparticles (NPs) and their uses. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessReview Generation of Aptamers with an Expanded Chemical Repertoire
Molecules 2015, 20(9), 16643-16671; doi:10.3390/molecules200916643
Received: 13 August 2015 / Revised: 28 August 2015 / Accepted: 1 September 2015 / Published: 14 September 2015
Cited by 36 | PDF Full-text (1388 KB) | HTML Full-text | XML Full-text
Abstract
The enzymatic co-polymerization of modified nucleoside triphosphates (dN*TPs and N*TPs) is a versatile method for the expansion and exploration of expanded chemical space in SELEX and related combinatorial methods of in vitro selection. This strategy can be exploited to generate aptamers with improved
[...] Read more.
The enzymatic co-polymerization of modified nucleoside triphosphates (dN*TPs and N*TPs) is a versatile method for the expansion and exploration of expanded chemical space in SELEX and related combinatorial methods of in vitro selection. This strategy can be exploited to generate aptamers with improved or hitherto unknown properties. In this review, we discuss the nature of the functionalities appended to nucleoside triphosphates and their impact on selection experiments. The properties of the resulting modified aptamers will be described, particularly those integrated in the fields of biomolecular diagnostics, therapeutics, and in the expansion of genetic systems (XNAs). Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
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Open AccessReview Recent Developments in Chemical Synthesis with Biocatalysts in Ionic Liquids
Molecules 2015, 20(9), 16788-16816; doi:10.3390/molecules200916788
Received: 11 July 2015 / Revised: 24 August 2015 / Accepted: 9 September 2015 / Published: 15 September 2015
Cited by 24 | PDF Full-text (1825 KB) | HTML Full-text | XML Full-text
Abstract
Over the past decade, a variety of ionic liquids have emerged as greener solvents for use in the chemical manufacturing industries. Their unique properties have attracted the interest of chemists worldwide to employ them as replacement for conventional solvents in a diverse range
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Over the past decade, a variety of ionic liquids have emerged as greener solvents for use in the chemical manufacturing industries. Their unique properties have attracted the interest of chemists worldwide to employ them as replacement for conventional solvents in a diverse range of chemical transformations including biotransformations. Biocatalysts are often regarded as green catalysts compared to conventional chemical catalysts in organic synthesis owing to their properties of low toxicity, biodegradability, excellent selectivity and good catalytic performance under mild reaction conditions. Similarly, a selected number of specific ionic liquids can be considered as greener solvents superior to organic solvents owing to their negligible vapor pressure, low flammability, low toxicity and ability to dissolve a wide range of organic and biological substances, including proteins. A combination of biocatalysts and ionic liquids thus appears to be a logical and promising opportunity for industrial use as an alternative to conventional organic chemistry processes employing organic solvents. This article provides an overview of recent developments in this field with special emphasis on the application of more sustainable enzyme-catalyzed reactions and separation processes employing ionic liquids, driven by advances in fundamental knowledge, process optimization and industrial deployment. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
Open AccessReview Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine’s Tool Box
Molecules 2015, 20(9), 16852-16891; doi:10.3390/molecules200916852
Received: 19 June 2015 / Revised: 8 September 2015 / Accepted: 9 September 2015 / Published: 16 September 2015
Cited by 42 | PDF Full-text (1892 KB) | HTML Full-text | XML Full-text
Abstract
The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many
[...] Read more.
The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles. Full article
(This article belongs to the collection Heterocyclic Compounds)
Open AccessReview Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy
Molecules 2015, 20(9), 16987-17015; doi:10.3390/molecules200916987
Received: 11 August 2015 / Revised: 9 September 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
Cited by 13 | PDF Full-text (2031 KB) | HTML Full-text | XML Full-text
Abstract
To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in
[...] Read more.
To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional “only one function” to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof. Full article
(This article belongs to the collection Nanomedicine)
Open AccessReview Novel Metal Nanomaterials and Their Catalytic Applications
Molecules 2015, 20(9), 17070-17092; doi:10.3390/molecules200917070
Received: 13 July 2015 / Revised: 27 August 2015 / Accepted: 31 August 2015 / Published: 17 September 2015
Cited by 13 | PDF Full-text (3013 KB) | HTML Full-text | XML Full-text
Abstract
In the rapidly developing areas of nanotechnology, nano-scale materials as heterogeneous catalysts in the synthesis of organic molecules have gotten more and more attention. In this review, we will summarize the synthesis of several new types of noble metal nanostructures (FePt@Cu nanowires, Pt@Fe
[...] Read more.
In the rapidly developing areas of nanotechnology, nano-scale materials as heterogeneous catalysts in the synthesis of organic molecules have gotten more and more attention. In this review, we will summarize the synthesis of several new types of noble metal nanostructures (FePt@Cu nanowires, Pt@Fe2O3 nanowires and bimetallic Pt@Ir nanocomplexes; Pt-Au heterostructures, Au-Pt bimetallic nanocomplexes and Pt/Pd bimetallic nanodendrites; Au nanowires, CuO@Ag nanowires and a series of Pd nanocatalysts) and their new catalytic applications in our group, to establish heterogeneous catalytic system in “green” environments. Further study shows that these materials have a higher catalytic activity and selectivity than previously reported nanocrystal catalysts in organic reactions, or show a superior electro-catalytic activity for the oxidation of methanol. The whole process might have a great impact to resolve the energy crisis and the environmental crisis that were caused by traditional chemical engineering. Furthermore, we hope that this article will provide a reference point for the noble metal nanomaterials’ development that leads to new opportunities in nanocatalysis. Full article
(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)
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Open AccessReview Editorial of Special Issue Ruthenium Complex: The Expanding Chemistry of the Ruthenium Complexes
Molecules 2015, 20(9), 17244-17274; doi:10.3390/molecules200917244
Received: 6 August 2015 / Revised: 9 September 2015 / Accepted: 11 September 2015 / Published: 18 September 2015
Cited by 16 | PDF Full-text (763 KB) | HTML Full-text | XML Full-text
Abstract
Recent trends in Ru complex chemistry are surveyed with emphasis on the development of anticancer drugs and applications in catalysis, polymers, materials science and nanotechnology. Full article
(This article belongs to the Special Issue Ruthenium Complex)
Open AccessReview Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Health
Molecules 2015, 20(9), 17339-17361; doi:10.3390/molecules200917339
Received: 31 July 2015 / Revised: 2 September 2015 / Accepted: 9 September 2015 / Published: 18 September 2015
Cited by 20 | PDF Full-text (1666 KB) | HTML Full-text | XML Full-text
Abstract
A growing body of evidence highlights the close association between nutrition and human health. Fat is an essential macronutrient, and vegetable oils, such as palm oil, are widely used in the food industry and highly represented in the human diet. Palmitic acid, a
[...] Read more.
A growing body of evidence highlights the close association between nutrition and human health. Fat is an essential macronutrient, and vegetable oils, such as palm oil, are widely used in the food industry and highly represented in the human diet. Palmitic acid, a saturated fatty acid, is the principal constituent of refined palm oil. In the last few decades, controversial studies have reported potential unhealthy effects of palm oil due to the high palmitic acid content. In this review we provide a concise and comprehensive update on the functional role of palm oil and palmitic acid in the development of obesity, type 2 diabetes mellitus, cardiovascular diseases and cancer. The atherogenic potential of palmitic acid and its stereospecific position in triacylglycerols are also discussed. Full article
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Open AccessReview Metabolic and Microbial Modulation of the Large Intestine Ecosystem by Non-Absorbed Diet Phenolic Compounds: A Review
Molecules 2015, 20(9), 17429-17468; doi:10.3390/molecules200917429
Received: 4 August 2015 / Revised: 31 August 2015 / Accepted: 11 September 2015 / Published: 18 September 2015
Cited by 17 | PDF Full-text (1438 KB) | HTML Full-text | XML Full-text
Abstract
Phenolic compounds represent a diverse group of phytochemicals whose intake is associated with a wide spectrum of health benefits. As consequence of their low bioavailability, most of them reach the large intestine where, mediated by the action of local microbiota, a series of
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Phenolic compounds represent a diverse group of phytochemicals whose intake is associated with a wide spectrum of health benefits. As consequence of their low bioavailability, most of them reach the large intestine where, mediated by the action of local microbiota, a series of related microbial metabolites are accumulated. In the present review, gut microbial transformations of non-absorbed phenolic compounds are summarized. Several studies have reached a general consensus that unbalanced diets are associated with undesirable changes in gut metabolism that could be detrimental to intestinal health. In terms of explaining the possible effects of non-absorbed phenolic compounds, we have also gathered information regarded their influence on the local metabolism. For this purpose, a number of issues are discussed. Firstly, we consider the possible implications of phenolic compounds in the metabolism of colonic products, such as short chain fatty acids (SCFA), sterols (cholesterol and bile acids), and microbial products of non-absorbed proteins. Due to their being recognized as affective antioxidant and anti-inflammatory agents, the ability of phenolic compounds to counteract or suppress pro-oxidant and/or pro-inflammatory responses, triggered by bowel diseases, is also presented. The modulation of gut microbiota through dietetic maneuvers including phenolic compounds is also commented on. Although the available data seems to assume positive effects in terms of gut health protection, it is still insufficient for solid conclusions to be extracted, basically due to the lack of human trials to confirm the results obtained by the in vitro and animal studies. We consider that more emphasis should be focused on the study of phenolic compounds, particularly in their microbial metabolites, and their power to influence different aspects of gut health. Full article
Open AccessReview G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents
Molecules 2015, 20(9), 17511-17532; doi:10.3390/molecules200917511
Received: 31 July 2015 / Revised: 10 September 2015 / Accepted: 16 September 2015 / Published: 22 September 2015
Cited by 14 | PDF Full-text (1957 KB) | HTML Full-text | XML Full-text
Abstract
Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding
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Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessReview Small-Molecule Inhibitors of the Type III Secretion System
Molecules 2015, 20(9), 17659-17674; doi:10.3390/molecules200917659
Received: 16 July 2015 / Revised: 17 September 2015 / Accepted: 18 September 2015 / Published: 23 September 2015
Cited by 7 | PDF Full-text (1060 KB) | HTML Full-text | XML Full-text
Abstract
Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS), existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess
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Drug-resistant pathogens have presented increasing challenges to the discovery and development of new antibacterial agents. The type III secretion system (T3SS), existing in bacterial chromosomes or plasmids, is one of the most complicated protein secretion systems. T3SSs of animal and plant pathogens possess many highly conserved main structural components comprised of about 20 proteins. Many Gram-negative bacteria carry T3SS as a major virulence determinant, and using the T3SS, the bacteria secrete and inject effector proteins into target host cells, triggering disease symptoms. Therefore, T3SS has emerged as an attractive target for antimicrobial therapeutics. In recent years, many T3SS-targeting small-molecule inhibitors have been discovered; these inhibitors prevent the bacteria from injecting effector proteins and from causing pathophysiology in host cells. Targeting the virulence of Gram-negative pathogens, rather than their survival, is an innovative and promising approach that may greatly reduce selection pressures on pathogens to develop drug-resistant mutations. This article summarizes recent progress in the search for promising small-molecule T3SS inhibitors that target the secretion and translocation of bacterial effector proteins. Full article
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Open AccessCorrection Lewies, A., et al. The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases. Molecules 2015, 20, 15392–15433
Molecules 2015, 20(9), 16757; doi:10.3390/molecules200916757
Received: 3 September 2015 / Accepted: 7 September 2015 / Published: 14 September 2015
Cited by 3 | PDF Full-text (601 KB) | HTML Full-text | XML Full-text
Abstract
The authors wish to make the following corrections to this paper [1]: [...] Full article
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