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Molecules, Volume 19, Issue 11 (November 2014), Pages 17066-19252

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Open AccessArticle Microemulsion System for Topical Delivery of Thai Mango Seed Kernel Extract: Development, Physicochemical Characterisation and Ex Vivo Skin Permeation Studies
Molecules 2014, 19(11), 17107-17129; doi:10.3390/molecules191117107
Received: 20 July 2014 / Revised: 16 October 2014 / Accepted: 17 October 2014 / Published: 24 October 2014
Cited by 8 | PDF Full-text (1060 KB) | HTML Full-text | XML Full-text
Abstract
A microemulsion system containing Thai mango seed kernel extract (MSKE, cultivar “Fahlun”) was developed and characterised for the purpose of topical skin delivery. The MSKE-loaded microemulsions were prepared by using the spontaneous emulsification method. Isopropyl myristate (IPM) was selected as the oil phase.
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A microemulsion system containing Thai mango seed kernel extract (MSKE, cultivar “Fahlun”) was developed and characterised for the purpose of topical skin delivery. The MSKE-loaded microemulsions were prepared by using the spontaneous emulsification method. Isopropyl myristate (IPM) was selected as the oil phase. A polyoxyethylene sorbitan monooleate and sorbitan monododecanoate (1:1, w/w) system was used as the surfactant phase; an aqueous mixture of different cosurfactants (absolute ethanol, 96.3% v/v ethanol, 1-propanol, 2-propanol or 1,2-propanediol) at a weight ratio of 1:1 was used as the aqueous phase. Among the cosurfactants studied, the 1-propanol aqueous mixture had the largest microemulsion region (48.93%) in the pseudo-ternary phase diagram. Microemulsions containing 1% MSKE demonstrated good physicochemical stability during a six-month study period at 25 ± 2 °C/60% ± 5% RH. The ex vivo skin permeation study demonstrated that the microemulsions exhibited a potent skin enhancement effect allowing MSKE to penetrate skin layers up to 60-fold higher compared with the control. Neither skin irritation nor skin corrosion was observed in ex vivo studies. The present study revealed that IPM-based microemulsion systems may be promising carriers to enhance skin penetration and delivering MSKE for topical treatment. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Carapanolides J–L from the Seeds of Carapa guianensis (Andiroba) and Their Effects on LPS-Activated NO Production
Molecules 2014, 19(11), 17130-17140; doi:10.3390/molecules191117130
Received: 5 September 2014 / Revised: 17 October 2014 / Accepted: 20 October 2014 / Published: 24 October 2014
Cited by 11 | PDF Full-text (1132 KB) | HTML Full-text | XML Full-text
Abstract
A novel gedunin and two novel phragmalin-type limonoids, named carapanolides J–L (compounds 13) as well as a known gedunin-type limonoid 4 were isolated from the seeds of Carapa guianensis (andiroba). Their structures were determined on the basis of 1D and
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A novel gedunin and two novel phragmalin-type limonoids, named carapanolides J–L (compounds 13) as well as a known gedunin-type limonoid 4 were isolated from the seeds of Carapa guianensis (andiroba). Their structures were determined on the basis of 1D and 2D NMR spectroscopy and HRFABMS. Compounds 14 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Riboflavin Accumulation and Molecular Characterization of cDNAs Encoding Bifunctional GTP Cyclohydrolase II/3,4-Dihydroxy-2-Butanone 4-Phosphate Synthase, Lumazine Synthase, and Riboflavin Synthase in Different Organs of Lycium chinense Plant
Molecules 2014, 19(11), 17141-17153; doi:10.3390/molecules191117141
Received: 25 July 2014 / Revised: 16 October 2014 / Accepted: 17 October 2014 / Published: 24 October 2014
Cited by 2 | PDF Full-text (5688 KB) | HTML Full-text | XML Full-text
Abstract
Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin adenine dinucleotide—essential cofactors for a wide variety of enzymes involving in numerous metabolic processes. In this study, a partial-length cDNA encoding bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone-4-phosphate synthase (LcRIBA), 2 full-length cDNAs encoding lumazine
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Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin adenine dinucleotide—essential cofactors for a wide variety of enzymes involving in numerous metabolic processes. In this study, a partial-length cDNA encoding bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone-4-phosphate synthase (LcRIBA), 2 full-length cDNAs encoding lumazine synthase (LcLS1 and LcLS2), and a full-length cDNA encoding riboflavin synthase (LcRS) were isolated from Lycium chinense, an important traditional medicinal plant. Sequence analyses showed that these genes exhibited high identities with their orthologous genes as well as having the same common features related to plant riboflavin biosynthetic genes. LcRIBA, like other plant RIBAs, contained a DHBPS region in its N terminus and a GCHII region in its C-terminal part. LcLSs and LcRS carried an N-terminal extension found in plant riboflavin biosynthetic genes unlike the orthologous microbial genes. Quantitative real-time polymerase chain reaction analysis showed that 4 riboflavin biosynthetic genes were constitutively expressed in all organs examined of L. chinense plants with the highest expression levels found in the leaves or red fruits. LcRIBA, which catalyzes 2 initial reactions in riboflavin biosynthetic pathway, was the highest transcript in the leaves, and hence, the richest content of riboflavin was detected in this organ. Our study might provide the basis for investigating the contribution of riboflavin in diverse biological activities of L. chinense and may facilitate the metabolic engineering of vitamin B2 in crop plants. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle 2-(1H-Benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol, a Benzimidazole Derivative, Inhibits T Cell Proliferation Involving H+/K+-ATPase Inhibition
Molecules 2014, 19(11), 17173-17186; doi:10.3390/molecules191117173
Received: 1 September 2014 / Revised: 13 October 2014 / Accepted: 21 October 2014 / Published: 24 October 2014
PDF Full-text (10515 KB) | HTML Full-text | XML Full-text
Abstract
In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation.
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In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2) production; treating IL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis, X-ray Diffraction, Thermogravimetric and DFT Analyses of Pyrimidine Derivatives
Molecules 2014, 19(11), 17187-17201; doi:10.3390/molecules191117187
Received: 25 September 2014 / Revised: 16 October 2014 / Accepted: 17 October 2014 / Published: 24 October 2014
Cited by 5 | PDF Full-text (1131 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An eco-benign synthesis of pyrimidine derivatives 2a,b containing different functional groups with different electronic character starting from nitroalkenes 1a and 2b has been described. The structures for 1a and 2a,b have been characterized by single crystal X-ray diffraction analysis.
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An eco-benign synthesis of pyrimidine derivatives 2a,b containing different functional groups with different electronic character starting from nitroalkenes 1a and 2b has been described. The structures for 1a and 2a,b have been characterized by single crystal X-ray diffraction analysis. The thermal data of the molecules pointed towards important structural aspects of their stability. The mechanism of their thermal decomposition is discussed. The thermodynamic parameters of the dissociation steps were evaluated and discussed. DFT calculations reveal that the compound 1a possesses a high calculated dipole moment value (8.28 D) which indicates its high reactivity towards its surrounding molecules. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle ROS-Mediated Cytotoxic Effect of Copper(II) Hydrazone Complexes against Human Glioma Cells
Molecules 2014, 19(11), 17202-17220; doi:10.3390/molecules191117202
Received: 25 September 2014 / Revised: 15 October 2014 / Accepted: 15 October 2014 / Published: 27 October 2014
Cited by 19 | PDF Full-text (2354 KB) | HTML Full-text | XML Full-text
Abstract
2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds
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2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and Cytotoxic Evaluation of Alkoxylated Chalcones
Molecules 2014, 19(11), 17256-17278; doi:10.3390/molecules191117256
Received: 25 July 2014 / Revised: 26 September 2014 / Accepted: 17 October 2014 / Published: 28 October 2014
Cited by 4 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of chalcones a120 bearing a 4-OMe groups on the A-ring were initially synthesized and their anticancer activities towards HepG2 cells evaluated. Subsequently, a series of chalcones b142 bearing methoxy groups at the 2' and 6'-positions of the
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A series of chalcones a120 bearing a 4-OMe groups on the A-ring were initially synthesized and their anticancer activities towards HepG2 cells evaluated. Subsequently, a series of chalcones b142 bearing methoxy groups at the 2' and 6'-positions of the B-ring were synthesized and their anticancer activities towards five human cancer cell lines (HepG2, HeLa, MCF-7, A549 and SW1990) and two non-tumoral human cell lines evaluated. The results showed that six compounds (b6, b8, b11, b16, b18, b22, b23 and b29) displayed promising activities, with compounds b22 and b29 in particular showing higher levels of activity than etoposide against all five cancer cell lines. Compound b29 showed a promising SI value compared with both HMLE and L02 (2.1–6.5 fold in HMLE and > 33 > 103.1 fold in L02, respectively). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Radical Intermediates in Photoinduced Reactions on TiO2 (An EPR Spin Trapping Study)
Molecules 2014, 19(11), 17279-17304; doi:10.3390/molecules191117279
Received: 13 August 2014 / Revised: 29 September 2014 / Accepted: 22 October 2014 / Published: 28 October 2014
Cited by 32 | PDF Full-text (779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The radical intermediates formed upon UVA irradiation of titanium dioxide suspensions in aqueous and non-aqueous environments were investigated applying the EPR spin trapping technique. The results showed that the generation of reactive species and their consecutive reactions are influenced by the solvent properties
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The radical intermediates formed upon UVA irradiation of titanium dioxide suspensions in aqueous and non-aqueous environments were investigated applying the EPR spin trapping technique. The results showed that the generation of reactive species and their consecutive reactions are influenced by the solvent properties (e.g., polarity, solubility of molecular oxygen, rate constant for the reaction of hydroxyl radicals with the solvent). The formation of hydroxyl radicals, evidenced as the corresponding spin-adducts, dominated in the irradiated TiO2 aqueous suspensions. The addition of 17O-enriched water caused changes in the EPR spectra reflecting the interaction of an unpaired electron with the 17O nucleus. The photoexcitation of TiO2 in non-aqueous solvents (dimethylsulfoxide, acetonitrile, methanol and ethanol) in the presence of 5,5-dimethyl-1-pyrroline N-oxide spin trap displayed a stabilization of the superoxide radical anions generated via electron transfer reaction to molecular oxygen, and various oxygen- and carbon-centered radicals from the solvents were generated. The character and origin of the carbon-centered spin-adducts was confirmed using nitroso spin trapping agents. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessArticle The Dynamical Behavior of the s-Trioxane Radical Cation—A Low-Temperature EPR and Theoretical Study
Molecules 2014, 19(11), 17305-17313; doi:10.3390/molecules191117305
Received: 1 September 2014 / Revised: 15 October 2014 / Accepted: 21 October 2014 / Published: 28 October 2014
PDF Full-text (1647 KB) | HTML Full-text | XML Full-text
Abstract
The radical cation of s-trioxane, radiolytically generated in a freon (CF3CCl3)matrix, was studied in the 10–140 K temperature region. Reversible changes of the EPR spectra were observed, arising from both ring puckering and ring inversion through the molecular
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The radical cation of s-trioxane, radiolytically generated in a freon (CF3CCl3) matrix, was studied in the 10–140 K temperature region. Reversible changes of the EPR spectra were observed, arising from both ring puckering and ring inversion through the molecular plane. The ESREXN program based on the Liouville density matrix equation, allowing the treatment of dynamical exchange, has been used to analyze the experimental results. Two limiting conformer structures of the s-trioxane radical cation were taken into account, namely “rigid” half-boat and averaged planar ones, differing strongly in their electron distribution. The spectrum due to the “rigid” half-boat conformer can be observed only at very low (<60 K) temperatures, when the exchange of conformers is very slow. Two transition states for interconversion by puckering and ring-inversion were identified, close in activation energy (2.3 and 3.0 kJ/mol calculated). Since the energy difference is very small, both processes set on at a comparable temperature. In the case of nearly complete equilibration (fast exchange) between six energetically equivalent structures at T > 120 K in CF3CCl3, a septet due to six equivalent protons (hfs splitting constant 5.9 mT) is observed, characteristic of the dynamically averaged planar geometry of the radical cation. DFT quantum chemical calculations and spectral simulation including intramolecular dynamical exchange support the interpretation. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
Open AccessArticle Comparison of Flavonoid Compounds in the Flavedo and Juice of Two Pummelo Cultivars (Citrus grandis L. Osbeck) from Different Cultivation Regions in China
Molecules 2014, 19(11), 17314-17328; doi:10.3390/molecules191117314
Received: 10 September 2014 / Revised: 12 October 2014 / Accepted: 13 October 2014 / Published: 28 October 2014
Cited by 5 | PDF Full-text (325 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to investigate the effect of different cultivation regions on the pattern and content of flavonoids in two pummelo cultivars (C. grandis L. Osbeck) in China. Results showed that similar patterns of flavonoids were observed in the
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The objective of this study was to investigate the effect of different cultivation regions on the pattern and content of flavonoids in two pummelo cultivars (C. grandis L. Osbeck) in China. Results showed that similar patterns of flavonoids were observed in the flavedo or juice of each pummelo cultivar from these cultivation regions, whereas the individual flavonoid content showed unique characteristics. Naringin, the predominant flavanone glycoside, showed the highest content in both flavedo and juice of C. grandis “Guanximiyu” from the Pinghe of Fujian (FJ) cultivation region compared with the Dapu of Guangdong (GD) and Nanbu of Sichuan (SC) regions. However, its content in the flavedo of C. grandis “Shatianyu” from the Pingle of Guangxi (GX) was significantly lower than in the GD and SC regions. Vicenin-2 appeared to be the dominant flavone C-glycoside in the flavedo of both cultivars, and the lowest content was observed in the flavedo of C. grandis “Guanximiyu” from the SC region. However, C. grandis “Shatianyu” contained the highest content of vicenin-2 in the flavedo from SC region. Similarly, the predominant flavone O-glucoside, rhoifolin, showed the highest content in C. grandis “Guanximiyu” from the GD and FJ regions, whereas C. grandis “Shatianyu” in SC region showed the highest content of rhoifolin. Cluster analysis suggested that genotype played a primary role in determining the flavonoid profiles of pummelo cultivars, whereas regional differences significantly affected the flavonoid distribution of pummelo cultivars potentially via affecting the direction of flavonoid accumulation in pummelo. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Bioconversion of Rebaudioside I from Rebaudioside A
Molecules 2014, 19(11), 17345-17355; doi:10.3390/molecules191117345
Received: 22 August 2014 / Revised: 3 October 2014 / Accepted: 23 October 2014 / Published: 28 October 2014
PDF Full-text (458 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
To supply the increasing demand of natural high potency sweeteners to reduce the calories in food and beverages, we have looked to steviol glycosides. In this work we report the bioconversion of rebaudioside A to rebaudioside I using a glucosyltransferase enzyme. This bioconversion
[...] Read more.
To supply the increasing demand of natural high potency sweeteners to reduce the calories in food and beverages, we have looked to steviol glycosides. In this work we report the bioconversion of rebaudioside A to rebaudioside I using a glucosyltransferase enzyme. This bioconversion reaction adds one sugar unit with a 1→3 linkage. We utilized 1D and 2D NMR spectroscopy (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY and NOESY) and mass spectral data to fully characterize rebaudioside I. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle 4-Amino-substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases
Molecules 2014, 19(11), 17356-17380; doi:10.3390/molecules191117356
Received: 18 September 2014 / Revised: 14 October 2014 / Accepted: 21 October 2014 / Published: 28 October 2014
Cited by 4 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text
Abstract
A series of N-aryl-β-alanine derivatives and diazobenzenesulfonamides containing aliphatic rings were designed, synthesized, and their binding to carbonic anhydrases (CA) I, II, VI, VII, XII, and XIII was studied by the fluorescent thermal shift assay and isothermal titration calorimetry. The results showed
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A series of N-aryl-β-alanine derivatives and diazobenzenesulfonamides containing aliphatic rings were designed, synthesized, and their binding to carbonic anhydrases (CA) I, II, VI, VII, XII, and XIII was studied by the fluorescent thermal shift assay and isothermal titration calorimetry. The results showed that 4-substituted diazobenzenesulfonamides were more potent CA binders than N-aryl-β-alanine derivatives. Most of the N-aryl-β-alanine derivatives showed better affinity for CA II while diazobenzenesulfonamides possessed nanomolar affinities towards CA I isozyme. X-ray crystallographic structures showed the modes of binding of both compound groups. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Tissue-Specific Distribution of Ginsenosides in Different Aged Ginseng and Antioxidant Activity of Ginseng Leaf
Molecules 2014, 19(11), 17381-17399; doi:10.3390/molecules191117381
Received: 24 August 2014 / Revised: 26 September 2014 / Accepted: 14 October 2014 / Published: 28 October 2014
Cited by 9 | PDF Full-text (1795 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to systematically evaluate the effect of the cultivation year on the quality of different ginseng tissues. Qualitative and quantitative analyses of ginsenosides were conducted using a UPLC-UV-MS method. Eight main ginsenosides in three tissues (leaf, rhizome and
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The aim of this study was to systematically evaluate the effect of the cultivation year on the quality of different ginseng tissues. Qualitative and quantitative analyses of ginsenosides were conducted using a UPLC-UV-MS method. Eight main ginsenosides in three tissues (leaf, rhizome and main root) and four parts (periderm, phloem, cambium and xylem) of ginseng aged from 1 to 13 years were determined using a UPLC-PDA method. Additionally, the antioxidant capacities of ginseng leaves were analyzed by the DPPH, ABTS and HRSA methods. It was found that the contents of ginsenosides increased with cultivation years, causing a sequential content change of ginsenosides in an organ-specific manner: leaf > rhizome > main root. The ratio between protopanaxatriol (PPT, Rg1, Re and RF) and protopanaxadiol (PPD, Rb1, Rb2, RC and Rd) in the main root remained stable (about 1.0), while it increased in leaf from 1.37 to 3.14 and decreased in the rhizome from 0.99 to 0.72. The amount of ginsenosides accumulated in the periderm was 45.48 mg/g, which was more than twice as high compared with the other three parts. Furthermore, the antioxidant activities of ginseng leaves were measured as Trolox equivalents, showing that antioxidant activity increased along with time of cultivation. The results show that the best harvest time for shizhu ginseng is the fifth year of cultivation, and the root and rhizome could be used together within seven planting years for their similar PPT/PPD level. Besides, the quality of the ginseng products would be enhanced with the periderm. The ginseng leaf is rich in ginsenosides and has potential application for its antioxidant capacity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle HPLC-UV-MS Profiles of Phenolic Compounds and Antioxidant Activity of Fruits from Three Citrus Species Consumed in Northern Chile
Molecules 2014, 19(11), 17400-17421; doi:10.3390/molecules191117400
Received: 9 August 2014 / Revised: 12 September 2014 / Accepted: 22 September 2014 / Published: 29 October 2014
Cited by 40 | PDF Full-text (2542 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Peels and edible pulp from three species of citrus including Citrus aurantifolia (varieties pica and sutil) and Citrus x lemon var. Genova widely cultivated and consumed in Northern Chile (I and II region) were analyzed for phenolic compounds and antioxidant activity for the
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Peels and edible pulp from three species of citrus including Citrus aurantifolia (varieties pica and sutil) and Citrus x lemon var. Genova widely cultivated and consumed in Northern Chile (I and II region) were analyzed for phenolic compounds and antioxidant activity for the first time. A high performance electrospray ionization mass spectrometry (HPLC-UV-ESI-MS) method was developed for the rapid identification of phenolics in extracts from peels and juices of all species. Several flavonoids including one kaempferol-O-hexoside (peak 16) and one hesperidin derivative (peak 22) three quercetin derivatives (peaks 4, 19 and 36), five isorhamnetin derivatives (peaks 5, 23, 24, 26 and 29) four luteolin derivatives (peaks 14, 25, 27 and 40), seven apigenin derivatives (peaks 2, 3, 12, 20, 34, 35 and 39), seven diosmetin derivatives (peaks 79, 17, 21, 31 and 37), three chrysoeriol derivatives (peaks 10, 18 and 30), and four eryodictiol derivatives (peaks 6, 13, 15 and 38) were identified in negative and positive mode using full scan mass measurements and MSn fragmentations. Ascorbic acid content was higher in the pulps of the varieties Genova and Sutil (60.13 ± 1.28 and 56.53 ± 1.06 mg ascorbic acid per g dry weight, respectively) while total phenolic content was higher in Pica peels followed by Sutil peels (34.59 ± 0.81 and 25.58 ± 1.02 mg/g GAE dry weight, respectively). The antioxidant capacity was also higher for Pica peels (10.34 ± 1.23 µg/mL in the DPPH assay and 120.63 ± 2.45 µM trolox equivalents/g dry weight in the FRAP assay). The antioxidant features together with the high polyphenolic contents can support at least in part, the usage of the peel extracts as nutraceutical supplements, especially to be used as anti-ageing products. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
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Open AccessArticle Field Performance Test of an Air-Cleaner with Photocatalysis-Plasma Synergistic Reactors for Practical and Long-Term Use
Molecules 2014, 19(11), 17424-17434; doi:10.3390/molecules191117424
Received: 30 August 2014 / Revised: 6 October 2014 / Accepted: 22 October 2014 / Published: 29 October 2014
Cited by 4 | PDF Full-text (618 KB) | HTML Full-text | XML Full-text
Abstract
A practical and long-term usable air-cleaner based on the synergy of photocatalysis and plasma treatments has been developed. A field test of the air-cleaner was carried out in an office smoking room. The results were compared to previously reported laboratory test results. Even
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A practical and long-term usable air-cleaner based on the synergy of photocatalysis and plasma treatments has been developed. A field test of the air-cleaner was carried out in an office smoking room. The results were compared to previously reported laboratory test results. Even after a treatment of 12,000 cigarettes-worth of tobacco smoke, the air-cleaner maintained high-level air-purification activity (98.9% ± 0.1% and 88% ± 1% removal of the total suspended particulate (TSP) and total volatile organic compound (TVOC) concentrations, respectively) at single-pass conditions. Although the removal ratio of TSP concentrations was 98.6% ± 0.2%, the ratio of TVOC concentrations was 43.8% after a treatment of 21,900 cigarettes-worth of tobacco smoke in the field test. These results indicate the importance of suitable maintenance of the reactors in the air-cleaner during field use. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessArticle Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells
Molecules 2014, 19(11), 17464-17477; doi:10.3390/molecules191117464
Received: 8 July 2014 / Revised: 27 October 2014 / Accepted: 27 October 2014 / Published: 29 October 2014
Cited by 13 | PDF Full-text (8672 KB) | HTML Full-text | XML Full-text
Abstract
Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation
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Cancer stem cells (CSCs) are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA) is a mycotoxin that induces endoplasmic reticulum (ER) stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL) compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9) activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Bowman-Birk Protease Inhibitor from Vigna unguiculata Seeds Enhances the Action of Bradykinin-Related Peptides
Molecules 2014, 19(11), 17536-17558; doi:10.3390/molecules191117536
Received: 4 September 2014 / Revised: 2 October 2014 / Accepted: 9 October 2014 / Published: 30 October 2014
Cited by 2 | PDF Full-text (2556 KB) | HTML Full-text | XML Full-text
Abstract
The hydrolysis of bradykinin (Bk) by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin
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The hydrolysis of bradykinin (Bk) by different classes of proteases in plasma and tissues leads to a decrease in its half-life. Here, Bk actions on smooth muscle and in vivo cardiovascular assays in association with a protease inhibitor, Black eyed-pea trypsin and chymotrypsin inhibitor (BTCI) and also under the effect of trypsin and chymotrypsin were evaluated. Two synthetic Bk-related peptides, Bk1 and Bk2, were used to investigate the importance of additional C-terminal amino acid residues on serine protease activity. BTCI forms complexes with Bk and analogues at pH 5.0, 7.4 and 9.0, presenting binding constants ranging from 103 to 104 M−1. Formation of BTCI-Bk complexes is probably driven by hydrophobic forces, coupled with slight conformational changes in BTCI. In vitro assays using guinea pig (Cavia porcellus) ileum showed that Bk retains the ability to induce smooth muscle contraction in the presence of BTCI. Moreover, no alteration in the inhibitory activity of BTCI in complex with Bk and analogous was observed. When the BTCI and BTCI-Bk complexes were tested in vivo, a decrease of vascular resistance and consequent hypotension and potentiating renal and aortic vasodilatation induced by Bk and Bk2 infusions was observed. These results indicate that BTCI-Bk complexes may be a reliable strategy to act as a carrier and protective approach for Bk-related peptides against plasma serine proteases cleavage, leading to an increase in their half-life. These findings also indicate that BTCI could remain stable in some tissues to inhibit chymotrypsin or trypsin-like enzymes that cleave and inactivate bradykinin in situ. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities
Molecules 2014, 19(11), 17559-17577; doi:10.3390/molecules191117559
Received: 18 August 2014 / Revised: 9 October 2014 / Accepted: 11 October 2014 / Published: 30 October 2014
Cited by 5 | PDF Full-text (398 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol) can be conjugated through terminal moieties and have therefore
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Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol) can be conjugated through terminal moieties and have therefore limited loading capacities. In this research, functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities. These poly(ethylene glycol) derivatives are conjugated to peptide sequences containing representative side-chain functionalised amino acids, using different conjugation chemistries, including copper-catalysed azide-alkyne cycloaddition, amide coupling and thiol-ene reactions. Conjugation of a sequence containing the RGD motif to poly(allyl glycidyl ether) by the thiol-ene reaction, provided a conjugate which could be used in platelet adhesion studies. Full article
(This article belongs to the Special Issue Peptide Chemistry)
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Open AccessArticle The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization
Molecules 2014, 19(11), 17578-17603; doi:10.3390/molecules191117578
Received: 26 August 2014 / Revised: 20 October 2014 / Accepted: 22 October 2014 / Published: 30 October 2014
Cited by 9 | PDF Full-text (3975 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or
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The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. Full article
(This article belongs to the Special Issue Resveratrol)
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Open AccessArticle ESI(+)-MS and GC-MS Study of the Hydrolysis of N-Azobenzyl Derivatives of Chitosan
Molecules 2014, 19(11), 17604-17618; doi:10.3390/molecules191117604
Received: 8 July 2014 / Revised: 15 October 2014 / Accepted: 23 October 2014 / Published: 30 October 2014
Cited by 1 | PDF Full-text (910 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New N-p-chloro-, N-p-bromo-, and N-p-nitrophenylazobenzylchitosan derivatives, as well as the corresponding azophenyl and azophenyl-p-sulfonic acids, were synthesized by coupling N-benzylvchitosan with aryl diazonium salts. The synthesized molecules were analyzed by UV-Vis,
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New N-p-chloro-, N-p-bromo-, and N-p-nitrophenylazobenzylchitosan derivatives, as well as the corresponding azophenyl and azophenyl-p-sulfonic acids, were synthesized by coupling N-benzylvchitosan with aryl diazonium salts. The synthesized molecules were analyzed by UV-Vis, FT-IR, 1H-NMR and 15N-NMR spectroscopy. The capacity of copper chelation by these materials was studied by AAS. Chitosan and the derivatives were subjected to hydrolysis and the products were analyzed by ESI(+)-MS and GC-MS, confirming the formation of N-benzyl chitosan. Furthermore, the MS results indicate that a nucleophilic aromatic substitution (SnAr) reaction occurs under hydrolysis conditions, yielding chloroaniline from N-p-bromo-, and N-p-nitrophenylazo-benzylchitosan as well as bromoaniline from N-p-chloro-, and N-p-nitrophenylazobenzyl-chitosan. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
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Open AccessArticle Five New Taraxerene-Type Triterpenes from the Branch Barks of Davidia involucrata
Molecules 2014, 19(11), 17619-17631; doi:10.3390/molecules191117619
Received: 8 October 2014 / Revised: 27 October 2014 / Accepted: 28 October 2014 / Published: 30 October 2014
Cited by 2 | PDF Full-text (779 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new taraxerene-type triterpenes, 2-nor-D-friedoolean-14-en-28-ol (1), 2-nor-d-friedoolean-14-en-3α,28-diol (2), 6α-hydroxy-2-nor-D-friedoolean-14-en-3,21-dione (3), 6α,11α,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (4), and 6α,23,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (5), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with five known
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Five new taraxerene-type triterpenes, 2-nor-D-friedoolean-14-en-28-ol (1), 2-nor-d-friedoolean-14-en-3α,28-diol (2), 6α-hydroxy-2-nor-D-friedoolean-14-en-3,21-dione (3), 6α,11α,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (4), and 6α,23,29-trihydroxy-D-friedoolean-14-en-3,16,21-trione (5), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with five known compounds. Their structures were elucidated by means of various spectroscopic analyses. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Changes in Phytochemical Synthesis, Chalcone Synthase Activity and Pharmaceutical Qualities of Sabah Snake Grass (Clinacanthus nutans L.) in Relation to Plant Age
Molecules 2014, 19(11), 17632-17648; doi:10.3390/molecules191117632
Received: 24 July 2014 / Revised: 7 October 2014 / Accepted: 20 October 2014 / Published: 30 October 2014
Cited by 15 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
In the current study, changes in secondary metabolite synthesis and the pharmaceutical quality of sabah snake grass leaves and buds were considered in relation to plant age (1 month, 6 months, and 1 year old). The activity of the enzyme chalcone synthase (CHS,
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In the current study, changes in secondary metabolite synthesis and the pharmaceutical quality of sabah snake grass leaves and buds were considered in relation to plant age (1 month, 6 months, and 1 year old). The activity of the enzyme chalcone synthase (CHS, EC 2.3.1.74) was measured, as it is a key enzyme for flavonoid production. Significant differences in total flavonoid (TF) production were observed between the three plant growth periods and the different plant parts. The highest contents of TF (6.32 mg/g dry weight [DW]) and total phenolic (TP) (18.21 mg/g DW) were recorded in 6-month-old buds. Among the flavonoids isolated in this study the most important ones based on concentration were from high to low as follows: catechin > quercetin > kaempferol > luteolin. Production of phenolic acids increased from 1 to 6 months, but after 6 months up to 1 year of age, they decreased significantly. The highest contents of caffeic acid (0.307 mg/g DW) and gallic acid (5.96 mg/g DW) were recorded in 1-year and 6-month-old buds, respectively. The lowest and highest activity of CHS was recorded in 1-month and 6-month-old buds with values of 3.6 and 9.5 nkat/mg protein, respectively. These results indicate that the increment in flavonoids and phenolic acids in 6-month-old buds can be attributed to an increase in CHS activity. The highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity was observed in the extract of 1-year-old buds followed by 6-month-old buds, with 50% of free radical scavenging (IC50) values of 64.6 and 73.5 µg/mL, respectively. Interestingly, a ferric reducing antioxidant power (FRAP) assay showed a higher activity in 6-month-old buds (488 μM of Fe(II)/g) than in 1-year-old buds (453 μM of Fe(II)/g), in contrast to the DPPH result. Significant correlations (p < 0.05) were observed between CHS enzyme activity and FRAP activity, TF, catechin, and kaempferol content. Extracts of 6-month-old bud exhibited a significant in vitro anticancer activity against HeLa cancer cells with IC50 value of 56.8 µg/mL. These results indicate that early harvesting of snake grass (6-month-old) may yield increased concentrations of secondary metabolites, which are potent antioxidant compounds. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle β-Sitosterol Protects against Carbon Tetrachloride Hepatotoxicity but not Gentamicin Nephrotoxicity in Rats via the Induction of Mitochondrial Glutathione Redox Cycling
Molecules 2014, 19(11), 17649-17662; doi:10.3390/molecules191117649
Received: 14 September 2014 / Revised: 23 October 2014 / Accepted: 24 October 2014 / Published: 30 October 2014
Cited by 5 | PDF Full-text (1109 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Previous findings have demonstrated that β-sitosterol (BSS), an active component of Cistanches Herba, protected against oxidant injury in H9c2 cardiomyocytes and in rat hearts by enhancing mitochondrial glutathione redox cycling, possibly through the intermediacy of mitochondrial reactive oxygen species production. We therefore hypothesized
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Previous findings have demonstrated that β-sitosterol (BSS), an active component of Cistanches Herba, protected against oxidant injury in H9c2 cardiomyocytes and in rat hearts by enhancing mitochondrial glutathione redox cycling, possibly through the intermediacy of mitochondrial reactive oxygen species production. We therefore hypothesized that BSS pretreatment can also confer tissue protection against oxidant injury in other vital organs such as liver and kidney of rats. In this study, the effects of BSS pretreatment on rat models of carbon tetrachloride (CCl4) hepatotoxicity and gentamicin nephrotoxicity were investigated. The findings showed that BSS pretreatment protected against CCl4-induced hepatotoxicity, but not gentamicin nephrotoxicity in rats. The hepatoprotection afforded by BSS was associated with the improvement in mitochondrial glutathione redox status, presumably through the glutathione reductase-mediated enhancement in mitochondrial glutathione redox cycling. The hepatoprotection afforded by BSS was also accompanied by the improved mitochondrial functional ability in rat livers. The inability of BSS to protect against gentamicin nephrotoxicity was likely due to the relatively low bioavailability of BSS in rat kidneys. BSS may serve as potential mitohormetic agent for the prevention of oxidative stress-induced injury in livers. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Flavonoids from Gynostemma pentaphyllum Exhibit Differential Induction of Cell Cycle Arrest in H460 and A549 Cancer Cells
Molecules 2014, 19(11), 17663-17681; doi:10.3390/molecules191117663
Received: 25 September 2014 / Revised: 24 October 2014 / Accepted: 24 October 2014 / Published: 31 October 2014
Cited by 14 | PDF Full-text (2797 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to
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Flavonoids, containing mainly kaempferol rhamnohexoside derivatives, were extracted from Gynostemma pentaphyllum (G. pentaphyllum) and their potential growth inhibition effects against H460 non-small cell lung cancer cells was explored and compared to that on A549 cells. The extracted flavonoids were found to exhibit antiproliferation effects against H460 cells (IC50 = 50.2 μg/mL), although the IC50 of H460 is 2.5-fold that of A549 cells (IC50 = 19.8 μg/mL). Further investigation revealed that H460 cells are more susceptible to kaempferol than A549, whereas A549 cell growth is better inhibited by kaempferol rhamnohexoside derivatives as compared with H460. In addition, flavonoids from G. pentaphyllum induced cell cycle arrest at both S and G2/M phases with concurrent modulated expression of the cellular proteins cyclin A, B, p53 and p21 in A549 cells, but not H460. On the contrary, apoptosis and concomitant alteration in balance of BCL-2 and BAX expression as well as activation of caspase-3 were equally affected between both cells by flavonoid treatment. These observations strongly suggest the growth inhibition discrepancy between H460 and A549 following flavonoid treatment can be attributed to the lack of cell cycle arrest in H460 cells and the differences between H460 and A549 cells may serve as contrasting models for further mechanistic investigations. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Optimization of Process Parameters of Extraction of Amentoflavone, Quercetin and Ginkgetin from Taxus chinensis Using Supercritical CO2 Plus Co-Solvent
Molecules 2014, 19(11), 17682-17696; doi:10.3390/molecules191117682
Received: 10 September 2014 / Revised: 28 September 2014 / Accepted: 29 September 2014 / Published: 31 October 2014
Cited by 2 | PDF Full-text (459 KB) | HTML Full-text | XML Full-text
Abstract
The effects of extraction time, temperature, pressure and different concentration of ethanol and their interactions on the yields of amentoflavone, quercetin and ginkgetin extracted from Taxus chinensis by supercritical CO2 were investigated by using a central composite design (CCD). An CCD experimental
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The effects of extraction time, temperature, pressure and different concentration of ethanol and their interactions on the yields of amentoflavone, quercetin and ginkgetin extracted from Taxus chinensis by supercritical CO2 were investigated by using a central composite design (CCD). An CCD experimental design with four factors and five levels was used to optimize the extraction parameters. Ultra performance liquid chromatography (UPLC) was used to analyze the content of the tree components in the extracts. Experimental results show that the main effects of factors and their interactions are significant on the yields (p < 0.05). The optimal extraction conditions were established for the three compounds: yield of 4.47 mg/g for amentoflavone at 48 °C, 25 MPa, 2.02 h and 78.5% ethanol, 3.73 mg/g for quercetin at 46 °C, 24 MPa, 2.3 h, 82% ethanol and 3.47 mg/g for ginkgetin at 48 °C, 20 MPa, 2.38 h, 82% ethanol, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Evaluating the Anti-Neuroinflammatory Capacity of Raw and Steamed Garlic as Well as Five Organosulfur Compounds
Molecules 2014, 19(11), 17697-17714; doi:10.3390/molecules191117697
Received: 19 September 2014 / Revised: 17 October 2014 / Accepted: 20 October 2014 / Published: 31 October 2014
Cited by 9 | PDF Full-text (935 KB) | HTML Full-text | XML Full-text
Abstract
The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS) in
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The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS) in crushed garlic. Raw garlic, but not steamed garlic, dose-dependently attenuated the production of LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and monocyte chemoattractant protein-1 (MCP-1). DATS and diallyl disulfide at 200 and 400 μM, respectively, displayed significant anti-neuroinflammatory activity. Meanwhile, even at 1 mM, diallyl sulfide, S-allyl cysteine and alliin did not display such activity. Inhibition of nuclear factor-κB activation was the mechanism underlying this protective effect of raw garlic and DATS. Analysis results indicated that the anti-neuroinflammatory capacity of raw garlic is due to the alliin-derived OSCs. Importantly, DATS is a highly promising therapeutic candidate for treating inflammation-related neurodegenerative diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Anti-Tumor Activity of Novel Aminomethylated Derivatives of Isoliquiritigenin
Molecules 2014, 19(11), 17715-17726; doi:10.3390/molecules191117715
Received: 25 August 2014 / Revised: 21 October 2014 / Accepted: 27 October 2014 / Published: 31 October 2014
Cited by 3 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new aminomethylated derivatives of isoliquiritigenin was synthesized. The structures of the compounds were confirmed by IR, MS, NMR, 13C-NMR and elemental analyses. Cytotoxic activities of these derivatives towards the human prostatic cell line PC-3, human mammary cancer cell line
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A series of new aminomethylated derivatives of isoliquiritigenin was synthesized. The structures of the compounds were confirmed by IR, MS, NMR, 13C-NMR and elemental analyses. Cytotoxic activities of these derivatives towards the human prostatic cell line PC-3, human mammary cancer cell line MCF-7 and human oophoroma cell line HO-8910 in vitro were tested. The IC50 values showed cytotoxic activities of some of these new derivatives were relatively strong. Furthermore, tumor growth inhibition in vivo of aminomethylated derivatives of isoliquiritigenin 15 was superior to that of isoliquritigenin and reached inhibition rates of 71.68%. The detailed synthesis, spectroscopic data, biological and pharmacologicalactivities of the synthesized compounds were provided. Full article
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Open AccessArticle A New Phenolic Glycoside from the Barks of Cinnamomum cassia
Molecules 2014, 19(11), 17727-17734; doi:10.3390/molecules191117727
Received: 25 September 2014 / Revised: 29 October 2014 / Accepted: 29 October 2014 / Published: 31 October 2014
Cited by 3 | PDF Full-text (273 KB) | HTML Full-text | XML Full-text
Abstract
A new phenolic glycoside (1), named methyl 2-phenylpropanoate-2-O-β-D-apiofuranosyl-(1→6)-O-β-D–glucopyranoside, was isolated from the barks of Cinnamomum cassia, along with three known phenolic glycosides and four known lignan glycosides. The structure of 1 was
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A new phenolic glycoside (1), named methyl 2-phenylpropanoate-2-O-β-D-apiofuranosyl-(1→6)-O-β-D–glucopyranoside, was isolated from the barks of Cinnamomum cassia, along with three known phenolic glycosides and four known lignan glycosides. The structure of 1 was elucidated by extensive interpretation of spectroscopic data and chemical method. Selected compounds were evaluated for their immunosuppressive activities against murine lymphocytes. Compounds 1, 2, 6 and 8 exhibited differential inhibition against ConA-induced T cells proliferation. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Hepatoprotective Effect of the Aqueous Extract of Simarouba amara Aublet (Simaroubaceae) Stem Bark against Carbon Tetrachloride (CCl4)-Induced Hepatic Damage in Rats
Molecules 2014, 19(11), 17735-17746; doi:10.3390/molecules191117735
Received: 1 September 2014 / Revised: 10 October 2014 / Accepted: 21 October 2014 / Published: 31 October 2014
Cited by 3 | PDF Full-text (748 KB) | HTML Full-text | XML Full-text
Abstract
Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on
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Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle—corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Tungsten Trioxide as a Visible Light Photocatalyst for Volatile Organic Carbon Removal
Molecules 2014, 19(11), 17747-17762; doi:10.3390/molecules191117747
Received: 27 August 2014 / Revised: 22 October 2014 / Accepted: 27 October 2014 / Published: 31 October 2014
Cited by 17 | PDF Full-text (2933 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tungsten trioxide (WO3) has been demonstrated to possess visible light photoactivity and presents a means of overcoming the UV-light dependence of photocatalysts, such as titanium dioxide. In this study, WO3 nanostructures have been synthesised by a hydrothermal method using sodium
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Tungsten trioxide (WO3) has been demonstrated to possess visible light photoactivity and presents a means of overcoming the UV-light dependence of photocatalysts, such as titanium dioxide. In this study, WO3 nanostructures have been synthesised by a hydrothermal method using sodium tungstate (Na2WO4·2H2O), sulphate precursors and pH as structure-directing agents and parameters, respectively. By altering the concentration of the sulphate precursors and pH, it was shown that different morphologies and phases of WO3 can be achieved. The effect of the morphology of the final WO3 product on the visible light photoactivity of ethylene degradation in the gas phase was investigated. In addition, platinum (Pt) was photodeposited on the WO3 structures with various morphologies to enhance the photocatalytic properties. It was found that the photocatalytic properties of the WO3 samples greatly depend on their morphology, chemical composition and surface modification. WO3 with a cuboid morphology exhibited the highest visible light photoactivity compared to other morphologies, while adding Pt to the surface improved the performance of certain WO3 structures. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessCommunication Isolation and Bioactivities of the Flavonoids Morin and Morin-3-O-β-D-glucopyranoside from Acridocarpus orientalis—A Wild Arabian Medicinal Plant
Molecules 2014, 19(11), 17763-17772; doi:10.3390/molecules191117763
Received: 10 July 2014 / Revised: 20 October 2014 / Accepted: 21 October 2014 / Published: 31 October 2014
Cited by 9 | PDF Full-text (248 KB) | HTML Full-text | XML Full-text
Abstract
Acridocarpus orientalis is an important medicinal plant for some of the locals of Arabian region. Very little is known about its phytochemical constituents. In the present study, we aimed to isolate bioactive chemicals from the crude methanolic extract of the aerial parts of
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Acridocarpus orientalis is an important medicinal plant for some of the locals of Arabian region. Very little is known about its phytochemical constituents. In the present study, we aimed to isolate bioactive chemicals from the crude methanolic extract of the aerial parts of A. orientalis. The extraction and isolation resulted in the purification of two flavonoids: morin (1) and morin-3-O-β-D-glucopyranoside (2). The structure elucidation was carried out by extensive analysis of spectroscopic data and comparison with the reported data for the known constituents. The pure isolates were subjected to various biological assays for their bioactivities. The compounds 1 and 2 were significantly active against the growth of various pathogenic fungi and phytotoxic against lettuce seed at higher concentrations. Furthermore, the free radical scavenging activities, anti-lipid peroxidation, and cytotoxic effects against HepG2, HT29, and HCT116 cancer cell lines were also assayed and the results are presented in this paper. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Antibacterial and Antioxidant Activity of Essential Oil Terpenes against Pathogenic and Spoilage-Forming Bacteria and Cell Structure-Activity Relationships Evaluated by SEM Microscopy
Molecules 2014, 19(11), 17773-17798; doi:10.3390/molecules191117773
Received: 5 August 2014 / Revised: 16 September 2014 / Accepted: 9 October 2014 / Published: 3 November 2014
Cited by 40 | PDF Full-text (4035 KB) | HTML Full-text | XML Full-text
Abstract
The antibacterial activity and antioxidant effect of the compounds α-terpineol, linalool, eucalyptol and α-pinene obtained from essential oils (EOs), against pathogenic and spoilage forming bacteria were determined. The antibacterial activities of these compounds were observed in vitro on four Gram-negative and three Gram-positive
[...] Read more.
The antibacterial activity and antioxidant effect of the compounds α-terpineol, linalool, eucalyptol and α-pinene obtained from essential oils (EOs), against pathogenic and spoilage forming bacteria were determined. The antibacterial activities of these compounds were observed in vitro on four Gram-negative and three Gram-positive strains. S. putrefaciens was the most resistant bacteria to all tested components, with MIC values of 2% or higher, whereas E. coli O157:H7 was the most sensitive strain among the tested bacteria. Eucalyptol extended the lag phase of S. Typhimurium, E. coli O157:H7 and S. aureus at the concentrations of 0.7%, 0.6% and 1%, respectively. In vitro cell growth experiments showed the tested compounds had toxic effects on all bacterial species with different level of potency. Synergistic and additive effects were observed at least one dose pair of combination against S. Typhimurium, E. coli O157:H7 and S. aureus, however antagonistic effects were not found in these combinations. The results of this first study are encouraging for further investigations on mechanisms of antimicrobial activity of these EO components. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Identification of a New Peritrophic Membrane Protein from Larval Holotrichia parallela (Coleoptera: Motschulsky)
Molecules 2014, 19(11), 17799-17809; doi:10.3390/molecules191117799
Received: 4 May 2014 / Revised: 17 July 2014 / Accepted: 17 July 2014 / Published: 3 November 2014
Cited by 3 | PDF Full-text (937 KB) | HTML Full-text | XML Full-text
Abstract
Peritrophic membranes (PMs) are composed of proteins, proteoglycans and chitin that play important roles in the structural formation and function of the PM. This study identified and characterized a new chitin binding protein named HpCBP45 by immunoscreening of the Holotrichia parallela larvae midgut
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Peritrophic membranes (PMs) are composed of proteins, proteoglycans and chitin that play important roles in the structural formation and function of the PM. This study identified and characterized a new chitin binding protein named HpCBP45 by immunoscreening of the Holotrichia parallela larvae midgut expression library. The predicted amino acid sequence indicates that it contains eight tandem chitin binding domains belonging to the peritrophin-A family. The HpCBP45 protein was expressed as a recombinant protein in the yeast Pichia pastoris and chitin binding assay demonstrated that recombinant HpCBP45 protein could strongly bind to chitin. qRT-PCR analysis showed that HpCBP45 was mainly localized in the midgut, further confirming the H. parallela PM belongs to Type I PM. The discovery and characterization of the peritrophic membrane protein HpCBP45 provides a basis for the further investigation of its biochemical and physiological functions in H. parallela. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Support for a Photoprotective Function of Winter Leaf Reddening in Nitrogen-Deficient Individuals of Lonicera japonica
Molecules 2014, 19(11), 17810-17828; doi:10.3390/molecules191117810
Received: 30 September 2014 / Revised: 28 October 2014 / Accepted: 29 October 2014 / Published: 3 November 2014
Cited by 5 | PDF Full-text (3864 KB) | HTML Full-text | XML Full-text
Abstract
Plants growing in high-light environments during winter often exhibit leaf reddening due to synthesis of anthocyanin pigments, which are thought to alleviate photooxidative stress associated with low-temperature photoinhibition through light attenuation and/or antioxidant activity. Seasonal high-light stress can be further exacerbated by a
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Plants growing in high-light environments during winter often exhibit leaf reddening due to synthesis of anthocyanin pigments, which are thought to alleviate photooxidative stress associated with low-temperature photoinhibition through light attenuation and/or antioxidant activity. Seasonal high-light stress can be further exacerbated by a limited photosynthetic capacity, such as nitrogen-deficiency. In the present study, we test the following hypotheses using three populations of the semi-evergreen vine Lonicera japonica: (1) nitrogen deficiency corresponds with reduced photosynthetic capacity; (2) individuals with reduced photosynthetic capacity synthesize anthocyanin pigments in leaves during winter; and (3) anthocyanin pigments help alleviate high-light stress by attenuating green light. All populations featured co-occurring winter-green and winter-red leafed individuals on fully-exposed (high-light), south-facing slopes in the Piedmont of North Carolina, USA. Consistent with our hypotheses, red leaves consistently exhibited significantly lower foliar nitrogen than green leaves, as well as lower total chlorophyll, quantum yield efficiency, carboxylation efficiency, and photosynthesis at saturating irradiance (Asat). Light-response curves measured using ambient sunlight versus red-blue LED (i.e., lacking green wavelengths) demonstrated significantly reduced quantum yield efficiency and a higher light compensation point under sunlight relative to red-blue LED in red leaves, but not in green leaves, consistent with a (green) light-attenuating function of anthocyanin pigments. These results are consistent with the hypothesis that intraspecific anthocyanin synthesis corresponds with nitrogen deficiency and reduced photosynthetic capacity within populations, and support a light-attenuating function of anthocyanin pigments. Full article
(This article belongs to the Special Issue Anthocyanins) Printed Edition available
Open AccessArticle Antioxidant and Anticancer Aporphine Alkaloids from the Leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena
Molecules 2014, 19(11), 17829-17838; doi:10.3390/molecules191117829
Received: 2 September 2014 / Revised: 28 October 2014 / Accepted: 31 October 2014 / Published: 3 November 2014
Cited by 18 | PDF Full-text (267 KB) | HTML Full-text | XML Full-text
Abstract
Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2), (−)-anonaine (3), (−)-asimilobine (4), (−)-caaverine (5), (−)-N-methylasimilobine (
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Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2), (−)-anonaine (3), (−)-asimilobine (4), (−)-caaverine (5), (−)-N-methylasimilobine (6), (−)-nuciferine (7), (−)-nornuciferine (8), (−)-roemerine (9), 7-hydroxydehydronuciferine (10) cepharadione B (11), β-sitostenone (12), stigmasta-4,22-dien-3-one (13) and two chlorophylls: pheophytin-a (14) and aristophyll-C (15). The anti-oxidation activity of the compounds was examined by antiradical scavenging, metal chelating and ferric reducing power assays. The results have shown that these compounds have antioxidative activity. The study has also examined the antiproliferation activity of the isolated compounds against human melanoma, prostate and gastric cancer cells. The results shown that 7-hydroxydehydronuciferine (10) significantly inhibited the proliferation of melanoma, prostate and gastric cancer cells. Together, these findings suggest that leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena are a good resource for obtaining the biologically active substances with antioxidant properties. Full article
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
Open AccessArticle A New Prenylated Indole Diketopiperazine Alkaloid from Eurotium cristatum
Molecules 2014, 19(11), 17839-17847; doi:10.3390/molecules191117839
Received: 11 September 2014 / Revised: 27 October 2014 / Accepted: 29 October 2014 / Published: 3 November 2014
Cited by 9 | PDF Full-text (291 KB) | HTML Full-text | XML Full-text
Abstract
A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus
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A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus Eurotium cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The absolute configuration of 1 was assigned using Marfey’s method applied to its acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre-adipocytes. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Preparation of Risedronate Nanoparticles by Solvent Evaporation Technique
Molecules 2014, 19(11), 17848-17861; doi:10.3390/molecules191117848
Received: 29 August 2014 / Revised: 23 October 2014 / Accepted: 24 October 2014 / Published: 4 November 2014
Cited by 11 | PDF Full-text (7403 KB) | HTML Full-text | XML Full-text
Abstract
One approach for the enhancement of oral drug bioavailability is the technique of nanoparticle preparation. Risedronate sodium (Biopharmaceutical Classification System Class III) was chosen as a model compound with high water solubility and low intestinal permeability. Eighteen samples of risedronate sodium were prepared
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One approach for the enhancement of oral drug bioavailability is the technique of nanoparticle preparation. Risedronate sodium (Biopharmaceutical Classification System Class III) was chosen as a model compound with high water solubility and low intestinal permeability. Eighteen samples of risedronate sodium were prepared by the solvent evaporation technique with sodium dodecyl sulfate, polysorbate, macrogol, sodium carboxymethyl cellulose and sodium carboxymethyl dextran as nanoparticle stabilizers applied in three concentrations. The prepared samples were characterized by dynamic light scattering and scanning electron microscopy. Fourier transform mid-infrared spectroscopy was used for verification of the composition of the samples. The particle size of sixteen samples was less than 200 nm. Polysorbate, sodium carboxymethyl dextran and macrogol were determined as the most favourable excipients; the particle size of the samples of risedronate with these excipients ranged from 2.8 to 10.5 nm. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Chemical Constituents of Kino Extract from Corymbia torelliana
Molecules 2014, 19(11), 17862-17871; doi:10.3390/molecules191117862
Received: 27 August 2014 / Revised: 27 October 2014 / Accepted: 28 October 2014 / Published: 4 November 2014
Cited by 7 | PDF Full-text (359 KB) | HTML Full-text | XML Full-text
Abstract
Seven flavanones were identified from kino exudate of Corymbia torelliana by spectroscopic and spectrometric methods including UV, 1D and 2D NMR and UPLC-HR-MS. The study identified seven molecules, namely 3,4',5,7-tetrahydroxyflavanone (1), 3',4',5,7-tetrahydroxyflavanone (2), 4',5,7-trihydroxyflavanone (3), 3,4',5-trihydroxy-7-methoxyflavanone (
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Seven flavanones were identified from kino exudate of Corymbia torelliana by spectroscopic and spectrometric methods including UV, 1D and 2D NMR and UPLC-HR-MS. The study identified seven molecules, namely 3,4',5,7-tetrahydroxyflavanone (1), 3',4',5,7-tetrahydroxyflavanone (2), 4',5,7-trihydroxyflavanone (3), 3,4',5-trihydroxy-7-methoxyflavanone (4), (+)-(2S)-4',5,7-trihydroxy-6-methylflavanone (5), 4',5,7-trihydroxy-6,8-dimethylflavanone (6) and 4',5-dihydroxy-7-methoxyflavanone (7) from this eucalypt species. This is the first report of these natural products from C. torelliana kino exudate. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle RNA/aTNA Chimeras: RNAi Effects and Nucleases Resistance of Single and Double Stranded RNAs
Molecules 2014, 19(11), 17872-17896; doi:10.3390/molecules191117872
Received: 18 August 2014 / Revised: 14 October 2014 / Accepted: 15 October 2014 / Published: 4 November 2014
Cited by 5 | PDF Full-text (1550 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The RNA interference pathway (RNAi) is a specific and powerful biological process, triggered by small non-coding RNA molecules and involved in gene expression regulation. In this work, we explored the possibility of increasing the biological stability of these RNA molecules by replacing their
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The RNA interference pathway (RNAi) is a specific and powerful biological process, triggered by small non-coding RNA molecules and involved in gene expression regulation. In this work, we explored the possibility of increasing the biological stability of these RNA molecules by replacing their natural ribose ring with an acyclic L-threoninol backbone. In particular, this modification has been incorporated at certain positions of the oligonucleotide strands and its effects on the biological properties of the siRNA have been evaluated. In vitro cellular RNAi assays have demonstrated that the L-threoninol backbone is well tolerated by the RNAi machinery in both double and single-stranded fashion, with activities significantly higher than those evinced by the unmodified RNAs and comparable to the well-known phosphorothioate modification. Additionally, this modification conferred extremely strong resistance to serum and 3′/5′-exonucleases. In view of these results, we applied this modification to the knockdown of a therapeutically relevant human gene such as apolipoprotein B (ApoB). Further studies on the activation of the innate immune system showed that L-threoninol-modified RNAs are slightly less stimulatory than unmodified RNAs. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Antifungal Activity and Computational Study of Constituents from Piper divaricatum Essential Oil against Fusarium Infection in Black Pepper
Molecules 2014, 19(11), 17926-17942; doi:10.3390/molecules191117926
Received: 25 August 2014 / Revised: 12 October 2014 / Accepted: 23 October 2014 / Published: 4 November 2014
Cited by 8 | PDF Full-text (2464 KB) | HTML Full-text | XML Full-text
Abstract
Fusarium disease causes considerable losses in the cultivation of Piper nigrum, the black pepper used in the culinary world. Brazil was the largest producer of black pepper, but in recent years has lost this hegemony, with a significant reduction in its production,
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Fusarium disease causes considerable losses in the cultivation of Piper nigrum, the black pepper used in the culinary world. Brazil was the largest producer of black pepper, but in recent years has lost this hegemony, with a significant reduction in its production, due to the ravages produced by the Fusarium solani f. sp. piperis, the fungus which causes this disease. Scientific research seeks new alternatives for the control and the existence of other Piper species in the Brazilian Amazon, resistant to disease, are being considered in this context. The main constituents of the oil of Piper divaricatum are methyleugenol (75.0%) and eugenol (10.0%). The oil and these two main constituents were tested individually at concentrations of 0.25 to 2.5 mg/mL against F. solani f. sp. piperis, exhibiting strong antifungal index, from 18.0% to 100.0%. The 3D structure of the β-glucosidase from Fusarium solani f. sp. piperis, obtained by homology modeling, was used for molecular docking and molecular electrostatic potential calculations in order to determine the binding energy of the natural substrates glucose, methyleugenol and eugenol. The results showed that β-glucosidase (Asp45, Arg113, Lys146, Tyr193, Asp225, Trp226 and Leu99) residues play an important role in the interactions that occur between the protein-substrate and the engenol and methyleugenol inhibitors, justifying the antifungal action of these two phenylpropenes against Fusarium solani f. sp. piperis. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Efficiency of Vanilla, Patchouli and Ylang Ylang Essential Oils Stabilized by Iron Oxide@C14 Nanostructures against Bacterial Adherence and Biofilms Formed by Staphylococcus aureus and Klebsiella pneumoniae Clinical Strains
Molecules 2014, 19(11), 17943-17956; doi:10.3390/molecules191117943
Received: 9 September 2014 / Revised: 22 October 2014 / Accepted: 29 October 2014 / Published: 4 November 2014
Cited by 10 | PDF Full-text (9177 KB) | HTML Full-text | XML Full-text
Abstract
Biofilms formed by bacterial cells are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence and chronicization of the microbial infections and to therapy failure. The purpose of this study was to combine the unique properties of magnetic nanoparticles
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Biofilms formed by bacterial cells are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence and chronicization of the microbial infections and to therapy failure. The purpose of this study was to combine the unique properties of magnetic nanoparticles with the antimicrobial activity of three essential oils to obtain novel nanobiosystems that could be used as coatings for catheter pieces with an improved resistance to Staphylococcus aureus and Klebsiella pneumoniae clinical strains adherence and biofilm development. The essential oils of ylang ylang, patchouli and vanilla were stabilized by the interaction with iron oxide@C14 nanoparticles to be further used as coating agents for medical surfaces. Iron oxide@C14 was prepared by co-precipitation of Fe+2 and Fe+3 and myristic acid (C14) in basic medium. Vanilla essential oil loaded nanoparticles pelliculised on the catheter samples surface strongly inhibited both the initial adherence of S. aureus cells (quantified at 24 h) and the development of the mature biofilm quantified at 48 h. Patchouli and ylang-ylang essential oils inhibited mostly the initial adherence phase of S. aureus biofilm development. In the case of K. pneumoniae, all tested nanosystems exhibited similar efficiency, being active mostly against the adherence K. pneumoniae cells to the tested catheter specimens. The new nanobiosystems based on vanilla, patchouli and ylang-ylang essential oils could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with anti-adherence and anti-biofilm properties. Full article
(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)
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Open AccessArticle A Novel Method HPLC-DAD Analysis of the Contentsof Moutan Cortexand Paeoniae Radix Alba with Similar Constituents-Monoterpene Glycosides in Guizhi Fuling Wan
Molecules 2014, 19(11), 17957-17967; doi:10.3390/molecules191117957
Received: 9 September 2014 / Revised: 23 October 2014 / Accepted: 29 October 2014 / Published: 4 November 2014
Cited by 4 | PDF Full-text (426 KB) | HTML Full-text | XML Full-text
Abstract
A variety of traditional Chinese medical formulations contain two or more herbs from the same genus or family. Although these herbs may have a similar appearance and constituents, they usually have different pharmacodynamic actions. A series of qualitative and quantitative analysis methods are
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A variety of traditional Chinese medical formulations contain two or more herbs from the same genus or family. Although these herbs may have a similar appearance and constituents, they usually have different pharmacodynamic actions. A series of qualitative and quantitative analysis methods are developed to determine one or more compounds for quality control of medicine. As far as we know, no method has been found to determine the real ratio of the two herbs along with the prescription. In this study, we used HPLC-DAD as a way to determine the content of Moutan cortex (M) and Paeoniae radix alba (P) in GuizhiFuling Wan (GZFLW). An effective, accurate and reliable HPLC-DAD method was developed for detecting the content of M and P in GZFLW through the analysis of four monoterpeneglycosides, namely, galloylpaeoniflorin (1), paeoniflorin (2), mudanpioside C (3) and benzoylpaeoniflorin (4). Due to the different UV characteristics of the compounds, the detection wavelength was 270 nm for 1 and 2, while 3 and 4 were monitored at 254 nm and 230 nm, respectively. Four equations were put forward to describe the relationship between content of M as well as P and the four monoterpene glycosides in GZFLW. After validation, all the accuracies of the M and P contents in GZFLW were within 10%. The result showed that the method could be successfully applied to analyze the contents of M and P in GZFLW. Moreover, our method may be more widely used to control the quality of proprietary Chinese medicines, especially for those containing the same genus or family herbs, in industrial GMP production. Full article
Open AccessArticle Rational Design and Synthesis of Altered Peptide Ligands based on Human Myelin Oligodendrocyte Glycoprotein 35–55 Epitope: Inhibition of Chronic Experimental Autoimmune Encephalomyelitis in Mice
Molecules 2014, 19(11), 17968-17984; doi:10.3390/molecules191117968
Received: 25 July 2014 / Revised: 24 October 2014 / Accepted: 27 October 2014 / Published: 4 November 2014
Cited by 6 | PDF Full-text (580 KB) | HTML Full-text | XML Full-text
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the
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Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35–55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR) contact residues of the human MOG35–55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35–55 peptide at the time of immunization. Full article
(This article belongs to the Special Issue Peptide Chemistry)
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Open AccessArticle Effects of Tetraethyl Orthosilicate (TEOS) on the Light and Temperature Stability of a Pigment from Beta vulgaris and Its Potential Food Industry Applications
Molecules 2014, 19(11), 17985-18002; doi:10.3390/molecules191117985
Received: 5 September 2014 / Revised: 20 October 2014 / Accepted: 29 October 2014 / Published: 5 November 2014
Cited by 7 | PDF Full-text (1123 KB) | HTML Full-text | XML Full-text
Abstract
A novel, simple and inexpensive modification method using TEOS to increase the UV light, pH and temperature stability of a red-beet-pigment extracted from Beta vulgaris has been proposed. The effects on the molecular structure of betalains were studied by FTIR spectroscopy. The presence
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A novel, simple and inexpensive modification method using TEOS to increase the UV light, pH and temperature stability of a red-beet-pigment extracted from Beta vulgaris has been proposed. The effects on the molecular structure of betalains were studied by FTIR spectroscopy. The presence of betacyanin was verified by UV-Vis spectroscopy and its degradation in modified red-beet-pigment was evaluated and compared to the unmodified red-beet-pigment; performance improvements of 88.33%, 16.84% and 20.90% for UV light, pH and temperature stability were obtained, respectively,. Measurements of reducing sugars, phenol, and antioxidant contents were performed on unmodified and modified red-beet-pigment and losses of close to 21%, 54% and 36%, respectively, were found to be caused by the addition of TEOS. Polar diagrams of color by unmodified and modified red-beet-pigment in models of a beverage and of a yogurt were obtained and the color is preserved, although here is a small loss in the chromaticity parameter of the modified red-beet-pigment. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Exogenous Spermidine Improves Seed Germination of White Clover under Water Stress via Involvement in Starch Metabolism, Antioxidant Defenses and Relevant Gene Expression
Molecules 2014, 19(11), 18003-18024; doi:10.3390/molecules191118003
Received: 19 September 2014 / Revised: 27 October 2014 / Accepted: 27 October 2014 / Published: 5 November 2014
Cited by 14 | PDF Full-text (693 KB) | HTML Full-text | XML Full-text
Abstract
This study was designed to determine the effect of exogenous spermidine (Spd) (30 μM) on white clover seed germination under water stress induced by polyethylene glycol 6000. Use of seed priming with Spd improved seed germination percentage, germination vigor, germination index, root viability
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This study was designed to determine the effect of exogenous spermidine (Spd) (30 μM) on white clover seed germination under water stress induced by polyethylene glycol 6000. Use of seed priming with Spd improved seed germination percentage, germination vigor, germination index, root viability and length, and shortened mean germination time under different water stress conditions. Seedling fresh weight and dry weight also increased significantly in Spd-treated seeds compared with control (seeds primed with distilled water). Improved starch metabolism was considered a possible reason for this seed invigoration, since seeds primed with Spd had significantly increased α-amylase/β-amylase activities, reducing sugar, fructose and glucose content and transcript level of β-amylase gene but not transcript level of α-amylase gene. In addition, the physiological effects of exogenous Spd on improving seeds’ tolerance to water deficit during germination were reflected by lower lipid peroxidation levels, better cell membrane stability and significant higher seed vigour index in seedlings. Enhanced antioxidant enzyme activities (superoxide dismutase, peroxidase, catalase and ascorbate peroxidase), ascorbate-glutathione cycle (ASC-GSH cycle) and transcript level of genes encoding antioxidant enzymes induced by exogenous Spd may be one of the critical reasons behind acquired drought tolerance through scavenging of reactive oxygen species (ROS) in water-stressed white clover seeds. The results indicate that Spd plays an important function as a stress-protective compound or physiological activator. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Dysidinoid A, an Unusual Meroterpenoid with Anti-MRSA Activity from the South China Sea Sponge Dysidea sp.
Molecules 2014, 19(11), 18025-18032; doi:10.3390/molecules191118025
Received: 19 October 2014 / Revised: 30 October 2014 / Accepted: 30 October 2014 / Published: 5 November 2014
Cited by 8 | PDF Full-text (292 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid
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An unusual meroterpenoid, dysidinoid A (1), was isolated from the South China Sea sponge Dysidea sp. Its structure was elucidated by extensive spectroscopic methods including HRESIMS and 2D NMR, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Dysidinoid A (1) is the first meroterpenoid from Nature bearing a 9,4-friedodrime skeleton and a 2,5-dionepyrrole unit. Dysidinoid A (1) showed potent antibacterial activity against two strains of pathogenic bacteria methicillin-resistant Staphylococcus aureus (MRSA) with MIC90 values of 8.0 μg/mL against both. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis and Biological Evaluation of Liguzinediol Mono- and Dual Ester Prodrugs as Promising Inotropic Agents
Molecules 2014, 19(11), 18057-18072; doi:10.3390/molecules191118057
Received: 2 September 2014 / Revised: 29 October 2014 / Accepted: 29 October 2014 / Published: 5 November 2014
Cited by 6 | PDF Full-text (302 KB) | HTML Full-text | XML Full-text
Abstract
The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain
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The potent positive inotropic effect, together with the relatively low safety risk of liguzinediol (LZDO), relative to currently available inotropic drugs, has prompted us to intensively research and develop LZDO as a potent positive inotropic agent. In this study, to obtain LZDO alternatives for oral chronic administration, a series of long-chain fatty carboxylic mono- and dual-esters of LZDO were synthesized, and preliminarily evaluated for physicochemical properties and bioconversion. Enhanced lipophilic properties and decreased solubility of the prodrugs were observed as the side chain length increased. All esters showed conspicuous chemical stability in phosphate buffer (pH 7.4). Moreover, the enzymatic hydrolysis of esters in human plasma and human liver microsomes confirmed that the majority of esters were converted to LZDO, with release profiles that varied due to the size and structure of the side chain. In vivo pharmacokinetic studies following oral administration of monopivaloyl (M5), monodecyl (M10) and monododecyl (M12) esters demonstrated the evidently extended half-lives relative to LZDO dosed alone. In particular the monopivaloyl ester M5 exhibited an optimal pharmacokinetic profile with appropriate physiochemical characteristics. Full article
(This article belongs to the Special Issue Prodrugs)
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Open AccessArticle Anti-Inflammatory Effect of Methylpenicinoline from a Marine Isolate of Penicillium sp. (SF-5995): Inhibition of NF-κB and MAPK Pathways in Lipopolysaccharide-Induced RAW264.7 Macrophages and BV2 Microglia
Molecules 2014, 19(11), 18073-18089; doi:10.3390/molecules191118073
Received: 25 September 2014 / Revised: 28 October 2014 / Accepted: 28 October 2014 / Published: 5 November 2014
Cited by 13 | PDF Full-text (1038 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS)
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In the course of a search for anti-inflammatory metabolites from marine-derived fungi, methylpenicinoline (1) was isolated from a marine isolate of Penicillin sp. Compound 1 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production by suppressing the expression of inducible NO synthase (iNOS) in RAW264.7 macrophages and BV2 microglia. It also attenuated prostaglandin E2 (PGE2) production by suppressing cyclooxygenase-2 (COX-2) expression in a concentration-dependent manner (from 10 μM to 80 μM) without affecting cell viability. In addition, compound 1 reduced the production of the pro-inflammatory cytokine interleukin-1β (IL-1β). In a further study designed to elucidate the mechanism of its anti-inflammatory effects, compound 1 was shown to block nuclear factor-kappa B (NF-κB) activation in LPS-induced RAW264.7 macrophages and BV2 microglia by inhibiting the phosphorylation of inhibitor kappa B-α (IκB-α), thereby suppressing the nuclear translocation of NF-κB dimers, namely p50 and p65, that are known to be crucial molecules associated with iNOS and COX-2 expression. In addition, compound 1 inhibited the activation of mitogen-activated protein kinase (MAPK) pathways. Taken together, the results suggest that compound 1 might be a valuable therapeutic agent for the treatment of anti-inflammatory and anti-neuroinflammatory diseases. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Analysis on the Interaction Domain of VirG and Apyrase by Pull-Down Assay
Molecules 2014, 19(11), 18090-18101; doi:10.3390/molecules191118090
Received: 10 September 2014 / Revised: 19 October 2014 / Accepted: 21 October 2014 / Published: 5 November 2014
Cited by 2 | PDF Full-text (2251 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
VirG is outer membrane protein of Shigella and affects the spread of Shigella. Recently it has been reported that apyrase influences the location of VirG, although the underlying mechanism remains poorly understood. The site of interaction between apyrase and VirG is the
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VirG is outer membrane protein of Shigella and affects the spread of Shigella. Recently it has been reported that apyrase influences the location of VirG, although the underlying mechanism remains poorly understood. The site of interaction between apyrase and VirG is the focus of our research. First we constructed recombinant plasmid pHIS-phoN2 and pS-(v1–1102, v53–758, v759–1102, v53–319, v320–507, v507–758) by denaturation-renaturation, the phoN2:kan mutant of Shigella flexneri 5a M90T by a modified version of the lambda red recombination protocol originally described by Datsenko and Wanner and the complemented strain M90TΔphoN2/pET24a(PhisphoN2). Second, the recombinant plasmid pHIS-phoN2 and the pS-(v1–1102, v53–758, v759–1102, v53–319, v320–507, v507–758) were transformed into E. coli BL21 (DE3) and induced to express the fusion proteins. Third, the fusion proteins were purified and the interaction of VirG and apyrase was identified by pull-down. Fourth, VirG was divided and the interaction site of apyrase and VirG was determined. Finally, how apyrase affects the function of VirG was analyzed by immunofluorescence. Accordingly, the results provided the data supporting the fact that apyrase combines with the α-domain of VirG to influence the function of VirG. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Absorbability, Mechanism and Structure-Property Relationship of Three Phenolic Acids from the Flowers of Trollius chinensis
Molecules 2014, 19(11), 18129-18138; doi:10.3390/molecules191118129
Received: 18 July 2014 / Revised: 1 October 2014 / Accepted: 27 October 2014 / Published: 5 November 2014
Cited by 1 | PDF Full-text (899 KB) | HTML Full-text | XML Full-text
Abstract
The absorption properties, mechanism of action, and structure-property relationship of three phenolic acids isolated from the flowers of Trollius chinensis Bunge, namely, proglobeflowery acid (PA), globeflowery acid (GA) and trolloside (TS), were investigated using the human Caco-2 cell monolayer model. The results
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The absorption properties, mechanism of action, and structure-property relationship of three phenolic acids isolated from the flowers of Trollius chinensis Bunge, namely, proglobeflowery acid (PA), globeflowery acid (GA) and trolloside (TS), were investigated using the human Caco-2 cell monolayer model. The results showed that these three phenolic acids were transported across the Caco-2 cell monolayer in a time and concentration dependent manner at the Papp level of 10−5 cm/s, and their extent of absorption correlated with their polarity and molecular weight. In conclusion, all three of these compounds were easily absorbed through passive diffusion, which implied their high bioavailability and significant contribution to the effectiveness of T. chinensis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antimicrobial Activity of UV-Induced Phenylamides from Rice Leaves
Molecules 2014, 19(11), 18139-18151; doi:10.3390/molecules191118139
Received: 20 October 2014 / Revised: 3 November 2014 / Accepted: 4 November 2014 / Published: 6 November 2014
Cited by 10 | PDF Full-text (1084 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Rice produces a wide array of phytoalexins in response to pathogen attacks and UV-irradiation. Except for the flavonoid sakuranetin, most phytoalexins identified in rice are diterpenoid compounds. Analysis of phenolic-enriched fractions from UV-treated rice leaves showed that several phenolic compounds in addition to
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Rice produces a wide array of phytoalexins in response to pathogen attacks and UV-irradiation. Except for the flavonoid sakuranetin, most phytoalexins identified in rice are diterpenoid compounds. Analysis of phenolic-enriched fractions from UV-treated rice leaves showed that several phenolic compounds in addition to sakuranetin accumulated remarkably in rice leaves. We isolated two compounds from UV-treated rice leaves using silica gel column chromatography and preparative HPLC. The isolated phenolic compounds were identified as phenylamide compounds: N-trans-cinnamoyltryptamine and N-p-coumaroylserotonin. Expression analysis of biosynthetic genes demonstrated that genes for arylamine biosynthesis were upregulated by UV irradiation. This result suggested that phenylamide biosynthetic pathways are activated in rice leaves by UV treatment. To unravel the role of UV-induced phenylamides as phytoalexins, we examined their antimicrobial activity against rice fungal and bacterial pathogens. N-trans-Cinnamoyltryptamine inhibited the growth of rice brown spot fungus (Bipolaris oryzae). In addition to the known antifungal activity to the blast fungus, sakuranetin had antimicrobial activity toward B. oryzae and Rhizoctonia solani (rice sheath blight fungus). UV-induced phenylamides and sakuranetin also had antimicrobial activity against rice bacterial pathogens for grain rot (Burkholderia glumae), blight (Xanthomonas oryzae pv. oryzae) and leaf streak (X. oryzae pv. oryzicola) diseases. These findings suggested that the UV-induced phenylamides in rice are phytoalexins against a diverse array of pathogens. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Novel Flavonol Glycosides from the Aerial Parts of Lentil (Lens culinaris)
Molecules 2014, 19(11), 18152-18178; doi:10.3390/molecules191118152
Received: 18 September 2014 / Revised: 30 October 2014 / Accepted: 31 October 2014 / Published: 6 November 2014
Cited by 5 | PDF Full-text (1053 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
While the phytochemical composition of lentil (Lens culinaris) seeds is well described in scientific literature, there is very little available data about secondary metabolites from lentil leaves and stems. Our research reveals that the aerial parts of lentil are a rich
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While the phytochemical composition of lentil (Lens culinaris) seeds is well described in scientific literature, there is very little available data about secondary metabolites from lentil leaves and stems. Our research reveals that the aerial parts of lentil are a rich source of flavonoids. Six kaempferol and twelve quercetin glycosides were isolated, their structures were elucidated using NMR spectroscopy and chemical methods. This group includes 16 compounds which have not been previously described in the scientific literature: quercetin 3-O-β-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (1), kaempferol 3-O-β-D-glucopyranosyl(1→2)-β-D-galacto-pyranoside-7-O-β-D-glucuropyranoside (3), their derivatives 410,1215,17,18 acylated with caffeic, p-coumaric, ferulic, or 3,4,5-trihydroxycinnamic acid and kaempferol 3-O-{[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl(1→2)]-α-L-rhamnopyranosyl(1→6)}-β-D-galactopyranoside-7-O-α-L-rhamnopyranoside (11). Their DPPH scavenging activity was also evaluated. This is probably the first detailed description of flavonoids from the aerial parts of lentil. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Icariin Is A PPARα Activator Inducing Lipid Metabolic Gene Expression in Mice
Molecules 2014, 19(11), 18179-18191; doi:10.3390/molecules191118179
Received: 5 September 2014 / Revised: 12 October 2014 / Accepted: 13 October 2014 / Published: 6 November 2014
Cited by 6 | PDF Full-text (770 KB) | HTML Full-text | XML Full-text
Abstract
Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg,
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Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg) for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA) binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2) were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh) were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1) and FA synthetase (Fasn) were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents
Molecules 2014, 19(11), 18215-18231; doi:10.3390/molecules191118215
Received: 25 August 2014 / Revised: 27 October 2014 / Accepted: 28 October 2014 / Published: 7 November 2014
Cited by 14 | PDF Full-text (2611 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays.
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A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3β-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3β-L-lysine ester-6g not only displayed good cytotoxicity (IC50 < 3.5 μM) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50 = 4.884 μM) had lower nephrotoxicity than both 6g (IC50 = 2.310 μM) and cisplatin (CDDP, IC50 = 3.691 μM) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Sulfated Chitosan Oligosaccharides Suppress LPS-Induced NO Production via JNK and NF-κB Inactivation
Molecules 2014, 19(11), 18232-18247; doi:10.3390/molecules191118232
Received: 5 August 2014 / Revised: 12 September 2014 / Accepted: 4 November 2014 / Published: 7 November 2014
Cited by 14 | PDF Full-text (1359 KB) | HTML Full-text | XML Full-text
Abstract
Various biological effects have been reported for sulfated chitosan oligosaccharides, but the molecular mechanisms of action of their anti-inflammatory effects are still unknown. This study aimed to evaluate the anti-inflammatory effects of sulfated chitosan oligosaccharides and to elucidate the possible mechanisms of action.
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Various biological effects have been reported for sulfated chitosan oligosaccharides, but the molecular mechanisms of action of their anti-inflammatory effects are still unknown. This study aimed to evaluate the anti-inflammatory effects of sulfated chitosan oligosaccharides and to elucidate the possible mechanisms of action. The results showed that pretreated low molecular weight sulfated chitosan oligosaccharides inhibited the production of nitric oxide (NO) and inflammatory cytokines such as IL-6 and TNF-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. The sulfated chitosan oligosaccharides also suppressed inducible nitric oxide synthase (iNOS), phosphorylation of JNK and translocation of p65, a subunit of NF-κB, into the nucleus by inhibiting degradation of IκB-α. Our investigation suggests sulfated chitosan oligosaccharides inhibit IL-6/TNF-α in LPS-induced macrophages, regulated by mitogen-activated protein kinases (MAPKs) pathways dependent on NF-κB activation. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
Open AccessArticle Efficacy Evaluation of a Multifunctional Cosmetic Formulation: The Benefits of a Combination of Active Antioxidant Substances
Molecules 2014, 19(11), 18268-18282; doi:10.3390/molecules191118268
Received: 29 April 2014 / Revised: 30 September 2014 / Accepted: 30 September 2014 / Published: 10 November 2014
Cited by 9 | PDF Full-text (463 KB) | HTML Full-text | XML Full-text
Abstract
This study presents the association of active antioxidants substances in a multifunctional cosmetic formulation with established efficacy against signs of aging. A multifunctional cosmetic formulation containing an association of UV filters and antioxidant substances (liposoluble vitamins A, C and E, Ginkgo biloba and
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This study presents the association of active antioxidants substances in a multifunctional cosmetic formulation with established efficacy against signs of aging. A multifunctional cosmetic formulation containing an association of UV filters and antioxidant substances (liposoluble vitamins A, C and E, Ginkgo biloba and Phorphyra umbilicalis extracts) was evaluated. This formulation was submitted to a clinical efficacy study using biophysics techniques and skin images analysis (digital photography imaging systems, 20 MHz ultrasound, and reflectance confocal microscopy). The volunteers applied the formulation containing the UV filters and antioxidant substances during the day and the formulation with antioxidant substances and without the UV filters at night, for 90 days. The formulation increased the hydration and protected the skin barrier function after a single application. At the long term assessment the formulation provided an improvement in skin barrier function and skin hydration to the deeper layers of the epidermis, leading to an improvement in skin appearance by reducing wrinkles and skin roughness. The multifunctional cosmetic formulation studied can be suggested to preventing signs of aging and improving skin conditions. In addition, this study presents the benefits of associating different active antioxidants substances in a single cosmetic formulation to prevent skin aging. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Curcumin Reverse Methicillin Resistance in Staphylococcus aureus
Molecules 2014, 19(11), 18283-18295; doi:10.3390/molecules191118283
Received: 5 September 2014 / Revised: 25 September 2014 / Accepted: 11 October 2014 / Published: 10 November 2014
Cited by 16 | PDF Full-text (1440 KB) | HTML Full-text | XML Full-text
Abstract
Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to
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Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., was shown to possess superior potency to resensitize methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics. Previous studies have shown the synergistic activity of curcumin with β-lactam and quinolone antibiotics. Further, to understand the anti-MRSA mechanism of curcumin, we investigated the potentiated effect of curcumin by its interaction in diverse conditions. The mechanism of anti-MRSA action of curcumin was analyzed by the viability assay in the presence of detergents, ATPase inhibitors and peptidoglycan (PGN) from S. aureus, and the PBP2a protein level was analyzed by western blotting. The morphological changes in the curcumin-treated MRSA strains were investigated by transmission electron microscopy (TEM). We analyzed increased susceptibility to MRSA isolates in the presence of curcumin. The optical densities at 600 nm (OD600) of the suspensions treated with the combinations of curcumin with triton X-100 and Tris were reduced to 63% and 59%, respectively, compared to curcumin without treatment. N,N'-dicyclohexylcarbodiimide (DCCD) and sodium azide (NaN3) were reduced to 94% and 55%, respectively. When peptidoglycan (PGN) from S. aureus was combined with curcumin, PGN (0–125 μg/mL) gradually blocked the antibacterial activity of curcumin (125 μg/mL); however, at a concentration of 125 µg/mL PGN, it did not completely block curcumin. Curcumin has a significant effect on the protein level of PBP2a. The TEM images of MRSA showed damage of the cell wall, disruption of the cytoplasmic contents, broken cell membrane and cell lysis after the treatment of curcumin. These data indicate a remarkable antibacterial effect of curcumin, with membrane permeability enhancers and ATPase inhibitors, and curcumin did not directly bind to PGN on the cell wall. Further, the antimicrobial action of curcumin involved in the PBP2a-mediated resistance mechanism was investigated. Full article
(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)
Open AccessArticle A Novel HPLC-Assisted Method for Investigation of the Fe2+-Chelating Activity of Flavonoids and Plant Extracts
Molecules 2014, 19(11), 18296-18316; doi:10.3390/molecules191118296
Received: 15 October 2014 / Revised: 5 November 2014 / Accepted: 6 November 2014 / Published: 10 November 2014
Cited by 11 | PDF Full-text (978 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoids are a class of natural phenolic compounds that show antioxidant properties. Besides the known mechanisms of action of flavonoids (binding/inactivation of free radicals and other reactive oxygen species) that determine this effect, an important factor is their ability to bind transition metal
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Flavonoids are a class of natural phenolic compounds that show antioxidant properties. Besides the known mechanisms of action of flavonoids (binding/inactivation of free radicals and other reactive oxygen species) that determine this effect, an important factor is their ability to bind transition metal ions. In this paper, we used a HPLC method with a prechromatographic reaction of a sample with Fe2+ ions (FeCA-HPLC) to characterize the Fe2+-chelating properties of individual compounds, their mixtures, and plant extracts. Using two classes of flavonoids (flavones, flavonols) the ability of compounds to bind Fe2+ ions due to a number of structural features of the compounds was shown. If the compounds possessed Fe2+-chelating properties, the decrease in the area of the chromatographic peaks on the chromatogram was marked. By comparing the resulting chromatogram with that of the untreated sample, it was possible to estimate the value of the effect. Application of this method for the analysis of plant extracts representing a mixture of substances allows determination of the compounds that have the greatest influence on the Fe2+-chelating activity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle In Vitro Antioxidant and Antiproliferative Activities of Methanolic Plant Part Extracts of Theobroma cacao
Molecules 2014, 19(11), 18317-18331; doi:10.3390/molecules191118317
Received: 10 September 2014 / Revised: 16 October 2014 / Accepted: 17 October 2014 / Published: 10 November 2014
Cited by 9 | PDF Full-text (242 KB) | HTML Full-text | XML Full-text
Abstract
The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances
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The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50) was 358.3 ± 7.0 µg/mL and total phenolic content was 22.0 ± 1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4% ± 1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50) = 41.4 ± 3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Chemical Compositions, Chromatographic Fingerprints and Antioxidant Activities of Andrographis Herba
Molecules 2014, 19(11), 18332-18350; doi:10.3390/molecules191118332
Received: 24 September 2014 / Revised: 3 November 2014 / Accepted: 6 November 2014 / Published: 10 November 2014
Cited by 7 | PDF Full-text (568 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This paper describes the development of an HPLC-UV-MS method for quantitative determination of andrographolide and dehydroandrographolide in Andrographis Herba and establishment of its chromatographic fingerprint. The method was validated for linearity, limit of detection and quantification, inter- and intra-day precisions, repeatability, stability and
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This paper describes the development of an HPLC-UV-MS method for quantitative determination of andrographolide and dehydroandrographolide in Andrographis Herba and establishment of its chromatographic fingerprint. The method was validated for linearity, limit of detection and quantification, inter- and intra-day precisions, repeatability, stability and recovery. All the validation results of quantitative determination and fingerprinting methods were satisfactory. The developed method was then applied to assay the contents of andrographolide and dehydroandrographolide and to acquire the fingerprints of all the collected Andrographis Herba samples. Furthermore, similarity analysis and principal component analysis were used to reveal the similarities and differences between the samples on the basis of the characteristic peaks. More importantly, the DPPH free radical-scavenging and ferric reducing capacities of the Andrographis Herba samples were assayed. By bivariate correlation analysis, we found that six compounds are positively correlated to DPPH free radical scavenging and ferric reducing capacities, and four compounds are negatively correlated to DPPH free radical scavenging and ferric reducing capacities. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Femtosecond Laser Spectroscopy of the Rhodopsin Photochromic Reaction: A Concept for Ultrafast Optical Molecular Switch Creation (Ultrafast Reversible Photoreaction of Rhodopsin)
Molecules 2014, 19(11), 18351-18366; doi:10.3390/molecules191118351
Received: 8 October 2014 / Revised: 4 November 2014 / Accepted: 6 November 2014 / Published: 11 November 2014
Cited by 3 | PDF Full-text (1547 KB) | HTML Full-text | XML Full-text
Abstract
Ultrafast reverse photoreaction of visual pigment rhodopsin in the femtosecond time range at room temperature is demonstrated. Femtosecond two-pump probe experiments with a time resolution of 25 fs have been performed. The first рump pulse at 500 nm initiated cis-trans photoisomerization of rhodopsin
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Ultrafast reverse photoreaction of visual pigment rhodopsin in the femtosecond time range at room temperature is demonstrated. Femtosecond two-pump probe experiments with a time resolution of 25 fs have been performed. The first рump pulse at 500 nm initiated cis-trans photoisomerization of rhodopsin chromophore, 11-cis retinal, which resulted in the formation of the primary ground-state photoproduct within a mere 200 fs. The second pump pulse at 620 nm with a varying delay of 200 to 3750 fs relative to the first рump pulse, initiated the reverse phototransition of the primary photoproduct to rhodopsin. The results of this photoconversion have been observed on the differential spectra obtained after the action of two pump pulses at a time delay of 100 ps. It was found that optical density decreased at 560 nm in the spectral region of bathorhodopsin absorption and increased at 480 nm, where rhodopsin absorbs. Rhodopsin photoswitching efficiency shows oscillations as a function of the time delay between two рump pulses. The quantum yield of reverse photoreaction initiated by the second pump pulse falls within the range 15% ± 1%. The molecular mechanism of the ultrafast reversible photoreaction of visual pigment rhodopsin may be used as a concept for the development of an ultrafast optical molecular switch. Full article
(This article belongs to the Special Issue Molecular Switches)
Open AccessArticle Data-Driven Techniques for Detecting Dynamical State Changes in Noisily Measured 3D Single-Molecule Trajectories
Molecules 2014, 19(11), 18381-18398; doi:10.3390/molecules191118381
Received: 1 September 2014 / Revised: 28 October 2014 / Accepted: 29 October 2014 / Published: 12 November 2014
Cited by 6 | PDF Full-text (3710 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Optical microscopes and nanoscale probes (AFM, optical tweezers, etc.) afford researchers tools capable of quantitatively exploring how molecules interact with one another in live cells. The analysis of in vivo single-molecule experimental data faces numerous challenges due to the complex, crowded, and
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Optical microscopes and nanoscale probes (AFM, optical tweezers, etc.) afford researchers tools capable of quantitatively exploring how molecules interact with one another in live cells. The analysis of in vivo single-molecule experimental data faces numerous challenges due to the complex, crowded, and time changing environments associated with live cells. Fluctuations and spatially varying systematic forces experienced by molecules change over time; these changes are obscured by “measurement noise” introduced by the experimental probe monitoring the system. In this article, we demonstrate how the Hierarchical Dirichlet Process Switching Linear Dynamical System (HDP-SLDS) of Fox et al. [IEEE Transactions on Signal Processing 59] can be used to detect both subtle and abrupt state changes in time series containing “thermal” and “measurement” noise. The approach accounts for temporal dependencies induced by random and “systematic overdamped” forces. The technique does not require one to subjectively select the number of “hidden states” underlying a trajectory in an a priori fashion. The number of hidden states is simultaneously inferred along with change points and parameters characterizing molecular motion in a data-driven fashion. We use large scale simulations to study and compare the new approach to state-of-the-art Hidden Markov Modeling techniques. Simulations mimicking single particle tracking (SPT) experiments are the focus of this study. Full article
(This article belongs to the Special Issue Single Molecule Techniques)
Open AccessArticle Thermal Reactivity of Neutral and Oxidized Ferrocenyl-Substituted Enediynes
Molecules 2014, 19(11), 18399-18413; doi:10.3390/molecules191118399
Received: 18 September 2014 / Revised: 1 November 2014 / Accepted: 3 November 2014 / Published: 12 November 2014
Cited by 2 | PDF Full-text (1559 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The coupling of two equivalents of ethynylferrocene (2) with one equivalent of 1,2-diiodocyclohexene (1) and 1,2-diiodobenzene (4) using Sonogashira cross-coupling conditions led to 1,2-bis(ferrocenylethynyl)cyclohexene (3) and 1,2-bis(ferrocenylethy­nyl)benzene (5), respectively. At high temperatures enediynes
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The coupling of two equivalents of ethynylferrocene (2) with one equivalent of 1,2-diiodocyclohexene (1) and 1,2-diiodobenzene (4) using Sonogashira cross-coupling conditions led to 1,2-bis(ferrocenylethynyl)cyclohexene (3) and 1,2-bis(ferrocenylethy­nyl)benzene (5), respectively. At high temperatures enediynes 3 and 5 showed exothermic signals in differential scanning calorimetry (DSC) measurements, suggestive of intramolecular diradicaloid ring formation (Bergman (C1−C6) or Schreiner-Pascal (C1−C5) cyclizations). The oxidation of 3 and 5 to the mono-oxidized enediynes 3+ and 5+ decreased the onset temperatures drastically. Equally, 1-ferrocenylethynyl-2-(p-nitro-phenyl)ethynylbenzene (8) displayed a significant decrease in the onset temperature after oxidation to 8+. Because the insoluble nature of the polymeric material formed in the thermolysis of the oxidized enediynes prevented characterization, the origin of this drastic effect was studied by DFT. Contrary to expectations, one-electron oxidation does not lower the barrier for intramolecular cyclization. Rather, the computations suggest that the polymerization is initiated by a bimolecular process. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle Augmenting the Antifungal Activity of an Oxidizing Agent with Kojic Acid: Control of Penicillium Strains Infecting Crops
Molecules 2014, 19(11), 18448-18464; doi:10.3390/molecules191118448
Received: 24 September 2014 / Revised: 4 November 2014 / Accepted: 5 November 2014 / Published: 12 November 2014
Cited by 3 | PDF Full-text (1237 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oxidative treatment is one of the strategies for preventing Penicillium contamination in crops/foods. The antifungal efficacy of hydrogen peroxide (H2O2; oxidant) was investigated in Penicillium strains by using kojic acid (KA) as a chemosensitizing agent, which can enhance the
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Oxidative treatment is one of the strategies for preventing Penicillium contamination in crops/foods. The antifungal efficacy of hydrogen peroxide (H2O2; oxidant) was investigated in Penicillium strains by using kojic acid (KA) as a chemosensitizing agent, which can enhance the susceptibility of pathogens to antifungal agents. Co-application of KA with H2O2 (chemosensitization) resulted in the enhancement of antifungal activity of either compound, when compared to the independent application of each agent alone. Of note, heat enhanced the activity of H2O2 to a greater extent during chemosensitization, whereby the minimum inhibitory or minimum fungicidal concentrations of H2O2 was decreased up to 4 or 13 fold, respectively, at 35–45 °C (heat), when compared to that at 28 °C (normal growth temperature). However, heat didn’t increase the antifungal activity of KA, indicating specificity exists between heat and types of antifungals applied. The effect of chemosensitization was also strain-specific, where P. expansum (both parental and fludioxonil-resistant mutants) or P. italicum 983 exhibited relatively higher susceptibility to the chemosensitization, comparing to other Penicillium strains tested. Collectively, chemosensitization can serve as a potent antifungal strategy to lower effective dosages of toxic antifungal substances, such as H2O2. This can lead to coincidental lowering of environmental and health risks. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Ampelopsis brevipedunculata Extract Prevents Bone Loss by Inhibiting Osteoclastogenesis in Vitro and in Vivo
Molecules 2014, 19(11), 18465-18478; doi:10.3390/molecules191118465
Received: 30 September 2014 / Revised: 28 October 2014 / Accepted: 10 November 2014 / Published: 12 November 2014
Cited by 2 | PDF Full-text (5066 KB) | HTML Full-text | XML Full-text
Abstract
Osteoclasts play a critical role in bone resorbing disorders such as osteoporosis, periodontitis, and rheumatoid arthritis. Therefore, discovery of agents capable of suppressing osteoclast differentiation may aid the development of a therapeutic access for the treatment of pathological bone loss. Ampelopsis brevipedunculata has
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Osteoclasts play a critical role in bone resorbing disorders such as osteoporosis, periodontitis, and rheumatoid arthritis. Therefore, discovery of agents capable of suppressing osteoclast differentiation may aid the development of a therapeutic access for the treatment of pathological bone loss. Ampelopsis brevipedunculata has been used as herbal folk medicine to treat liver diseases and inflammation in Asia. However, its effects on osteoclast differentiation are unknown. We were aimed to investigate the anti-osteoclastogenic activity in vitro and in vivo and to elucidate the underlying mechanism of Ampelopsis brevipedunculata extract (ABE). In this study, ABE inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation, the formation of filamentous actin rings and the bone resorbing activity of mature osteoclasts. ABE inhibited RANKL-induced p38 and IκB phosphorylation and IκB degradation. Also, ABE suppressed the mRNA and protein expression of nuclear factor of activated T cells c1 (NFATc1) and c-Fos, and the mRNA expression of genes required for cell fusion and bone resorption, such as osteoclast-associated receptor (OSCAR), tartrate resistant acid phosphatase (TRAP), cathepsin K, dendritic cell-specific transmembrane protein (DC-STAMP), β3-integrin and osteoclast stimulatory transmembrane protein (OC-STAMP). Furthermore, results of micro-CT and histologic analysis indicated that ABE remarkably prevented lipopolysaccharide (LPS)-induced bone erosion. These results demonstrate that ABE prevents LPS-induced bone erosion through inhibition of osteoclast differentiation and function, suggesting the promise of ABE as a potential cure for various osteoclast-associated bone diseases. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle External Application of the Volatile Oil from Blumea balsamifera May Be Safe for Liver — A Study on Its Chemical Composition and Hepatotoxicity
Molecules 2014, 19(11), 18479-18492; doi:10.3390/molecules191118479
Received: 11 September 2014 / Revised: 4 November 2014 / Accepted: 5 November 2014 / Published: 13 November 2014
Cited by 6 | PDF Full-text (3496 KB) | HTML Full-text | XML Full-text
Abstract
Ainaxiang (Blumea balsamifera), also known as Sambong, is an important ancient medicinal herb in Southeast Asia. It is rich in volatile oil, and still widely used nowadays for skin wound healing and treatment of sore throats. We analyzed the volatile oil
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Ainaxiang (Blumea balsamifera), also known as Sambong, is an important ancient medicinal herb in Southeast Asia. It is rich in volatile oil, and still widely used nowadays for skin wound healing and treatment of sore throats. We analyzed the volatile oil from Blumea balsamifera (BB oil) by gas chromatography-mass spectrometry (GC-MS). Forty one components, including l-borneol, were identified. Next, the damaging effects of BB oil diluted with olive oil on liver at different concentrations (100%, 50%, 20%), were evaluated, using both normal and wounded skin. Plasma ALT, AST, ALP and TBili were assessed, along with liver histopathology. The results showed that serum levels of liver toxicity markers in the high concentration groups (100% w/v) increased compared with control groups, whereas no significant changes was observed in histopathology of liver samples. In the wound groups, treatment with BB oil resulted in a decrease in serum toxicity index, compared with normal animal groups. This study confirms the safety of short term BB oil consumption, though high BB oil doses may lead to mild liver injury and this response might be weakened in the case of cutaneous wounds. These results are expected to be helpful for guiding appropriate therapeutic use of BB oil. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Pterocarpan-Enriched Soy Leaf Extract Ameliorates Insulin Sensitivity and Pancreatic β-Cell Proliferation in Type 2 Diabetic Mice
Molecules 2014, 19(11), 18493-18510; doi:10.3390/molecules191118493
Received: 2 September 2014 / Revised: 4 November 2014 / Accepted: 7 November 2014 / Published: 13 November 2014
Cited by 11 | PDF Full-text (4840 KB) | HTML Full-text | XML Full-text
Abstract
In Korea, soy (Glycine max (L.) Merr.) leaves are eaten as a seasonal vegetable or pickled in soy sauce. Ethyl acetate extracts of soy leaves (EASL) are enriched in pterocarpans and have potent α-glucosidase inhibitory activity. This study investigated the molecular mechanisms
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In Korea, soy (Glycine max (L.) Merr.) leaves are eaten as a seasonal vegetable or pickled in soy sauce. Ethyl acetate extracts of soy leaves (EASL) are enriched in pterocarpans and have potent α-glucosidase inhibitory activity. This study investigated the molecular mechanisms underlying the anti-diabetic effect of EASL in C57BL/6J mice with high-fat diet (HFD)-induced type 2 diabetes. Mice were randomly divided into normal diet (ND), HFD (60 kcal% fat diet), EASL (HFD with 0.56% (wt/wt) EASL), and Pinitol (HFD with 0.15% (wt/wt) pinitol) groups. Weight gain and abdominal fat accumulation were significantly suppressed by EASL. Levels of plasma glucose, HbA1c, and insulin in the EASL group were significantly lower than those of the HFD group, and the pancreatic islet of the EASL group had greater size than those of the HFD group. EASL group up-regulated neurogenin 3 (Ngn3), paired box 4 (Pax4), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), which are markers of pancreatic cell development, as well as insulin receptor substrate 1 (IRS1), IRS2, and glucose transporter 4 (GLUT4), which are related to insulin sensitivity. Furthermore, EASL suppressed genes involved in hepatic gluconeogenesis and steatosis. These results suggest that EASL improves plasma glucose and insulin levels in mice with HDF-induced type 2 diabetes by regulating β-cell proliferation and insulin sensitivity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Proteolysis, NaOH and Ultrasound-Enhanced Extraction of Anticoagulant and Antioxidant Sulfated Polysaccharides from the Edible Seaweed, Gracilaria birdiae
Molecules 2014, 19(11), 18511-18526; doi:10.3390/molecules191118511
Received: 16 August 2014 / Revised: 22 October 2014 / Accepted: 27 October 2014 / Published: 13 November 2014
Cited by 11 | PDF Full-text (666 KB) | HTML Full-text | XML Full-text
Abstract
The sulfated polysaccharides (SP) from the edible red seaweed, Gracilaria birdiae, were obtained using five different extraction conditions: Gracilaria birdiae 1 (GB1)-water; GB1s-water/sonication; GB1sp-water/sonication/proteolysis; GB2s-NaOH/sonication; and GB2sp-NaOH/sonication/proteolysis. The yield (g) increased in the following order: GB2sp > GB1sp > GB2s > GB1s
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The sulfated polysaccharides (SP) from the edible red seaweed, Gracilaria birdiae, were obtained using five different extraction conditions: Gracilaria birdiae 1 (GB1)-water; GB1s-water/sonication; GB1sp-water/sonication/proteolysis; GB2s-NaOH/sonication; and GB2sp-NaOH/sonication/proteolysis. The yield (g) increased in the following order: GB2sp > GB1sp > GB2s > GB1s > GB1. However, the amount of SP extracted increased in a different way: GB2sp > GB1 > GB1sp > GB1s > GB2s. Infrared and electrophoresis analysis showed that all conditions extracted the same SP. In addition, monosaccharide composition showed that ultrasound promotes the extraction of polysaccharides other than SP. In the prothrombin time (PT) test, which evaluates the extrinsic coagulation pathway, none of the samples showed anticoagulant activity. While in the activated partial thromboplastin time (aPTT) test, which evaluates the intrinsic coagulation pathway, all samples showed anticoagulant activity, except GB2s. The aPTT activity decreased in the order of GB1sp > GB2sp > GB1 > GB1s > GB2s. The total capacity antioxidant (TCA) of the SP was also affected by extraction condition, since GB2s and GB1 showed lower activity in comparison to the other conditions. In conclusion, the conditions of SP extraction influence their biological activities and chemical composition. The data revealed that NaOH/sonication/proteolysis was the best condition to extract anticoagulant and antioxidant SPs from Gracilaria birdiae. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Novel Polycarbo-Substituted Alkyl (Thieno[3,2-c]quinoline)-2-Carboxylates: Synthesis and Cytotoxicity Studies
Molecules 2014, 19(11), 18527-18542; doi:10.3390/molecules191118527
Received: 8 September 2014 / Revised: 6 November 2014 / Accepted: 7 November 2014 / Published: 13 November 2014
Cited by 1 | PDF Full-text (751 KB) | HTML Full-text | XML Full-text
Abstract
Direct one-pot base-promoted conjugate addition–elimination of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with methyl mercaptoacetate and subsequent cyclization afforded methyl [(6,8-dibromothieno[3,2-c]quinoline)]-2-carboxylate. The latter undergoes Suzuki-Miyaura cross-coupling with arylboronic acids to yield exclusively the corresponding alkyl [(6,8-diarylthieno[3,2-c]quinoline)]-2-carboxylates,. The cytotoxicity of the prepared compounds was evaluated
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Direct one-pot base-promoted conjugate addition–elimination of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with methyl mercaptoacetate and subsequent cyclization afforded methyl [(6,8-dibromothieno[3,2-c]quinoline)]-2-carboxylate. The latter undergoes Suzuki-Miyaura cross-coupling with arylboronic acids to yield exclusively the corresponding alkyl [(6,8-diarylthieno[3,2-c]quinoline)]-2-carboxylates,. The cytotoxicity of the prepared compounds was evaluated against the human breast cancer cell line MCF-7 using the MTT assay. The effects of compounds 2, 3c and 4d on cell kinetics were further determined using the xCELLigence Real Time Cell Analysis (RTCA) system. In both the MTT assay and Real Time Cell Analysis, the compounds inhibited cancer cell growth in a dose- and time-dependent manner. Furthermore, on the basis of the calculated LC50 values, the compounds compared favourably with nocodazole, a well-established anticancer drug. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle In Vitro Proliferation and Production of Cytokine and IgG by Human PBMCs Stimulated with Polysaccharide Extract from Plants Endemic to Gabon
Molecules 2014, 19(11), 18543-18557; doi:10.3390/molecules191118543
Received: 6 August 2014 / Revised: 7 October 2014 / Accepted: 8 October 2014 / Published: 13 November 2014
Cited by 1 | PDF Full-text (586 KB) | HTML Full-text | XML Full-text
Abstract
Polysaccharides were extracted from seven plants endemic to Gabon to study their potential immunological activities. Peripheral blood mononuclear cell (PBMC) (5 × 105 cells/mL) proliferation, cytokine and immunoglobulin G (IgG) assays were performed after stimulation with different concentrations of polysaccharide fractions compared
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Polysaccharides were extracted from seven plants endemic to Gabon to study their potential immunological activities. Peripheral blood mononuclear cell (PBMC) (5 × 105 cells/mL) proliferation, cytokine and immunoglobulin G (IgG) assays were performed after stimulation with different concentrations of polysaccharide fractions compared with lipopolysaccharides (LPS) and concanavalin A (ConA) from healthy volunteers. The culture supernatants were used for cytokine and IgG detection by enzyme-linked immunosorbent assay (ELISA). The results show that pectin and hemicellulose extracts from Uvaria klainei, Petersianthus macrocarpus, Trichoscypha addonii, Aphanocalyx microphyllus, Librevillea klaineana, Neochevalierodendron stephanii and Scorodophloeus zenkeri induced production levels that were variable from one individual to another for IL-12 (3–40 pg/mL), IL-10 (6–443 pg/mL), IL-6 (7–370 pg/mL), GM-CSF (3–170 pg/mL) and IFN-γ (5–80 pg/mL). Only hemicelluloses from Aphanocalyx microphyllus produce a small amount of IgG (OD = 0.034), while the proliferation of cells stimulated with these polysaccharides increased up to 318% above the proliferation of unstimulated cells. However, this proliferation of PBMCs was abolished when the pectin of some of these plants was treated with endopolygalacturonase (p < 0.05), but the trend of cytokine synthesis remained the same, both before and after enzymatic treatment or saponification. This study suggests that these polysaccharides stimulate cells in a structure-dependent manner. The rhamnogalacturonan-I (RGI) fragment alone was not able to induce the proliferation of PBMC. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Synthetic Genistein Glycosides Inhibiting EGFR Phosphorylation Enhance the Effect of Radiation in HCT 116 Colon Cancer Cells
Molecules 2014, 19(11), 18558-18573; doi:10.3390/molecules191118558
Received: 31 August 2014 / Revised: 5 November 2014 / Accepted: 7 November 2014 / Published: 13 November 2014
Cited by 9 | PDF Full-text (732 KB) | HTML Full-text | XML Full-text
Abstract
The need to find new EGFR inhibitors for use in combination with radiotherapy in the treatment of solid tumors has drawn our attention to compounds derived from genistein, a natural isoflavonoid. The antiproliferative potential of synthetic genistein derivatives used alone or in combination
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The need to find new EGFR inhibitors for use in combination with radiotherapy in the treatment of solid tumors has drawn our attention to compounds derived from genistein, a natural isoflavonoid. The antiproliferative potential of synthetic genistein derivatives used alone or in combination with ionizing radiation was evaluated in cancer cell lines using clonogenic assay. EGFR phosphorylation was assessed with western blotting. Genistein derivatives inhibited clonogenic growth of HCT 116 cancer cells additively or synergistically when used in combination with ionizing radiation, and decreased EGFR activation. Our preclinical evaluation of genistein-derived EGFR inhibitors suggests that these compounds are much more potent sensitizers of cells to radiation than the parent isoflavonoid, genistein and indicate that these compounds may be useful in the treatment of colon cancer with radiation therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle The Crystal Structure and Morphology of 2,4,6,8,10,12-Hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) p-Xylene Solvate: A Joint Experimental and Simulation Study
Molecules 2014, 19(11), 18574-18589; doi:10.3390/molecules191118574
Received: 7 September 2014 / Revised: 23 October 2014 / Accepted: 24 October 2014 / Published: 13 November 2014
Cited by 9 | PDF Full-text (3165 KB) | HTML Full-text | XML Full-text
Abstract
The crystal structure of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaiso-wurtzitane (CL-20) p-xylene solvate, and the solvent effects on the crystal faces of CL-20 were studied through a combined experimental and theoretical method. The properties were analyzed by thermogravimetry-differential scanning calorimetry (TG-DSC), Fourier transform infrared spectroscopy (FTIR) and
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The crystal structure of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaiso-wurtzitane (CL-20) p-xylene solvate, and the solvent effects on the crystal faces of CL-20 were studied through a combined experimental and theoretical method. The properties were analyzed by thermogravimetry-differential scanning calorimetry (TG-DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD).The growth morphology of CL-20p-xylene solvate crystal was predicted with a modified attachment energy model. The crystal structure of CL-20p-xylene solvate belonged to the Pbca space group with the unit cell parameters, a = 8.0704(12) Å, b=13.4095(20) Å, c = 33.0817(49) Å, and Z = 4, which indicated that the p-xylene solvent molecules could enter the crystal lattice of CL-20 and thus the CL-20 p-xylene solvate is formed. According to the solvent-effected attachment energy calculations, (002) and (11−1) faces should not be visible at all, while the percentage area of the (011) face could be increased from 7.81% in vacuum to 12.51% in p-xylene solution. The predicted results from the modified attachment energy model agreed very well with the observed morphology of crystals grown from p-xylene solution. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Effects of the Continuous Administration of an Agaricus blazei Extract to Rats on Oxidative Parameters of the Brain and Liver during Aging
Molecules 2014, 19(11), 18590-18603; doi:10.3390/molecules191118590
Received: 7 October 2014 / Revised: 6 November 2014 / Accepted: 7 November 2014 / Published: 13 November 2014
Cited by 3 | PDF Full-text (344 KB) | HTML Full-text | XML Full-text
Abstract
An investigation of the effects of an aqueous extract of Agaricus blazei, a medicinal mushroom, on the oxidative state of the brain and liver of rats during aging (7 to 23 months) was conducted. The treatment consisted in the daily intragastric administration
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An investigation of the effects of an aqueous extract of Agaricus blazei, a medicinal mushroom, on the oxidative state of the brain and liver of rats during aging (7 to 23 months) was conducted. The treatment consisted in the daily intragastric administration of 50 mg/kg of the extract. The A. blazei treatment tended to maintain the ROS contents of the brain and liver at lower levels, but a significant difference was found only at the age of 23 months and in the brain. The TBARS levels in the brain were maintained at lower levels by the A. blazei treatment during the whole aging process with a specially pronounced difference at the age of 12 months. The total antioxidant capacity in the brain was higher in treated rats only at the age of 12 months. Compared with previous studies in which old rats (21 months) were treated during a short period of 21 days with 200 mg/kg, the effects of the A. blazei extract in the present study tended to be less pronounced. The results also indicate that the long and constant treatment presented a tendency of becoming less effective at ages above 12 months. Full article
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
Open AccessArticle Mild Conditions for Deuteration of Primary and Secondary Arylamines for the Synthesis of Deuterated Optoelectronic Organic Molecules
Molecules 2014, 19(11), 18604-18617; doi:10.3390/molecules191118604
Received: 5 September 2014 / Revised: 29 October 2014 / Accepted: 4 November 2014 / Published: 13 November 2014
Cited by 4 | PDF Full-text (261 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based
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Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based on the difference in the scattering length density between protonated and deuterated compounds. Here we report mild deuteration conditions utilising standard laboratory glassware for the deuteration of: diphenylamine, N-phenylnaphthylamine, N-phenyl-o-phenylenediamine and 1-naphthylamine (via H/D exchange in D2O at 80 °C, catalysed by Pt/C and Pd/C). These conditions were not successful in the deuteration of triphenylamine or N,N-dimethylaniline, suggesting that these mild conditions are not suitable for the deuteration of tertiary arylamines, but are likely to be applicable for the deuteration of other primary and secondary arylamines. The deuterated arylamines can then be used for synthesis of larger organic molecules or polymers with optoelectronic applications. Full article
(This article belongs to the Special Issue Deuterated Molecules and Polymers for Neutron Studies)
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Open AccessArticle Synthesis and Biological Evaluation of 2-Phenoxyacetamide Analogues, a Novel Class of Potent and Selective Monoamine Oxidase Inhibitors
Molecules 2014, 19(11), 18620-18631; doi:10.3390/molecules191118620
Received: 11 August 2014 / Revised: 6 November 2014 / Accepted: 7 November 2014 / Published: 14 November 2014
Cited by 3 | PDF Full-text (327 KB) | HTML Full-text | XML Full-text
Abstract
Monoamine oxidases (EC 1.4.3.4; MAOs), a family of FAD-containing enzymes, is an important target for antidepressant drugs. In this paper, a series of 2-phenoxyacetamide analogues were synthesized, and their inhibitory potency towards monoamine oxidases A (MAO-A) and B (MAO-B) were evaluated using enzyme
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Monoamine oxidases (EC 1.4.3.4; MAOs), a family of FAD-containing enzymes, is an important target for antidepressant drugs. In this paper, a series of 2-phenoxyacetamide analogues were synthesized, and their inhibitory potency towards monoamine oxidases A (MAO-A) and B (MAO-B) were evaluated using enzyme and cancer cell lysate. 2-(4-Methoxyphenoxy)acetamide (compound 12) (SI = 245) and (2-(4-((prop-2-ynylimino)methyl)phenoxy)acetamide (compound 21) (IC50MAO-A = 0.018 μM, IC50MAO-B = 0.07 μM) were successfully identified as the most specific MAO-A inhibitor, and the most potent MAO-A/-B inhibitor, respectively. The inhibitory activities of these two compounds in living cells were also further evaluated utilizing HepG2 and SHSY-5Y cell lysates. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and in Vitro Antitumor Activity of a Novel Series of 2-Pyrazoline Derivatives Bearing the 4-Aryloxy-7-chloroquinoline Fragment
Molecules 2014, 19(11), 18656-18675; doi:10.3390/molecules191118656
Received: 24 September 2014 / Revised: 4 November 2014 / Accepted: 6 November 2014 / Published: 14 November 2014
Cited by 10 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text
Abstract
A new series of NH-pyrazoline derivatives 6 was synthesized by cyclocondensation reaction of novel [(7-chloroquinolin-4-yl)oxy]chalcones 5 with hydrazine hydrate. The treatment of pyrazolines 6 with acetic anhydride or formic acid yielded the N-acetyl- or N-formylpyrazoline derivatives 78,
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A new series of NH-pyrazoline derivatives 6 was synthesized by cyclocondensation reaction of novel [(7-chloroquinolin-4-yl)oxy]chalcones 5 with hydrazine hydrate. The treatment of pyrazolines 6 with acetic anhydride or formic acid yielded the N-acetyl- or N-formylpyrazoline derivatives 78, respectively. These novel 2-pyrazoline derivatives 68 were evaluated by the U.S. National Cancer Institute (NCI). Compounds 7b,d,f and 8c,f showed remarkable antitumor activity against 58 cancer cell lines, with the most important GI50 values from in vitro assays ranging from 0.48 to 1.66 μM. The 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline fragment are thus considered to be useful leads for the rational design of new antitumor agents. Full article
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Open AccessArticle Design and Synthesis of Isosteviol Triazole Conjugates for Cancer Therapy
Molecules 2014, 19(11), 18676-18689; doi:10.3390/molecules191118676
Received: 13 October 2014 / Revised: 6 November 2014 / Accepted: 6 November 2014 / Published: 14 November 2014
Cited by 10 | PDF Full-text (649 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by
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One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using “click” chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development. Full article
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Open AccessArticle The Antiosteoporotic Activity of Central-Icaritin (CIT) on Bone Metabolism of Ovariectomized Rats
Molecules 2014, 19(11), 18690-18704; doi:10.3390/molecules191118690
Received: 22 September 2014 / Revised: 23 October 2014 / Accepted: 29 October 2014 / Published: 14 November 2014
Cited by 7 | PDF Full-text (1594 KB) | HTML Full-text | XML Full-text
Abstract
Central-icaritin (CIT) is a flavonoid aglycone first discovered in our laboratory, which is an isomeric aglycone of icaritin (IT). We wanted to know whether CIT also had anti-osteoporosis activity. In this study, CIT was investigated in an ovariectomized rat (OVX) model. Fifty-six 6-month
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Central-icaritin (CIT) is a flavonoid aglycone first discovered in our laboratory, which is an isomeric aglycone of icaritin (IT). We wanted to know whether CIT also had anti-osteoporosis activity. In this study, CIT was investigated in an ovariectomized rat (OVX) model. Fifty-six 6-month old female Sprague-Dawley rats were randomly assigned to sham operated group (Sham) and six OVX subgroups (n = 8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), icaritin (IT, 40 mg/kg body weight/day), estradiol valerate (EV, 100 μg/kg body weight/day) or CIT (10, 20, and 40 mg/kg body weight/day) for 12 weeks, respectively. Then, the serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone immunohistochemistry and related protein and gene expressions were evaluated. In OVX rats, the increases of body weight, HOP, AKP, and TRACP5b levels, and the decreases of uterus wet weight, femurs weight, BMD, serum OPG/RANKL and OCN were significantly inhibited by CIT treatment. Micro-CT analysis results showed that CIT apparently enhanced trabecular bone compared with the OVX group (p < 0.05). Total femur BMD and biomechanical strength of tibia were significantly improved (p < 0.05) after 12 weeks of CIT administration. In addition, the CIT administration also significantly enhanced the OPG expression, whereas reduced the RANKL expression in femurs according to RT-PCR, western blot assays and immunohistochemical evaluation. CIT had the antiosteoporotic activity, and its antiosteoporotic effects in OVX rats may be stronger than that of IT. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Removing Tannins from Medicinal Plant Extracts Using an Alkaline Ethanol Precipitation Process: A Case Study of Danshen Injection
Molecules 2014, 19(11), 18705-18720; doi:10.3390/molecules191118705
Received: 21 August 2014 / Revised: 12 October 2014 / Accepted: 7 November 2014 / Published: 14 November 2014
Cited by 5 | PDF Full-text (524 KB) | HTML Full-text | XML Full-text
Abstract
The alkaline ethanol precipitation process is investigated as an example of a technique for the removal of tannins extracted from Salviae miltiorrhizae Radix et Rhizoma for the manufacture of Danshen injection. More than 90% of the tannins can be removed. However, the recoveries
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The alkaline ethanol precipitation process is investigated as an example of a technique for the removal of tannins extracted from Salviae miltiorrhizae Radix et Rhizoma for the manufacture of Danshen injection. More than 90% of the tannins can be removed. However, the recoveries of danshensu, rosmarinic acid, and salvianolic acid B were less than 60%. Total tannin removal increased as the refrigeration temperature decreased or the amount of NaOH solution added increased. Phenolic compound recoveries increased as refrigeration temperature increased or the amount of NaOH solution added decreased. When operated at a low refrigeration temperature, a relative high separation selectivity can be realized. Phenolic compound losses and tannin removal were mainly caused by precipitation. The formation of phenol salts, whose solubility is small in the mixture of ethanol and water used, is probably the reason for the precipitation. A model considering dissociation equilibrium and dissolution equilibrium was established. Satisfactory correlation results were obtained for phenolic compound recoveries and total tannin removal. Two important parameters in the model, which are the water content and pH value of alkaline supernatant, are suggested to be monitored and controlled to obtain high batch-to-batch consistency. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Methanolic Extracts of Solieria robusta Inhibits Proliferation of Oral Cancer Ca9-22 Cells via Apoptosis and Oxidative Stress
Molecules 2014, 19(11), 18721-18732; doi:10.3390/molecules191118721
Received: 10 October 2014 / Revised: 7 November 2014 / Accepted: 10 November 2014 / Published: 14 November 2014
Cited by 16 | PDF Full-text (581 KB) | HTML Full-text | XML Full-text
Abstract
Many red algae-derived natural products are known to have anticancer effects. The biological functions of the red alga Solieria robusta from the Karachi coast (Pakistan) remain unclear. Here, we prepared a methanolic extracts of S. robusta (MESR) to examine its possible anti-oral
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Many red algae-derived natural products are known to have anticancer effects. The biological functions of the red alga Solieria robusta from the Karachi coast (Pakistan) remain unclear. Here, we prepared a methanolic extracts of S. robusta (MESR) to examine its possible anti-oral cancer effects and the corresponding mechanism of action. Cell viability of MESR-incubated oral cancer Ca9-22 cells was dose-responsively decreased (p < 0.001). According to a propidium iodide (PI)-based assay the cell cycle distribution was dramatically changed, especially for subG1 accumulation. Annexin V/PI assay of apoptosis using flow cytometry also showed that MESR-incubated Ca9-22 cells were dose-responsively increased (p < 0.001). For evaluation of oxidative stress in MESR-incubated Ca9-22 cells, we found that reactive oxygen species (ROS) were overexpressed dose- and time-responsively and mitochondrial depolarization was also increased (p < 0.001). Taken together, MESR showed inhibitory effects on oral cancer proliferation coupled with apoptosis and oxidative stress. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist
Molecules 2014, 19(11), 18733-18746; doi:10.3390/molecules191118733
Received: 9 October 2014 / Revised: 6 November 2014 / Accepted: 7 November 2014 / Published: 14 November 2014
Cited by 9 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs
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The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Curcumin Protects against CCl4-Induced Liver Fibrosis in Rats by Inhibiting HIF-1α Through an ERK-Dependent Pathway
Molecules 2014, 19(11), 18767-18780; doi:10.3390/molecules191118767
Received: 4 September 2014 / Revised: 21 October 2014 / Accepted: 27 October 2014 / Published: 17 November 2014
Cited by 11 | PDF Full-text (4460 KB) | HTML Full-text | XML Full-text
Abstract
The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of
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The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway. Full article
(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)
Open AccessArticle Kinetics of Glycoxidation of Bovine Serum Albumin by Glucose, Fructose and Ribose and Its Prevention by Food Components
Molecules 2014, 19(11), 18828-18849; doi:10.3390/molecules191118828
Received: 12 October 2014 / Revised: 9 November 2014 / Accepted: 12 November 2014 / Published: 17 November 2014
Cited by 17 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to compare the kinetics of the glycoxidation of bovine serum albumin (BSA) as a model protein by three sugars: glucose, fructose and ribose, using fluorometric measurements of the content of advanced glycation end products (AGEs), protein-bound fructosamine,
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The aim of this study was to compare the kinetics of the glycoxidation of bovine serum albumin (BSA) as a model protein by three sugars: glucose, fructose and ribose, using fluorometric measurements of the content of advanced glycation end products (AGEs), protein-bound fructosamine, dityrosine, N'-formylkynurenine, kynurenine, tryptophan, the content of advanced oxidation protein products (AOPP), protein carbonyl groups, as well as thiol groups. Moreover, the levels of glycoalbumin and AGEs were determined by using an enzyme-linked immunosorbent assay. Based on the kinetic results, the optimal incubation time for studies of the modification of the glycoxidation rate by additives was chosen, and the effects of 25 compounds of natural origin on the glycoxidation of BSA induced by various sugars were examined. The same compounds were found to have different effects on glycoxidation induced by various sugars, which suggests caution in extrapolation from experiments based on one sugar to other sugars. From among the compounds tested, the most effective inhibitors of glycoxidation were: polyphenols, pyridoxine and 1-cyano-4-hydroxycinnamic acid. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Profiling the Metabolism of Astragaloside IV by Ultra Performance Liquid Chromatography Coupled with Quadrupole/Time-of-Flight Mass Spectrometry
Molecules 2014, 19(11), 18881-18896; doi:10.3390/molecules191118881
Received: 24 September 2014 / Revised: 5 November 2014 / Accepted: 5 November 2014 / Published: 17 November 2014
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Abstract
Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological
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Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological actions and pharmacology. In the present study, an ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based approach was developed to profile the metabolites of astragaloside IV in rat plasma, bile, urine and feces samples. Twenty-two major metabolites were detected. The major components found in plasma, bile, urine and feces included the parent chemical and phases I and II metabolites. The major metabolic reactions of astragaloside IV were hydrolysis, glucuronidation, sulfation and dehydrogenation. These results will help to improve understanding the metabolism and reveal the biotransformation profiling of astragaloside IV in vivo. The metabolic information obtained from our study will guide studies into the pharmacological activity and clinical safety of astragaloside IV. Full article
Open AccessArticle Synthesis, Characterization and Antimicrobial Evaluation of Some New Schiff, Mannich and Acetylenic Mannich Bases Incorporating a 1,2,4-Triazole Nucleus
Molecules 2014, 19(11), 18897-18910; doi:10.3390/molecules191118897
Received: 31 August 2014 / Revised: 29 October 2014 / Accepted: 3 November 2014 / Published: 18 November 2014
Cited by 8 | PDF Full-text (301 KB) | HTML Full-text | XML Full-text
Abstract
A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl2 furnished
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A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl2 furnished the desired acetylenic Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1H- and 13C-NMR) data and evaluated for their biological activities. Some of the compounds were found to exhibit significant antimicrobial activity. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Preparation of Rotenone Derivatives and in Vitro Analysis of Their Antimalarial, Antileishmanial and Selective Cytotoxic Activities
Molecules 2014, 19(11), 18911-18922; doi:10.3390/molecules191118911
Received: 26 August 2014 / Revised: 12 November 2014 / Accepted: 13 November 2014 / Published: 18 November 2014
Cited by 3 | PDF Full-text (261 KB) | HTML Full-text | XML Full-text
Abstract
Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC
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Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC50 of 19.0 µM against P. falciparum, and 127.2 µM against L. panamensis. Although chemical transformation does not improve its biological profile against P. falciparum, three of its derivatives showed a significant level of action within an adequate range of activity with EC50 values < 50.0 µM. This antiplasmodial activity was not due to red blood cell hemolysis, since LC50 was >>400 µM. On the other hand, all derivatives displayed a non-specific cytotoxicity on several cell lines and primary human cell cultures. Full article
Open AccessArticle Method Development and Validation for Pharmacokinetic and Tissue Distributions of Ellagic Acid Using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS)
Molecules 2014, 19(11), 18923-18935; doi:10.3390/molecules191118923
Received: 4 October 2014 / Revised: 11 November 2014 / Accepted: 11 November 2014 / Published: 18 November 2014
Cited by 12 | PDF Full-text (477 KB) | HTML Full-text | XML Full-text
Abstract
Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A
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Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A simple, rapid, sensitive and specific liquid chromatography–tandem mass spectrometry method to determine the ellagic acid in plasma and tissue samples was developed and validated. The separation was achieved using reversed-phase ultra-performance liquid chromatography (UPLC), and the mass spectrometric detection was achieved using heated electrospray ionization (negative mode) and multiple ion monitoring (m/z 301/229). A sample cleanup with a solid phase extraction (SPE) step prior to the UPLC-MS/MS analysis was also developed. The SPE and UPLC-MS/MS method established here was successfully applied to reveal the pharmacokinetic profiles and tissue distribution of ellagic acid. After oral administration dosing at 50 mg/kg, plasma levels of ellagic acid peaked at about 0.5 h, with Cmax value of 93.6 ng/mL, and the results showed that the ellagic acid was poorly absorbed after oral administration. The pharmacokinetic profile of ellagic acid fitted to a two-compartment model with t1/2α 0.25 h and t1/2β 6.86 h, respectively. Following oral administration, ellagic acid was detected in all examined tissues including kidney, liver, heart, lung and brain et al., and the highest levels were found in kidney and liver. Full article
Open AccessArticle Monoamine Oxidase Inhibitory Constituents of Propolis: Kinetics and Mechanism of Inhibition of Recombinant Human MAO-A and MAO-B
Molecules 2014, 19(11), 18936-18952; doi:10.3390/molecules191118936
Received: 22 July 2014 / Revised: 7 October 2014 / Accepted: 11 October 2014 / Published: 18 November 2014
Cited by 17 | PDF Full-text (1013 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Propolis is the resinous material that bees gather from leaf buds, flowers and vegetables. Propolis extracts contain constituents with a broad spectra of pharmacological properties and are important ingredients of popular dietary supplements. Propolis extracts were evaluated in vitro for inhibition of recombinant
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Propolis is the resinous material that bees gather from leaf buds, flowers and vegetables. Propolis extracts contain constituents with a broad spectra of pharmacological properties and are important ingredients of popular dietary supplements. Propolis extracts were evaluated in vitro for inhibition of recombinant human monoamine oxidase (MAO)-A and MAO-B. The dichloromethane extract of propolis showed potent inhibition of human MAO-A and MAO-B. Further fractionation identified the most active fractions as rich in flavonoids. Galangin and apigenin were identified as the principal MAO-inhibitory constituents. Inhibition of MAO-A by galangin was about 36 times more selective than MAO-B, while apigenin selectivity for MAO-A vs. MAO-B was about 1.7 fold. Apigenin inhibited MAO-B significantly more potently than galangin. Galangin and apigenin were further evaluated for kinetic characteristics and the mechanism for the enzymes’ inhibition. Binding of galangin and apigenin with MAO-A and -B was not time-dependent and was reversible, as suggested by enzyme-inhibitor binding and dissociation-dialysis assay. The inhibition kinetics studies suggested that galangin and apigenin inhibited MAO-A and -B by a competitive mechanism. Presence of prominent MAO inhibitory constituents in propolis products suggests their potential for eliciting pharmacological effects that might be useful in depression or other neurological disorders. The results may also have important implications in drug-dietary supplement interactions. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B
Molecules 2014, 19(11), 18953-18965; doi:10.3390/molecules191118953
Received: 19 October 2014 / Revised: 19 October 2014 / Accepted: 5 November 2014 / Published: 18 November 2014
Cited by 4 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis,
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Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, we reveal that they show better performance than HBTU in terms of preserving chiral integrity and coupling yields, but slightly worse performance than COMU. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle The Diterpenes Ovoideal A–G from Tirpitzia ovoidea
Molecules 2014, 19(11), 18966-18979; doi:10.3390/molecules191118966
Received: 23 September 2014 / Revised: 4 November 2014 / Accepted: 5 November 2014 / Published: 18 November 2014
Cited by 2 | PDF Full-text (399 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Seven new diterpenes, named ovoideal A (1), B (2), C (3), D (4), E (5), F (6) and G (7), have been isolated along with eleven known diterpenes 8
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Seven new diterpenes, named ovoideal A (1), B (2), C (3), D (4), E (5), F (6) and G (7), have been isolated along with eleven known diterpenes 818 from the petroleum ether soluble fraction of an ethanol extract of the aerial parts of Tirpitzia ovoidea. The structures of the new compounds were elucidated primarily by 1D and 2D NMR spectroscopy, as well as by the HR-ESI-MS spectrometry. All compounds were isolated from the Linaceae family for the first time. The in vitro cytotoxic activity of compounds 1, 35, 818 was evaluated against the Hela, HepG2 and K562 cell lines. Among them, compounds 3, 9, 11, 12, 13, 14, 15, 17, 18 showed moderate inhibitory activities. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Classification of Frankfurters by FT-Raman Spectroscopy and Chemometric Methods
Molecules 2014, 19(11), 18980-18992; doi:10.3390/molecules191118980
Received: 29 July 2014 / Revised: 7 October 2014 / Accepted: 21 October 2014 / Published: 18 November 2014
Cited by 4 | PDF Full-text (584 KB) | HTML Full-text | XML Full-text
Abstract
Frankfurters are widely consumed all over the world, and the production requires a wide range of meat and non-meat ingredients. Due to these characteristics, frankfurters are products that can be easily adulterated with lower value meats, and the presence of undeclared species. Adulterations
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Frankfurters are widely consumed all over the world, and the production requires a wide range of meat and non-meat ingredients. Due to these characteristics, frankfurters are products that can be easily adulterated with lower value meats, and the presence of undeclared species. Adulterations are often still difficult to detect, due the fact that the adulterant components are usually very similar to the authentic product. In this work, FT-Raman spectroscopy was employed as a rapid technique for assessing the quality of frankfurters. Based on information provided by the Raman spectra, a multivariate classification model was developed to identify the frankfurter type. The aim was to study three types of frankfurters (chicken, turkey and mixed meat) according to their Raman spectra, based on the fatty vibrational bands. Classification model was built using partial least square discriminant analysis (PLS-DA) and the performance model was evaluated in terms of sensitivity, specificity, accuracy, efficiency and Matthews’s correlation coefficient. The PLS-DA models give sensitivity and specificity values on the test set in the ranges of 88%–100%, showing good performance of the classification models. The work shows the Raman spectroscopy with chemometric tools can be used as an analytical tool in quality control of frankfurters. Full article
(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)
Open AccessArticle Study on the Cytotoxic Activity of Drimane Sesquiterpenes and Nordrimane Compounds against Cancer Cell Lines
Molecules 2014, 19(11), 18993-19006; doi:10.3390/molecules191118993
Received: 23 September 2014 / Revised: 27 October 2014 / Accepted: 3 November 2014 / Published: 18 November 2014
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Abstract
Twelve drimanes, including polygodial (1), isopolygodial (2), drimenol (3), confertifolin (4), and isodrimenin (5), were obtained from natural sources. Semi-synthetic derivatives 612 were obtained from 1 and 2, and cytotoxic
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Twelve drimanes, including polygodial (1), isopolygodial (2), drimenol (3), confertifolin (4), and isodrimenin (5), were obtained from natural sources. Semi-synthetic derivatives 612 were obtained from 1 and 2, and cytotoxic activity was evaluated in vitro against cancer cell lines (HT-29, MDA-MB231, DHF, MCF-7, PC-3, DU-145, and CoN). IC50 values were determined at concentrations of 12.5–100 µM of each compound for 72 h. In addition, it was found that polygodial (1), 8, and 12 induced changes in mitochondrial membrane permeability in CoN, MCF-7, and PC-3 cells. Full article
Open AccessArticle Essential Oil of Eucalyptus Gunnii Hook. As a Novel Source of Antioxidant, Antimutagenic and Antibacterial Agents
Molecules 2014, 19(11), 19007-19020; doi:10.3390/molecules191119007
Received: 5 September 2014 / Revised: 7 November 2014 / Accepted: 11 November 2014 / Published: 18 November 2014
Cited by 7 | PDF Full-text (259 KB) | HTML Full-text | XML Full-text
Abstract
The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and
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The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and α-pinene (14.12%) were the major compounds comprising almost 82% of total EO. EO exhibited moderate DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, with IC50 value of 7.19 µL/mL. The antimutagenic properties were assayed against the spontaneous and t-BOOH-induced mutagenesis in Escherichia coli IC202 oxyR mutant strain, deficient in removing radical oxygen species (ROS). Reduction of the spontaneous mutagenesis in the presence of E. gunnii EO was only slight, up to 12% at the highest concentration tested. However, when the oxidative mutagen was used, EO displayed more significant reduction of mutagenesis (maximum 23%) in a concentration dependent manner. Antibacterial activity was tested against the selected strains from ATTC and NCIB collections: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Micrococcus flavus, Klebsiella pneumoniae, and the two Escherichia coli strains from our laboratory collection (SY252 and IB112) using both the disk-diffusion and MIC assays. The greatest sensitivity was shown by M. flavus, K. pneumoniae and E. coli lpcA (MIC = 0.83 mg/mL), while the highest resistance was shown by E. coli (ATTC 25922) and S. epidermidis. This study represents the first report on chemical composition and biological activity of the Eucalyptus gunnii in the South Balkan region and beyond. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents
Molecules 2014, 19(11), 19021-19035; doi:10.3390/molecules191119021
Received: 13 August 2014 / Revised: 10 November 2014 / Accepted: 12 November 2014 / Published: 18 November 2014
Cited by 9 | PDF Full-text (302 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in
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A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (79, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 μM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines. Full article
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Open AccessArticle Antioxidant Mechanism of Rutin on Hypoxia-Induced Pulmonary Arterial Cell Proliferation
Molecules 2014, 19(11), 19036-19049; doi:10.3390/molecules191119036
Received: 26 August 2014 / Revised: 28 September 2014 / Accepted: 9 October 2014 / Published: 18 November 2014
Cited by 11 | PDF Full-text (2948 KB) | HTML Full-text | XML Full-text
Abstract
Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study,
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Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Biological Evaluation of New Pleuromutilin Derivatives as Antibacterial Agents
Molecules 2014, 19(11), 19050-19065; doi:10.3390/molecules191119050
Received: 23 October 2014 / Revised: 11 November 2014 / Accepted: 12 November 2014 / Published: 19 November 2014
Cited by 12 | PDF Full-text (2267 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus
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Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus were tested by the agar dilution method and Oxford cup assay. All the screened compounds displayed potent activity. Compound 6d was the most active antibacterial agent because of its lowest MIC value and largest inhibition zone. Docking experiments were performed to understand the possible mode of the interactions between the derivatives and 50S ribosomal subunit. Moreover, the absorption, distribution, metabolism, excretion and toxicity properties of the synthesized compounds were analyzed after prediction using the Advanced Chemistry Development/Percepta Platform available online. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts
Molecules 2014, 19(11), 19066-19077; doi:10.3390/molecules191119066
Received: 5 September 2014 / Revised: 12 November 2014 / Accepted: 13 November 2014 / Published: 19 November 2014
Cited by 19 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text
Abstract
BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed
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BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Composition and Antioxidant Activity of the Anthocyanins of the Fruit of Berberis heteropoda Schrenk
Molecules 2014, 19(11), 19078-19096; doi:10.3390/molecules191119078
Received: 16 October 2014 / Revised: 28 October 2014 / Accepted: 3 November 2014 / Published: 19 November 2014
Cited by 6 | PDF Full-text (604 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In present study, the anthocyanin composition and content of the fruit of B. heteropoda Schrenk were determined for the first time. The total anthocyanins were extracted from the fruit of B. heteropoda Schrenk using 0.5% HCl in 80% methanol and were then purified
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In present study, the anthocyanin composition and content of the fruit of B. heteropoda Schrenk were determined for the first time. The total anthocyanins were extracted from the fruit of B. heteropoda Schrenk using 0.5% HCl in 80% methanol and were then purified using an AB-8 macroporous resin column. The purified anthocyanin extract (PAE) was evaluated by high-performance liquid chromatography with a diode array detector (HPLC-DAD) and HPLC-high resolution-electrospray ionization-mass spectrometry (HPLC-HR-ESI-MS) under the same experimental conditions. The results revealed the presence of seven different anthocyanins. The major anthocyanins purified by preparative HPLC were confirmed to be delphinidin-3-O-glucopyranoside (30.3%), cyanidin-3-O-glucopyranoside (33.5%), petunidin-3-Ο-glucopyranoside (10.5%), peonidin-3-O-glucopyranoside (8.5%) and malvidin-3-O-glucopyranoside (13.8%) using HPLC-HR-ESI-MS and NMR spectroscopy. The total anthocyanin content was 2036.6 ± 2.2 mg/100 g of the fresh weight of B. heteropoda Schrenk fruit. In terms of its total reducing capacity assay, DPPH radical-scavenging activity assay, ferric-reducing antioxidant power (FRAP) assay and ABTS radical cation-scavenging activity assay, the PAE also showed potent antioxidant activity. The results are valuable for illuminating anthocyanins composition of B. heteropoda Schrenk and for further utilising them as a promising anthocyanin pigment source. This research enriched the chemical information of B. heteropoda Schrenk. Full article
(This article belongs to the Special Issue Anthocyanins) Printed Edition available
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Open AccessArticle Aroma-Active Compounds in Jinhua Ham Produced With Different Fermentation Periods
Molecules 2014, 19(11), 19097-19113; doi:10.3390/molecules191119097
Received: 12 September 2014 / Revised: 21 October 2014 / Accepted: 5 November 2014 / Published: 19 November 2014
Cited by 3 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text
Abstract
The aroma-active compounds in Jinhua ham processed and stored for 9, 12, 15 and 18 months were extracted by dynamic headspace sampling (DHS) and solvent-assisted flavor evaporation (SAFE) and analyzed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). In GC-O-MS, volatile compounds were identified based on
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The aroma-active compounds in Jinhua ham processed and stored for 9, 12, 15 and 18 months were extracted by dynamic headspace sampling (DHS) and solvent-assisted flavor evaporation (SAFE) and analyzed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). In GC-O-MS, volatile compounds were identified based on their mass spectrum, linear retention index (LRI), odor properties, or reference compound comparisons. The results showed that a total number of 81 aroma-active compounds were identified by GC-O-MS. Among them, acids (such as acetic acid, butanoic acid and 3-methylbutanoic acid), saturated aldehydes (such as hexanal, heptanal, octanal and 3-methylbutanal), benzene derivatives (such as benzeneacetic acid), ester and lactone (such as γ-nonalactone and γ-decalactone) were identified as critical compounds in Jinhua ham aroma. The results also indicated that the type and content of the odorants increased significantly with the duration of the fermentation period. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Vernonia kotschyana Roots: Therapeutic Potential via Antioxidant Activity
Molecules 2014, 19(11), 19114-19136; doi:10.3390/molecules191119114
Received: 10 August 2014 / Revised: 12 November 2014 / Accepted: 12 November 2014 / Published: 19 November 2014
Cited by 2 | PDF Full-text (345 KB) | HTML Full-text | XML Full-text
Abstract
The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts
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The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts for their in vitro antioxidant activity and phenolic content. The roots were extracted successively with chloroform, ethyl acetate, ethanol and water. The antioxidant activity of root extracts was evaluated in both cell-free and cell-based assays. Their chemical characterization was performed by Fourier transform infrared spectroscopy (FT-IR) whereas the total phenolic content was determined by the Folin-Ciocalteu method. The ethyl acetate extract displayed the highest phenolic content and was found to be the most active in the free radical scavenging and lipid peroxidation inhibition assays; it also showed a high antioxidant activity in MCF-12F cells. This study suggests a potential use of the ethyl acetate extract of Vernonia kotschyana not only as an antioxidant agent in gastroduodenal ulcers and gastritis, but also in other disorders characterized by high levels of oxidative stress. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Spectral and Kinetic Properties of Radicals Derived from Oxidation of Quinoxalin-2-One and Its Methyl Derivative
Molecules 2014, 19(11), 19152-19171; doi:10.3390/molecules191119152
Received: 9 October 2014 / Revised: 12 November 2014 / Accepted: 13 November 2014 / Published: 19 November 2014
Cited by 3 | PDF Full-text (1756 KB) | HTML Full-text | XML Full-text
Abstract
The kinetics and spectral characteristics of the transients formed in the reactions of OH and N3 with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at
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The kinetics and spectral characteristics of the transients formed in the reactions of OH and N3 with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at pH 7. The transient absorption spectra recorded in the reactions of OH with Q and 3-MeQ consisted of an absorption band with λmax = 470 nm assigned to the OH-adducts on the benzene ring, and a second band with λmax = 390 nm (for Q) and 370 nm (for 3-MeQ) assigned, inter alia, to the N-centered radicals on a pyrazin-2-one ring. The rate constants of the reactions of OH with Q and 3-MeQ were found to be in the interval (5.9–9.7) × 109 M–1·s–1 and were assigned to their addition to benzene and pyrazin-2-one rings and H-abstraction from the pyrazin-2-one nitrogen. In turn, the transient absorption spectrum observed in the reaction of N3 exhibits an absorption band with λmax = 350 nm. This absorption was assigned to the N-centered radical on the Pyr ring formed after deprotonation of the respective radical cation resulting from one-electron oxidation of 3-MeQ. The rate constant of the reaction of N3 with 3 MeQ was found to be (6.0 ± 0.5) × 109 M–1·s–1. Oxidation of 3-MeQ by N3 and Pyr by OH and N3 confirms earlier spectral assignments. With the rate constant of the OH radical with Pyr (k = 9.2 ± 0.2) × 109 M–1·s‒1, a primary distribution of the OH attack was estimated nearly equal between benzene and pyrazin-2-one rings. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle Anti-Cholinesterase Activity of Lycopodium Alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis
Molecules 2014, 19(11), 19172-19179; doi:10.3390/molecules191119172
Received: 6 October 2014 / Revised: 14 November 2014 / Accepted: 17 November 2014 / Published: 19 November 2014
Cited by 3 | PDF Full-text (456 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa.
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A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. Among them, lycosquarosine A (1) is the new metabolite of the natural source. Lycosquarosine A completely inhibited AChE activity in a dose dependent manner with an IC50 value of 54.3 μg/mL, while acetylaposerratinine (2) showed stronger inhibitory activity than 1 with an IC50 value of 15.2 µg/mL. This result indicates that these alkaloids may be a potent source of AChE inhibitors. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Discovery of Novel Small-Molecule Compounds with Selective Cytotoxicity for Burkitt’s Lymphoma Cells Using 3D Ligand-Based Virtual Screening
Molecules 2014, 19(11), 19209-19219; doi:10.3390/molecules191119209
Received: 15 October 2014 / Revised: 6 November 2014 / Accepted: 11 November 2014 / Published: 19 November 2014
PDF Full-text (1822 KB) | HTML Full-text | XML Full-text
Abstract
We describe a ligand-based approach towards compounds with more specific targeting for Burkitt’s lymphoma. Using three-dimensional ligand-based similarity searches and a previously described hit compound, we have identified six compounds that are chemically different but with similar spatial conformations. Biological evaluation revealed that
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We describe a ligand-based approach towards compounds with more specific targeting for Burkitt’s lymphoma. Using three-dimensional ligand-based similarity searches and a previously described hit compound, we have identified six compounds that are chemically different but with similar spatial conformations. Biological evaluation revealed that one compound has better growth inhibition and improved selectivity towards Burkitt’s lymphoma cells than the query compound. However, initial mechanism-of-action studies show a different target profile in comparison with the previous hit compound, which does not involve the inhibition of the proteasome or the NFκB pathway. The data from this study provide a solid basis for further efforts in the search for selective agents against Burkitt’s lymphoma. Full article
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Open AccessArticle Volatile Profiling of Aromatic Traditional Medicinal Plant, Polygonum minus in Different Tissues and Its Biological Activities
Molecules 2014, 19(11), 19220-19242; doi:10.3390/molecules191119220
Received: 22 August 2014 / Revised: 10 November 2014 / Accepted: 11 November 2014 / Published: 20 November 2014
Cited by 9 | PDF Full-text (615 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots) of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME) and
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The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots) of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME) and hydrodistillation coupled with Gas Chromatography-Mass Spectrometry (GC-MS). Approximately, 77 metabolites have been identified and aliphatic compounds contribute significantly towards the aroma and flavour of this plant. Two main aliphatic compounds: decanal and dodecanal were found to be the major contributor. Terpenoid metabolites were identified abundantly in leaves but not in the stem and root of this plant. Further studies on antioxidant, total phenolic content, anticholinesterase and antimicrobial activities were determined in the essential oil and five different extracts. The plant showed the highest DPPH radical scavenging activity in polar (ethanol) extract for all the tissues tested. For anti-acetylcholinesterase activity, leaf in aqueous extract and methanol extract showed the best acetylcholinesterase inhibitory activities. However, in microbial activity, the non-polar extracts (n-hexane) showed high antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA) compared to polar extracts. This study could provide the first step in the phytochemical profiles of volatile compounds and explore the additional value of pharmacology properties of this essential oil producing crop Polygonum minus. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Antifungal Compounds Produced by Colletotrichum gloeosporioides, an Endophytic Fungus from Michelia champaca
Molecules 2014, 19(11), 19243-19252; doi:10.3390/molecules191119243
Received: 8 October 2014 / Revised: 14 November 2014 / Accepted: 14 November 2014 / Published: 21 November 2014
Cited by 8 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated
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In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated phytopathogenic fungi. Chemical investigation of EtOAc extracts of the endophytic fungus Colletotrichum gloeosporioides resulted in the isolation of one new compound, 2-phenylethyl 1H-indol-3-yl-acetate (1), and seven known compounds: uracil (2), cyclo-(S*-Pro-S*-Tyr) (3), cyclo-(S*-Pro-S*-Val) (4), 2(2-aminophenyl)acetic acid (5), 2(4-hydroxyphenyl)acetic acid (6), 4-hydroxy- benzamide (7) and 2(2-hydroxyphenyl)acetic acid (8). All of the compound structures were elucidated using 1D and 2D NMR and MS analyses. The antifungal and AChE inhibitory activities of compounds 18 were evaluated in vitro. Compound 1 exhibited promising activity against Cladosporium cladosporioides and C. sphaerospermum that was comparable to that of the positive control nystatin. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Compared Binding Properties between Resveratrol and Other Polyphenols to Plasmatic Albumin: Consequences for the Health Protecting Effect of Dietary Plant Microcomponents
Molecules 2014, 19(11), 17066-17077; doi:10.3390/molecules191117066
Received: 30 August 2014 / Revised: 7 October 2014 / Accepted: 9 October 2014 / Published: 24 October 2014
Cited by 15 | PDF Full-text (441 KB) | HTML Full-text | XML Full-text
Abstract
Phytophenols are considered to have beneficial effects towards human physiology. They are food microcomponents with potent chemopreventive properties towards the most three frequent contemporary human diseases, e.g., cardiovascular alterations, cancer and neurodegenerative pathologies. Related to this, the plasmatic form and plasmatic level of
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Phytophenols are considered to have beneficial effects towards human physiology. They are food microcomponents with potent chemopreventive properties towards the most three frequent contemporary human diseases, e.g., cardiovascular alterations, cancer and neurodegenerative pathologies. Related to this, the plasmatic form and plasmatic level of plant polyphenols in the body circulation are crucial for their efficiency. Thus, determinations of the binding process of resveratrol and of common flavonoids produced by major edible plants, berries and fruits to plasma proteins are essential. The interactions between resveratrol and albumin, a major plasma protein, were compared with those already published, involving curcumin, genistein, quercetin and other well-known food-containing polyphenols. The approaches used are usually intrinsic fluorescence intensity changes, quenching of protein intrinsic fluorescence and infrared spectroscopy. It appears that: (1) all of the studied polyphenols interact with albumin; (2) while most of the studied polyphenols interact at one albumin binding site, there are two different types of resveratrol binding sites for bovine serum albumin, one with the highest affinity (apparent KD of 4 µM) with a stoichiometry of one per monomer and a second with a lower affinity (apparent KD of 20 µM) with also a stoichiometry of one per monomer; (3) at least one binding site is in the vicinity of one tryptophanyl residue of bovine serum albumin; and (4) resveratrol binding to bovine serum albumin produces a very small structural conformation change of the polypeptide chain. These results support a role played by polyphenols-albumin interactions in the plasma for the bio-activities of these food microcomponents in the body. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Endocannabinoids, Related Compounds and Their Metabolic Routes
Molecules 2014, 19(11), 17078-17106; doi:10.3390/molecules191117078
Received: 1 August 2014 / Revised: 16 October 2014 / Accepted: 16 October 2014 / Published: 24 October 2014
Cited by 40 | PDF Full-text (1727 KB) | HTML Full-text | XML Full-text
Abstract
Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacological effects of the Δ9-tetrahydrocannabinol. These bioactive lipids belong mainly to two classes of compounds: N-acylethanolamines and acylesters, being N-arachidonoylethanolamine
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Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacological effects of the Δ9-tetrahydrocannabinol. These bioactive lipids belong mainly to two classes of compounds: N-acylethanolamines and acylesters, being N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, their main representatives. During the last twenty years, an ever growing number of fatty acid derivatives (endocannabinoids and endocannabinoid-like compounds) have been discovered and their activities biological is the subject of intense investigations. Here, the most recent advances, from a therapeutic point of view, on endocannabinoids, related compounds, and their metabolic routes will be reviewed. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Enhancing the Delivery of Resveratrol in Humans: If Low Bioavailability is the Problem, What is the Solution?
Molecules 2014, 19(11), 17154-17172; doi:10.3390/molecules191117154
Received: 17 September 2014 / Revised: 21 October 2014 / Accepted: 21 October 2014 / Published: 24 October 2014
Cited by 45 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol has emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. The poor bioavailability of resveratrol in humans has been a major concern for translating basic science findings into clinical utility. Although a number
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Resveratrol has emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. The poor bioavailability of resveratrol in humans has been a major concern for translating basic science findings into clinical utility. Although a number of positive findings have emerged from human clinical trials, there remain many conflicting results, which may partially be attributed to the dosing protocols used. A number of theoretical solutions have been developed to improve the bioavailability of resveratrol, including consumption with various foods, micronized powders, combining it with additional phytochemicals, controlled release devices, and nanotechnological formulations. While laboratory models indicate these approaches all have potential to improve bioavailability of resveratrol and optimize its clinical utility, there is surprisingly very little data regarding the bioavailability of resveratrol in humans. If bioavailability is indeed a limitation in the clinical utility of resveratrol, there is a need to further explore methods to optimize bioavailability in humans. This review summarizes the current bioavailability data, focusing on data from humans, and provides suggested directions for future research in this realm. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery
Molecules 2014, 19(11), 17221-17255; doi:10.3390/molecules191117221
Received: 22 August 2014 / Revised: 13 October 2014 / Accepted: 17 October 2014 / Published: 27 October 2014
Cited by 12 | PDF Full-text (1654 KB) | HTML Full-text | XML Full-text
Abstract
How can diversity-oriented strategies for chemical synthesis provide chemical tools to help shape our understanding of complex cancer pathways and progress anti-cancer drug discovery efforts? This review (surveying the literature from 2003 to the present) considers the applications of diversity-oriented synthesis (DOS), biology-oriented
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How can diversity-oriented strategies for chemical synthesis provide chemical tools to help shape our understanding of complex cancer pathways and progress anti-cancer drug discovery efforts? This review (surveying the literature from 2003 to the present) considers the applications of diversity-oriented synthesis (DOS), biology-oriented synthesis (BIOS) and associated strategies to cancer biology and drug discovery, summarising the syntheses of novel and often highly complex scaffolds from pluripotent or synthetically versatile building blocks. We highlight the role of diversity-oriented synthetic strategies in producing new chemical tools to interrogate cancer biology pathways through the assembly of relevant libraries and their application to phenotypic and biochemical screens. The use of diversity-oriented strategies to explore structure-activity relationships in more advanced drug discovery projects is discussed. We show how considering appropriate and variable focus in library design has provided a spectrum of DOS approaches relevant at all stages in anti-cancer drug discovery. Full article
(This article belongs to the Special Issue Recent Advances in Diversity-Oriented Synthesis)
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Open AccessReview Use of Carbon Nanotubes (CNTs) with Polymers in Solar Cells
Molecules 2014, 19(11), 17329-17344; doi:10.3390/molecules191117329
Received: 5 September 2014 / Revised: 30 September 2014 / Accepted: 17 October 2014 / Published: 28 October 2014
Cited by 17 | PDF Full-text (750 KB) | HTML Full-text | XML Full-text
Abstract
There is a clear need to make energy cheap, readily accessible and green, while ensuring its production does not contribute to further climate change. Of all the options available, photovoltaics offer the highest probability of delivering a meaningful and sustainable change in the
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There is a clear need to make energy cheap, readily accessible and green, while ensuring its production does not contribute to further climate change. Of all the options available, photovoltaics offer the highest probability of delivering a meaningful and sustainable change in the way society produces its energy. One approach to the development of such photovoltaics involves the use of polymers. These systems offer the advantages of cheap production, flexibility (and hence a range of deployment opportunities) and tunability of light absorption. However, there are issues with polymer-based photovoltaic systems and one significant effort to improve these systems has involved the use of carbon nanotubes (CNTs). This review will focus on those efforts. CNTs have been used in virtually every component of the devices to help charge conduction, improve electrode flexibility and in some cases as active light absorbing materials. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessReview Advances in Metal-Catalyzed Cross-Coupling Reactions of Halogenated Quinazolinones and Their Quinazoline Derivatives
Molecules 2014, 19(11), 17435-17463; doi:10.3390/molecules191117435
Received: 26 August 2014 / Revised: 10 October 2014 / Accepted: 21 October 2014 / Published: 29 October 2014
Cited by 9 | PDF Full-text (1234 KB) | HTML Full-text | XML Full-text
Abstract
Halogenated quinazolinones and quinazolines are versatile synthetic intermediates for the metal-catalyzed carbon–carbon bond formation reactions such as the Kumada, Stille, Negishi, Sonogashira, Suzuki-Miyaura and Heck cross-coupling reactions or carbon-heteroatom bond formation via the Buchwald-Hartwig cross-coupling to yield novel polysubstituted derivatives. This review presents
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Halogenated quinazolinones and quinazolines are versatile synthetic intermediates for the metal-catalyzed carbon–carbon bond formation reactions such as the Kumada, Stille, Negishi, Sonogashira, Suzuki-Miyaura and Heck cross-coupling reactions or carbon-heteroatom bond formation via the Buchwald-Hartwig cross-coupling to yield novel polysubstituted derivatives. This review presents an overview of the application of these methods on halogenated quinazolin-4-ones and their quinazolines to generate novel polysubstituted derivatives. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessReview A Comprehensive Review of the Structure Elucidation and Biological Activity of Triterpenoids from Ganoderma spp.
Molecules 2014, 19(11), 17478-17535; doi:10.3390/molecules191117478
Received: 11 July 2014 / Revised: 13 August 2014 / Accepted: 15 August 2014 / Published: 30 October 2014
Cited by 26 | PDF Full-text (1637 KB) | HTML Full-text | XML Full-text
Abstract
Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, a traditional Chinese medicine, popularly used for complementary cancer therapy. GTs are lanostane-tetracyclic triterpenes. They have been reported to possess anti-tumor, anti-inflammation, antioxidant, antimicrobial and blood fat reducing effects. To date,
[...] Read more.
Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, a traditional Chinese medicine, popularly used for complementary cancer therapy. GTs are lanostane-tetracyclic triterpenes. They have been reported to possess anti-tumor, anti-inflammation, antioxidant, antimicrobial and blood fat reducing effects. To date, 316 GTs have been found and their similar chemical structures have proved difficult to elucidate. This paper compiles 316 naturally occurring triterpenes from Ganoderma based on the literature published through January 2013 along with their structures, physiological activities and 13C-NMR spectral data. Full article
(This article belongs to the Section Metabolites)
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Open AccessReview Spectrum-Effect Relationships as a Systematic Approach to Traditional Chinese Medicine Research: Current Status and Future Perspectives
Molecules 2014, 19(11), 17897-17925; doi:10.3390/molecules191117897
Received: 5 September 2014 / Revised: 27 October 2014 / Accepted: 29 October 2014 / Published: 4 November 2014
Cited by 13 | PDF Full-text (491 KB) | HTML Full-text | XML Full-text
Abstract
Component fingerprints are a recognized method used worldwide to evaluate the quality of traditional Chinese medicines (TCMs). To foster the strengths and circumvent the weaknesses of the fingerprint technique in TCM, spectrum-effect relationships would complementarily clarify the nature of pharmacodynamic effects in the
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Component fingerprints are a recognized method used worldwide to evaluate the quality of traditional Chinese medicines (TCMs). To foster the strengths and circumvent the weaknesses of the fingerprint technique in TCM, spectrum-effect relationships would complementarily clarify the nature of pharmacodynamic effects in the practice of TCM. The application of the spectrum-effect relationship method is crucial for understanding and interpreting TCM development, especially in the view of the trends towards TCM modernization and standardization. The basic requirement for using this method is in-depth knowledge of the active material basis and mechanisms of action. It is a novel and effective approach to study TCMs and great progress has been made, but to make it more accurate for TCM research purposes, more efforts are needed. In this review, the authors summarize the current knowledge about the spectrum-effect relationship method, including the fingerprint methods, pharmacodynamics studies and the methods of establishing relationships between the fingerprints and pharmacodynamics. Some speculation regarding future perspectives for spectrum-effect relationship approaches in TCM modernization and standardization are also proposed. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Deciphering the Role of Phytoalexins in Plant-Microorganism Interactions and Human Health
Molecules 2014, 19(11), 18033-18056; doi:10.3390/molecules191118033
Received: 17 September 2014 / Revised: 29 October 2014 / Accepted: 29 October 2014 / Published: 5 November 2014
Cited by 36 | PDF Full-text (304 KB) | HTML Full-text | XML Full-text
Abstract
Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In this review we present the
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Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In this review we present the key features of this diverse group of molecules, namely their chemical structures, biosynthesis, regulatory mechanisms, biological activities, metabolism and molecular engineering. Full article
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Open AccessReview Coupled Microwave/Photoassisted Methods for Environmental Remediation
Molecules 2014, 19(11), 18102-18128; doi:10.3390/molecules191118102
Received: 31 August 2014 / Revised: 27 October 2014 / Accepted: 27 October 2014 / Published: 5 November 2014
Cited by 7 | PDF Full-text (6146 KB) | HTML Full-text | XML Full-text
Abstract
The microwave-induced acceleration of photocatalytic reactions was discovered serendipitously in the late 1990s. The activity of photocatalysts is enhanced significantly by both microwave radiation and UV light. Particularly relevant, other than as a heat source, was the enigmatic phenomenon of the non-thermal effect(s)
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The microwave-induced acceleration of photocatalytic reactions was discovered serendipitously in the late 1990s. The activity of photocatalysts is enhanced significantly by both microwave radiation and UV light. Particularly relevant, other than as a heat source, was the enigmatic phenomenon of the non-thermal effect(s) of the microwave radiation that facilitated photocatalyzed reactions, as evidenced when examining various model contaminants in aqueous media. Results led to an examination of the possible mechanism(s) of the microwave effect(s). In the present article we contend that the microwaves’ non-thermal effect(s) is an important factor in the enhancement of TiO2-photoassisted reactions involving the decomposition of organic pollutants in model wastewaters by an integrated (coupled) microwave-/UV-illumination method (UV/MW). Moreover, such coupling of no less than two irradiation methods led to the fabrication and ultimate investigation of microwave discharged electrodeless lamps (MDELs) as optimal light sources; their use is also described. The review focuses on the enhanced activity of photocatalytic reactions when subjected to microwave radiation and concentrates on the authors’ research of the past few years. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessReview UV-Absorption—The Primary Process in Photocatalysis and Some Practical Consequences
Molecules 2014, 19(11), 18192-18214; doi:10.3390/molecules191118192
Received: 27 August 2014 / Revised: 20 October 2014 / Accepted: 23 October 2014 / Published: 6 November 2014
Cited by 14 | PDF Full-text (1342 KB) | HTML Full-text | XML Full-text
Abstract
TiO2 photochemistry studies generally address reactions of photogenerated charge-carriers at the oxide surface or the recombination reactions which control the proportion of charge carriers that reach the surface. By contrast, this review focuses on UV absorption, the first photochemical step in semiconductor
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TiO2 photochemistry studies generally address reactions of photogenerated charge-carriers at the oxide surface or the recombination reactions which control the proportion of charge carriers that reach the surface. By contrast, this review focuses on UV absorption, the first photochemical step in semiconductor photocatalysis. The influence of particle size on absorption and scattering of light by small TiO2 particles is summarized and the importance of considering, the particle size in the application, not the BET or X-ray line broadening size, is emphasized. Three different consequences of UV absorption are then considered. First, two commercially important systems, pigmented polymer films and paints, are used to show that TiO2 can protect from direct photochemical degradation. Then the effect of UV absorption on the measured photocatalytic degradation of aqueous solutions of organics is considered for two separate cases. Firstly, the consequences of UV absorption by TiO2 on the generation of hydroxyl radicals from H2O2 are considered in the context of the claimed synergy between H2O2 and TiO2. Secondly, the effect of altered UV absorption, caused by changed effective particle size of the catalyst, is demonstrated for photocatalysis of propan-2-ol oxidation and salicylic acid degradation. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessReview Spectroscopic Investigation of the Mechanism of Photocatalysis
Molecules 2014, 19(11), 18248-18267; doi:10.3390/molecules191118248
Received: 1 September 2014 / Revised: 21 October 2014 / Accepted: 27 October 2014 / Published: 7 November 2014
Cited by 12 | PDF Full-text (3081 KB) | HTML Full-text | XML Full-text
Abstract
Reaction mechanisms of various kinds of photocatalysts have been reviewed based on the recent reports, in which various spectroscopic techniques including luminol chemiluminescence photometry, fluorescence probe method, electron spin resonance (ESR), and nuclear magnetic resonance (NMR) spectroscopy were applied. The reaction mechanisms elucidated
[...] Read more.
Reaction mechanisms of various kinds of photocatalysts have been reviewed based on the recent reports, in which various spectroscopic techniques including luminol chemiluminescence photometry, fluorescence probe method, electron spin resonance (ESR), and nuclear magnetic resonance (NMR) spectroscopy were applied. The reaction mechanisms elucidated for bare and modified TiO2 were described individually. The modified visible light responsive TiO2 photocatalysts, i.e., Fe(III)-deposited metal-doped TiO2 and platinum complex-deposited TiO2, were studied by detecting paramagnetic species with ESR, •O2 (or H2O2) with chemiluminescence photometry, and OH radicals with a fluorescence probe method. For bare TiO2, the difference in the oxidation mechanism for the different crystalline form was investigated by the fluorescence probe method, while the adsorption and decomposition behaviors of several amino acids and peptides were investigated by 1H-NMR spectroscopy. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessReview Chitin and Chitosan Nanofibers: Preparation and Chemical Modifications
Molecules 2014, 19(11), 18367-18380; doi:10.3390/molecules191118367
Received: 18 September 2014 / Revised: 15 October 2014 / Accepted: 4 November 2014 / Published: 11 November 2014
Cited by 35 | PDF Full-text (1819 KB) | HTML Full-text | XML Full-text
Abstract
Chitin nanofibers are prepared from the exoskeletons of crabs and prawns, squid pens and mushrooms by a simple mechanical treatment after a series of purification steps. The nanofibers have fine nanofiber networks with a uniform width of approximately 10 nm. The method used
[...] Read more.
Chitin nanofibers are prepared from the exoskeletons of crabs and prawns, squid pens and mushrooms by a simple mechanical treatment after a series of purification steps. The nanofibers have fine nanofiber networks with a uniform width of approximately 10 nm. The method used for chitin-nanofiber isolation is also successfully applied to the cell walls of mushrooms. Commercial chitin and chitosan powders are also easily converted into nanofibers by mechanical treatment, since these powders consist of nanofiber aggregates. Grinders and high-pressure waterjet systems are effective for disintegrating chitin into nanofibers. Acidic conditions are the key factor to facilitate mechanical fibrillation. Surface modification is an effective way to change the surface property and to endow nanofiber surface with other properties. Several modifications to the chitin NF surface are achieved, including acetylation, deacetylation, phthaloylation, naphthaloylation, maleylation, chlorination, TEMPO-mediated oxidation, and graft polymerization. Those derivatives and their properties are characterized. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
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Open AccessReview Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms
Molecules 2014, 19(11), 18414-18447; doi:10.3390/molecules191118414
Received: 15 August 2014 / Revised: 28 October 2014 / Accepted: 2 November 2014 / Published: 12 November 2014
Cited by 28 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text
Abstract
The cell division cycle 25 (CDC25) phosphatases include CDC25A, CDC25B and CDC25C. These three molecules are important regulators of several steps in the cell cycle, including the activation of various cyclin-dependent kinases (CDKs). CDC25s seem to have a role in the development of
[...] Read more.
The cell division cycle 25 (CDC25) phosphatases include CDC25A, CDC25B and CDC25C. These three molecules are important regulators of several steps in the cell cycle, including the activation of various cyclin-dependent kinases (CDKs). CDC25s seem to have a role in the development of several human malignancies, including acute myeloid leukemia (AML); and CDC25 inhibition is therefore considered as a possible anticancer strategy. Firstly, upregulation of CDC25A can enhance cell proliferation and the expression seems to be controlled through PI3K-Akt-mTOR signaling, a pathway possibly mediating chemoresistance in human AML. Loss of CDC25A is also important for the cell cycle arrest caused by differentiation induction of malignant hematopoietic cells. Secondly, high CDC25B expression is associated with resistance against the antiproliferative effect of PI3K-Akt-mTOR inhibitors in primary human AML cells, and inhibition of this isoform seems to reduce AML cell line proliferation through effects on NFκB and p300. Finally, CDC25C seems important for the phenotype of AML cells at least for a subset of patients. Many of the identified CDC25 inhibitors show cross-reactivity among the three CDC25 isoforms. Thus, by using such cross-reactive inhibitors it may become possible to inhibit several molecular events in the regulation of cell cycle progression and even cytoplasmic signaling, including activation of several CDKs, through the use of a single drug. Such combined strategies will probably be an advantage in human cancer treatment. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Open AccessReview Resveratrol: Anti-Obesity Mechanisms of Action
Molecules 2014, 19(11), 18632-18655; doi:10.3390/molecules191118632
Received: 9 September 2014 / Revised: 28 October 2014 / Accepted: 10 November 2014 / Published: 14 November 2014
Cited by 47 | PDF Full-text (1380 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the
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Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPα and PPARγ in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by β-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview The Role of Acyl-Glucose in Anthocyanin Modifications
Molecules 2014, 19(11), 18747-18766; doi:10.3390/molecules191118747
Received: 8 October 2014 / Revised: 6 November 2014 / Accepted: 10 November 2014 / Published: 14 November 2014
Cited by 6 | PDF Full-text (594 KB) | HTML Full-text | XML Full-text
Abstract
Higher plants can produce a wide variety of anthocyanin molecules through modification of the six common anthocyanin aglycons that they present. Thus, hydrophilic anthocyanin molecules can be formed and stabilized by glycosylation and acylation. Two types of glycosyltransferase (GT) and acyltransferase (AT) have
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Higher plants can produce a wide variety of anthocyanin molecules through modification of the six common anthocyanin aglycons that they present. Thus, hydrophilic anthocyanin molecules can be formed and stabilized by glycosylation and acylation. Two types of glycosyltransferase (GT) and acyltransferase (AT) have been identified, namely cytoplasmic GT and AT and vacuolar GT and AT. Cytoplasmic GT and AT utilize UDP-sugar and acyl-CoA as donor molecules, respectively, whereas both vacuolar GT and AT use acyl-glucoses as donor molecules. In carnation plants, vacuolar GT uses aromatic acyl-glucoses as the glucose donor in vivo; independently, vacuolar AT uses malylglucose, an aliphatic acyl-glucose, as the acyl-donor. In delphinium and Arabidopsis, p-hydroxybenzoylglucose and sinapoylglucose are used in vivo as bi-functional donor molecules by vacuolar GT and AT, respectively. The evolution of these enzymes has allowed delphinium and Arabidopsis to utilize unique donor molecules for production of highly modified anthocyanins. Full article
(This article belongs to the Special Issue Anthocyanins) Printed Edition available
Open AccessReview Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases
Molecules 2014, 19(11), 18781-18816; doi:10.3390/molecules191118781
Received: 6 October 2014 / Revised: 7 November 2014 / Accepted: 7 November 2014 / Published: 17 November 2014
Cited by 20 | PDF Full-text (734 KB) | HTML Full-text | XML Full-text
Abstract
Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds
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Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Banana Lectin: A Brief Review
Molecules 2014, 19(11), 18817-18827; doi:10.3390/molecules191118817
Received: 9 October 2014 / Revised: 5 November 2014 / Accepted: 12 November 2014 / Published: 17 November 2014
Cited by 7 | PDF Full-text (254 KB) | HTML Full-text | XML Full-text
Abstract
Lectins are a group of proteins of non-immune origin that recognize and bind to carbohydrates without modifying them. Banana is the common name for both herbaceous plants of the genus Musa and for the fruit they produce. They are indeed a promising source
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Lectins are a group of proteins of non-immune origin that recognize and bind to carbohydrates without modifying them. Banana is the common name for both herbaceous plants of the genus Musa and for the fruit they produce. They are indeed a promising source for many medicinal applications. Banana lectins have the potential for inhibiting HIV-1 reverse transcriptase activity, suppressing cancer cell proliferation and stimulating macrophage activities. Nevertheless, compared to other plant lectins, there is relatively little information in the literature on banana lectins, particularly with respect to their structure and biological functions. Herein we focus our review on the structure, functions and exploitable properties of banana lectins. Full article
(This article belongs to the Special Issue Lectins)
Open AccessReview A Review of Recent Research Progress on the Astragalus Genus
Molecules 2014, 19(11), 18850-18880; doi:10.3390/molecules191118850
Received: 22 July 2014 / Revised: 23 October 2014 / Accepted: 24 October 2014 / Published: 17 November 2014
Cited by 26 | PDF Full-text (1430 KB) | HTML Full-text | XML Full-text
Abstract
Astragalus L., is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. and its processed products are listed in the China Pharmacopeia for “qi deficiency” syndrome
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Astragalus L., is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. and its processed products are listed in the China Pharmacopeia for “qi deficiency” syndrome treatment. However, more and more researches on other species of Astragalus have been conducted recently. We summarize the recent researches of Astragalus species in phytochemistry and pharmacology. More than 200 constituents, including saponins and flavonoids, obtained from 46 species of Astragalus genus were collected for this article. In pharmacological studies, crude extracts of Astragalus, as well as isolated constituents showed anti-inflammatory, immunostimulant, antioxidative, anti-cancer, antidiabetic, cardioprotective, hepatoprotective, and antiviral activities. The goal of this article is to provide an overview of chemical and pharmacological studies on the Astragalus species over the last 10 years, which could be of value to new drug or food supplement research and development. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Synthetic Applications of Intramolecular Thiol-Ene “Click” Reactions
Molecules 2014, 19(11), 19137-19151; doi:10.3390/molecules191119137
Received: 17 October 2014 / Revised: 13 November 2014 / Accepted: 14 November 2014 / Published: 19 November 2014
Cited by 17 | PDF Full-text (864 KB) | HTML Full-text | XML Full-text
Abstract
The intermolecular thiol-ene reaction is emerging as a highly efficient; free-radical mediated “click” process with diverse applications in biofunctionalisation and materials science. The related intramolecular thiol-ene reactions offer significant potential for the preparation of a wide range of sulphur containing heterocycles including synthetic
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The intermolecular thiol-ene reaction is emerging as a highly efficient; free-radical mediated “click” process with diverse applications in biofunctionalisation and materials science. The related intramolecular thiol-ene reactions offer significant potential for the preparation of a wide range of sulphur containing heterocycles including synthetic therapeutics such as cyclic peptides and thiosugars. Herein, we review recent advances in intramolecular thiyl-radical mediated reactions and their applications for synthetic and medicinal chemistry. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessReview Antioxidant Property of Coffee Components: Assessment of Methods that Define Mechanisms of Action
Molecules 2014, 19(11), 19180-19208; doi:10.3390/molecules191119180
Received: 6 September 2014 / Revised: 4 November 2014 / Accepted: 4 November 2014 / Published: 19 November 2014
Cited by 29 | PDF Full-text (677 KB) | HTML Full-text | XML Full-text
Abstract
Coffee is a rich source of dietary antioxidants, and this property, coupled with the fact that coffee is one of the world’s most popular beverages, has led to the understanding that coffee is a major contributor to dietary antioxidant intake. Brewed coffee is
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Coffee is a rich source of dietary antioxidants, and this property, coupled with the fact that coffee is one of the world’s most popular beverages, has led to the understanding that coffee is a major contributor to dietary antioxidant intake. Brewed coffee is a complex food matrix with numerous phytochemical components that have antioxidant activity capable of scavenging free radicals, donating hydrogen and electrons, providing reducing activity and also acting as metal ion pro-oxidant chelators. More recent studies have shown that coffee components can trigger tissue antioxidant gene expression and protect against gastrointestinal oxidative stress. This paper will describe different in vitro, cell-free and cell-based assays that both characterize and compare the antioxidant capacity and mechanism of action of coffee and its bioactive constituents. Moreover, evidence of cellular antioxidant activity and correlated specific genomic events induced by coffee components, which are relevant to antioxidant function in both animal and human studies, will be discussed. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessCorrection Correction: Noguerol-Pato, R., et al. Effect on the Aroma Profile of Graciano and Tempranillo Red Wines of the Application of Two Antifungal Treatments onto Vines. Molecules 2014, 19, 12173-12193
Molecules 2014, 19(11), 17422-17423; doi:10.3390/molecules191117422
Received: 16 October 2014 / Accepted: 20 October 2014 / Published: 29 October 2014
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Abstract
The authors wish to make the following correction to paper [1], doi:10.3390/molecules190812173, website: http://www.mdpi.com/1420-3049/19/8/12173.[...] Full article
(This article belongs to the Section Metabolites)
Open AccessCorrection Correction: Three New Ursane-type Triterpenoids from the Stems of Saprosma merrillii. Molecules 2013, 18, 14496-14504
Molecules 2014, 19(11), 18618-18619; doi:10.3390/molecules191118618
Received: 4 October 2014 / Accepted: 5 October 2014 / Published: 13 November 2014
Cited by 3 | PDF Full-text (473 KB) | HTML Full-text | XML Full-text
Abstract
The authors wish to inform readers that there are several minor errors and omissions in the chemical structures of compounds 13 shown in Figure 1 of this paper [1]. Their structures were re-elucidated by detailed analysis of the NMR, MS, and
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The authors wish to inform readers that there are several minor errors and omissions in the chemical structures of compounds 13 shown in Figure 1 of this paper [1]. Their structures were re-elucidated by detailed analysis of the NMR, MS, and X-ray crystallographic data. The E-ring of 13 is a five-membered ring, and the hydroxyls of 3 at C-6 and C-7 are both in a β-orientation rather than α. The corrected Figure 1 is shown below.[...] Full article
(This article belongs to the Section Natural Products)
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