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Molecules, Volume 20, Issue 4 (April 2015), Pages 5260-7437

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Open AccessReview Phytomelatonin: Assisting Plants to Survive and Thrive
Molecules 2015, 20(4), 7396-7437; https://doi.org/10.3390/molecules20047396
Received: 25 February 2015 / Revised: 27 March 2015 / Accepted: 27 March 2015 / Published: 22 April 2015
Cited by 107 | PDF Full-text (2355 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots
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This review summarizes the advances that have been made in terms of the identified functions of melatonin in plants. Melatonin is an endogenously-produced molecule in all plant species that have been investigated. Its concentration in plant organs varies in different tissues, e.g., roots versus leaves, and with their developmental stage. As in animals, the pathway of melatonin synthesis in plants utilizes tryptophan as an essential precursor molecule. Melatonin synthesis is inducible in plants when they are exposed to abiotic stresses (extremes of temperature, toxins, increased soil salinity, drought, etc.) as well as to biotic stresses (fungal infection). Melatonin aids plants in terms of root growth, leaf morphology, chlorophyll preservation and fruit development. There is also evidence that exogenously-applied melatonin improves seed germination, plant growth and crop yield and its application to plant products post-harvest shows that melatonin advances fruit ripening and may improve food quality. Since melatonin was only discovered in plants two decades ago, there is still a great deal to learn about the functional significance of melatonin in plants. It is the hope of the authors that the current review will serve as a stimulus for scientists to join the endeavor of clarifying the function of this phylogenetically-ancient molecule in plants and particularly in reference to the mechanisms by which melatonin mediates its multiple actions. Full article
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Open AccessArticle Copper(I) Complexes of Mesoionic Carbene: Structural Characterization and Catalytic Hydrosilylation Reactions
Molecules 2015, 20(4), 7379-7395; https://doi.org/10.3390/molecules20047379
Received: 24 February 2015 / Revised: 20 March 2015 / Accepted: 23 March 2015 / Published: 22 April 2015
Cited by 9 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two series of different Cu(I)-complexes of “click” derived mesoionic carbenes are reported. Halide complexes of the type (MIC)CuI (with MIC = 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (for 1b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (for 1c)) and cationic complexes of the general formula [Cu(MIC)2]X (with MIC =1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X
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Two series of different Cu(I)-complexes of “click” derived mesoionic carbenes are reported. Halide complexes of the type (MIC)CuI (with MIC = 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (for 1b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (for 1c)) and cationic complexes of the general formula [Cu(MIC)2]X (with MIC =1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X = CuI2 (for ), 1,4-dimesityl-3-methyl-1,2,3-triazol-5-ylidene, X = BF4 (for 2a), 1,4-(2,6-diisopropyl)phenyl-3-methyl-1,2,3-triazol-5-ylidene, X = BF4 (for 2b), 1-benzyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene, X = BF4 (for 2c)) have been prepared from CuI or [Cu(CH3CN)4](BF4) and the corresponding ligands, respectively. All complexes were characterized by elemental analysis and standard spectroscopic methods. Complexes 2á and 1b were studied by single-crystal X-ray diffraction analysis. Structural analysis revealed 2á to adopt a cationic form as [Cu(MIC)2](CuI2) and comparison of the NMR spectra of 2á and 2a confirmed this conformation in solution. In contrast, after crystallization complex 1b was found to adopt the desired neutral form. All complexes were tested for the reduction of cyclohexanone under hydrosilylation condition at elevated temperatures. These complexes were found to be efficient catalysts for this reaction. 2c was also found to catalyze this reaction at room temperature. Mechanistic studies have been carried out as well. Full article
(This article belongs to the collection Advances in Click Chemistry)
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Open AccessArticle Investigation of a Quantitative Method for the Analysis of Chiral Monoterpenes in White Wine by HS-SPME-MDGC-MS of Different Wine Matrices
Molecules 2015, 20(4), 7359-7378; https://doi.org/10.3390/molecules20047359
Received: 16 March 2015 / Revised: 16 April 2015 / Accepted: 16 April 2015 / Published: 22 April 2015
Cited by 6 | PDF Full-text (829 KB) | HTML Full-text | XML Full-text
Abstract
A valid quantitative method for the analysis of chiral monoterpenes in white wine using head-space solid phase micro-extraction-MDGC-MS (HS-SPME-MDGC-MS) with stable isotope dilution analysis was established. Fifteen compounds: (S)-(−)-limonene, (R)-(+)-limonene, (+)-(2R,4S)-cis-rose oxide, (−)-(2S,4R)-cis-rose oxide, (−)-(2R,4R)-trans-rose oxide, (+)-(2S,4S)-
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A valid quantitative method for the analysis of chiral monoterpenes in white wine using head-space solid phase micro-extraction-MDGC-MS (HS-SPME-MDGC-MS) with stable isotope dilution analysis was established. Fifteen compounds: (S)-(−)-limonene, (R)-(+)-limonene, (+)-(2R,4S)-cis-rose oxide, (−)-(2S,4R)-cis-rose oxide, (−)-(2R,4R)-trans-rose oxide, (+)-(2S,4S)-cis-rose oxide, furanoid (+)-trans-linalool oxide, furanoid (−)-cis-linalool oxide, furanoid (−)-trans-linalool oxide, furanoid (+)-cis-linalool oxide, (−)-linalool, (+)-linalool, (−)-α-terpineol, (+)-α-terpineol and (R)-(+)-β-citronellol were quantified. Two calibration curves were plotted for different wine bases, with varying residual sugar content, and three calibration curves for each wine base were investigated during a single fiber’s lifetime. This was needed as both sugar content and fiber life impacted the quantification of the chiral terpenes. The chiral monoterpene content of six Pinot Gris wines and six Riesling wines was then analyzed using the verified method. ANOVA with Tukey multiple comparisons showed significant differences for each of the detected chiral compounds in all 12 wines. PCA score plots showed a clear separation between the Riesling and Pinot Gris wines. Riesling wines had greater number of chiral terpenes in comparison to Pinot Gris wines. Beyond total terpene content it is possible that the differences in chiral terpene content may be driving the aromatic differences in white wines. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessReview Antibacterial Activity of Essential Oils and Their Isolated Constituents against Cariogenic Bacteria: A Systematic Review
Molecules 2015, 20(4), 7329-7358; https://doi.org/10.3390/molecules20047329
Received: 24 February 2015 / Revised: 4 April 2015 / Accepted: 10 April 2015 / Published: 22 April 2015
Cited by 58 | PDF Full-text (1033 KB) | HTML Full-text | XML Full-text
Abstract
Dental caries remains the most prevalent and costly oral infectious disease worldwide. Several methods have been employed to prevent this biofilm-dependent disease, including the use of essential oils (EOs). In this systematic review, we discuss the antibacterial activity of EOs and their isolated
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Dental caries remains the most prevalent and costly oral infectious disease worldwide. Several methods have been employed to prevent this biofilm-dependent disease, including the use of essential oils (EOs). In this systematic review, we discuss the antibacterial activity of EOs and their isolated constituents in view of a potential applicability in novel dental formulations. Seven databases were systematically searched for clinical trials, in situ, in vivo and in vitro studies addressing the topic published up to date. Most of the knowledge in the literature is based on in vitro studies assessing the effects of EOs on caries-related streptococci (mainly Streptococcus mutans) and lactobacilli, and on a limited number of clinical trials. The most promising species with antibacterial potential against cariogenic bacteria are: Achillea ligustica, Baccharis dracunculifolia, Croton cajucara, Cryptomeria japonica, Coriandrum sativum, Eugenia caryophyllata, Lippia sidoides, Ocimum americanum, and Rosmarinus officinalis. In some cases, the major phytochemical compounds determine the biological properties of EOs. Menthol and eugenol were considered outstanding compounds demonstrating an antibacterial potential. Only L. sidoides mouthwash (1%) has shown clinical antimicrobial effects against oral pathogens thus far. This review suggests avenues for further non-clinical and clinical studies with the most promising EOs and their isolated constituents bioprospected worldwide. Full article
(This article belongs to the Section Metabolites)
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Open AccessCorrection Correction: Yang, C.-H., et al. Immobilization of Brassica oleracea Chlorophyllase 1 (BoCLH1) and Candida rugosa Lipase (CRL) in Magnetic Alginate Beads: An Enzymatic Evaluation in the Corresponding Proteins. Molecules 2014, 19, 11800-11815
Molecules 2015, 20(4), 7325-7328; https://doi.org/10.3390/molecules20047325
Received: 2 April 2015 / Accepted: 2 April 2015 / Published: 21 April 2015
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Abstract
The authors wish to correct Scheme 1, and Figures 1, 4 and 7 in [1] as follows. Scheme 1 should include phytol and fatty acid. [...] Full article
(This article belongs to the Special Issue Bio and Nanomaterials Based on Fe3O4)
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Open AccessArticle Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives
Molecules 2015, 20(4), 7309-7324; https://doi.org/10.3390/molecules20047309
Received: 6 March 2015 / Revised: 15 April 2015 / Accepted: 17 April 2015 / Published: 21 April 2015
Cited by 15 | PDF Full-text (1662 KB) | HTML Full-text | XML Full-text
Abstract
Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were
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Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 410 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 1117 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA. Full article
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Open AccessArticle Evaluation of Novel Antibacterial N-Halamine Nanoparticles Prodrugs towards Susceptibility of Escherichia coli Induced by DksA Protein
Molecules 2015, 20(4), 7292-7308; https://doi.org/10.3390/molecules20047292
Received: 12 March 2015 / Revised: 3 April 2015 / Accepted: 7 April 2015 / Published: 21 April 2015
Cited by 7 | PDF Full-text (3664 KB) | HTML Full-text | XML Full-text
Abstract
Novel N-halamine nanoparticles potentially useful for killing pathogenic bacteria, i.e., SiO2@PS/N-halamine NPs, were successfully synthesized via the immobilization of N-halamines onto the polystyrene-coated silica nanoparticles (SiO2@PS NPs). The effect of reaction conditions, i.e.,
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Novel N-halamine nanoparticles potentially useful for killing pathogenic bacteria, i.e., SiO2@PS/N-halamine NPs, were successfully synthesized via the immobilization of N-halamines onto the polystyrene-coated silica nanoparticles (SiO2@PS NPs). The effect of reaction conditions, i.e., chlorination temperature, bleaching concentration, chlorination time, on the oxidative chlorine content in the products was systematically investigated. The antibacterial activity of the products was tested via the modified plate counting methd using Escherichia coli (E. coli) as a model bacterium. The possible mechanism of the antibacterial action of the products was also studied using scanning electron microscopy combined with a inhibition zone study. The antimicrobial capability of the products was well controlled by tuning the oxidative chlorine content in the products. More importantly, the role of DksA protein in the susceptibility of E. coli against the products was proven using a time-kill assay. This in-depth investigation of the sensitivity of E. coli towards N-halamine NPs provides a systematic understanding of the utility of N-halamines for deactivating bacteria or even disease control. Full article
(This article belongs to the Special Issue Prodrugs)
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Open AccessArticle Photorelease of Pyridyl Esters in Organometallic Ru(II) Arene Complexes
Molecules 2015, 20(4), 7276-7291; https://doi.org/10.3390/molecules20047276
Received: 20 February 2015 / Revised: 14 April 2015 / Accepted: 15 April 2015 / Published: 21 April 2015
Cited by 9 | PDF Full-text (2581 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New Ru(II) arene complexes of formula [(η6-p-cym)Ru(N-N)(X)]2+ (where p-cym = para-cymene, N-N = 2,2'-bipyrimidine (bpm) or 2,2'-bipyridine (bpy) and X = m/p-COOMe-Py, 14) were synthesised and characterized, including the molecular structure
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New Ru(II) arene complexes of formula [(η6-p-cym)Ru(N-N)(X)]2+ (where p-cym = para-cymene, N-N = 2,2'-bipyrimidine (bpm) or 2,2'-bipyridine (bpy) and X = m/p-COOMe-Py, 14) were synthesised and characterized, including the molecular structure of complexes [(η6-p-cym)Ru(bpy)(m-COOMe-Py)]2+ (3) and [(η6-p-cym)Ru(bpy) (p-COOMe-Py)]2+ (4) by single-crystal X-ray diffraction. Complexes 14 are stable in the dark in aqueous solution over 48 h and photolysis studies indicate that they can photodissociate the monodentate m/p-COOMe-Py ligands selectively with yields lower than 1%. DFT and TD-DFT calculations (B3LYP/LanL2DZ/6-31G**) performed on singlet and triplet states pinpoint a low-energy triplet state as the reactive state responsible for the selective dissociation of the monodentate pyridyl ligands. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
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Open AccessArticle Bifunctionalized Allenes. Part XVI. Synthesis of 3-Phosphoryl-2,5-dihydrofurans by Coinage Metal-Catalyzed Cyclo-isomerization of Phosphorylated α-Hydroxyallenes
Molecules 2015, 20(4), 7263-7275; https://doi.org/10.3390/molecules20047263
Received: 23 March 2015 / Revised: 15 April 2015 / Accepted: 17 April 2015 / Published: 21 April 2015
Cited by 7 | PDF Full-text (733 KB) | HTML Full-text | XML Full-text
Abstract
Phosphorylated α-hydroxyallenes 1 and 2 were smoothly converted into the corresponding 2,5-dihydrofurans 3 and 4 in an 5-endo-trig cycloisomerization reaction by using 5 mol % of coinage metal salts as catalyst. Experimental conditions such as the type of the solvent, the reaction
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Phosphorylated α-hydroxyallenes 1 and 2 were smoothly converted into the corresponding 2,5-dihydrofurans 3 and 4 in an 5-endo-trig cycloisomerization reaction by using 5 mol % of coinage metal salts as catalyst. Experimental conditions such as the type of the solvent, the reaction temperature, the mol % and the type of the catalyst were optimized. This mild and efficient cyclization method can be applied to dimethyl 1-hydroxyalkyl-alka-1,2-dienephosphonates 1 and 2-diphenylphosphinoyl-2,3-dien-1-ols 2ac and 3-diphenylphosphinoyl-3,4-dien-2-ols 2d,e, furnishing 3-phosphorylated 2,5-dihydrofurans 3 and 4 in very good yields. Full article
(This article belongs to the Section Organic Chemistry)
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Open AccessArticle Diterpenes Synthesized from the Natural Serrulatane Leubethanol and Their in Vitro Activities against Mycobacterium tuberculosis
Molecules 2015, 20(4), 7245-7262; https://doi.org/10.3390/molecules20047245
Received: 2 February 2015 / Revised: 30 March 2015 / Accepted: 13 April 2015 / Published: 21 April 2015
Cited by 5 | PDF Full-text (805 KB) | HTML Full-text | XML Full-text
Abstract
Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity
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Seventeen new derivatives of the natural diterpene leubethanol, including some potential pro-drugs, with changes in the functionality of the aliphatic chain or modifications of aromatic ring and the phenolic group, were synthesized and tested in vitro by the MABA technique for their activity against the H37Rv strain of Mycobacterium tuberculosis. Some compounds showed antimycobacterial selectivity indices higher than leubethanol. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex
Molecules 2015, 20(4), 7222-7244; https://doi.org/10.3390/molecules20047222
Received: 20 March 2015 / Revised: 14 April 2015 / Accepted: 15 April 2015 / Published: 21 April 2015
Cited by 3 | PDF Full-text (1999 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base.
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The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90 °C using triethylamine as the base. These milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that degrade or react at the normal 140 °C reaction temperature. An analytical protocol for separating the S and R enantiomers of two of the most active compounds is also disclosed. Finally, the X-ray structure for the most active enantiomer of the lead compound, (S)-RAB1, is given. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview Recent Developments of Versatile Photoinitiating Systems for Cationic Ring Opening Polymerization Operating at Any Wavelengths and under Low Light Intensity Sources
Molecules 2015, 20(4), 7201-7221; https://doi.org/10.3390/molecules20047201
Received: 25 February 2015 / Revised: 27 March 2015 / Accepted: 30 March 2015 / Published: 20 April 2015
Cited by 24 | PDF Full-text (2276 KB) | HTML Full-text | XML Full-text
Abstract
Photoinitiators (PI) or photoinitiating systems (PIS) usable in light induced cationic polymerization (CP) and free radical promoted cationic polymerization (FRPCP) reactions (more specifically for cationic ring opening polymerization (ROP)) together with the involved mechanisms are briefly reviewed. The recent developments of novel two-
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Photoinitiators (PI) or photoinitiating systems (PIS) usable in light induced cationic polymerization (CP) and free radical promoted cationic polymerization (FRPCP) reactions (more specifically for cationic ring opening polymerization (ROP)) together with the involved mechanisms are briefly reviewed. The recent developments of novel two- and three-component PISs for CP and FRPCP upon exposure to low intensity blue to red lights is emphasized in details. Examples of such reactions under various experimental conditions are provided. Full article
(This article belongs to the Special Issue Ring-Opening Polymerization)
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Open AccessArticle Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies
Molecules 2015, 20(4), 7174-7200; https://doi.org/10.3390/molecules20047174
Received: 27 February 2015 / Revised: 8 April 2015 / Accepted: 13 April 2015 / Published: 20 April 2015
Cited by 9 | PDF Full-text (3703 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are
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The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p) displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Characterization of a (2R,3R)-2,3-Butanediol Dehydrogenase from Rhodococcus erythropolis WZ010
Molecules 2015, 20(4), 7156-7173; https://doi.org/10.3390/molecules20047156
Received: 12 March 2015 / Revised: 13 April 2015 / Accepted: 14 April 2015 / Published: 20 April 2015
Cited by 9 | PDF Full-text (1915 KB) | HTML Full-text | XML Full-text
Abstract
The gene encoding a (2R,3R)-2,3-butanediol dehydrogenase from Rhodococcus erythropolis WZ010 (ReBDH) was over-expressed in Escherichia coli and the resulting recombinant ReBDH was successfully purified by Ni-affinity chromatography. The purified ReBDH in the native form was found to exist as
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The gene encoding a (2R,3R)-2,3-butanediol dehydrogenase from Rhodococcus erythropolis WZ010 (ReBDH) was over-expressed in Escherichia coli and the resulting recombinant ReBDH was successfully purified by Ni-affinity chromatography. The purified ReBDH in the native form was found to exist as a monomer with a calculated subunit size of 37180, belonging to the family of the zinc-containing alcohol dehydrogenases. The enzyme was NAD(H)-specific and its optimal activity for acetoin reduction was observed at pH 6.5 and 55 °C. The optimal pH and temperature for 2,3-butanediol oxidation were pH 10 and 45 °C, respectively. The enzyme activity was inhibited by ethylenediaminetetraacetic acid (EDTA) or metal ions Al3+, Zn2+, Fe2+, Cu2+ and Ag+, while the addition of 10% (v/v) dimethyl sulfoxide (DMSO) in the reaction mixture increased the activity by 161.2%. Kinetic parameters of the enzyme showed lower Km values and higher catalytic efficiency for diacetyl and NADH in comparison to those for (2R,3R)-2,3-butanediol and NAD+. The activity of acetoin reduction was 7.7 times higher than that of (2R,3R)-2,3-butanediol oxidation when ReBDH was assayed at pH 7.0, suggesting that ReBDH-catalyzed reaction in vivo might favor (2R,3R)-2,3-butanediol formation rather than (2R,3R)-2,3-butanediol oxidation. The enzyme displayed absolute stereospecificity in the reduction of diacetyl to (2R,3R)-2,3-butanediol via (R)-acetoin, demonstrating its potential application on the synthesis of (R)-chiral alcohols. Full article
(This article belongs to the Special Issue Enzyme-Catalyzed Reactions)
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Open AccessArticle Inhibition of Oxidative Stress and Skin Aging-Related Enzymes by Prenylated Chalcones and Other Flavonoids from Helichrysum teretifolium
Molecules 2015, 20(4), 7143-7155; https://doi.org/10.3390/molecules20047143
Received: 8 March 2015 / Revised: 9 April 2015 / Accepted: 14 April 2015 / Published: 20 April 2015
Cited by 14 | PDF Full-text (736 KB) | HTML Full-text | XML Full-text
Abstract
Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone (
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Ten flavonoid-related structures viz. heliteretifolin (1), isoxanthohumol (2), 2',4',6'-trihydroxy-3'-prenylchalcone (3), isoglabranin (4), glabranin (5), 7-methoxy-isoglabranin (6), quercetin (7), 4'-methoxyquercetin (8), 4'-methoxykaempferol (9) and mosloflavone (10) were isolated from a H. teretifolium methanolic extract and identified. One of them (compound 1) is reported for the first time from a natural source, while compounds 6, 810 were isolated for the first time from the genus Helichrysum. The total extract of H. teretifolium showed potent antioxidant activity. When tested for total antioxidant capacity compound 3 possesses moderate biological activity compared to 2, which displayed some of the highest TEAC values (4529.01 ± 2.44; 4170.66 ± 6.72) µM TE/g, respectively. Compounds 7 and 8 demonstrated the highest inhibitory activities on Fe2+-induced lipid peroxidation (IC50 = 2.931; 6.449 µg/mL); tyrosinase (8.092; 27.573) and elastase (43.342; 86.548). Additionally, the total antioxidant capacities measured as FRAP (4816.31 ± 7.42; 3584.17 ± 0.54) µM AAE/g, and ORAC for hydroxyl radical (7.265 ± 0.71; 6.779 ± 3.40) × 106 and peroxyl radical (17.836 ± 2.90; 12.545 ± 5.07) × 103 µM TE/g were also observed for compounds 7 and 8, respectively. In conclusion, H. teretifolium total extract represents a rich source of bioactive constituents with potent antioxidant and moderate anti-tyrosinase and anti-elastase activities that can help to avert accumulation of free radicals in the body, and could therefore be good candidates for the prevention and/or treatment of skin-related conditions, such as aging. This is the first scientific report on the chemical and biological profile of H. teretifolium. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessReview A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2012
Molecules 2015, 20(4), 7097-7142; https://doi.org/10.3390/molecules20047097
Received: 21 January 2015 / Revised: 1 April 2015 / Accepted: 3 April 2015 / Published: 20 April 2015
Cited by 25 | PDF Full-text (1111 KB) | HTML Full-text | XML Full-text
Abstract
Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals,
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Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR) investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity. In 2012, approximately 138 molecules from marine sources, including isolated compounds and their associated analogues, were shown to be promising anticancer drugs. Among these, 62% are novel compounds. In this report, we review the marine compounds identified in 2012 that may serve as novel anticancer drugs. Full article
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Open AccessArticle Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3
Molecules 2015, 20(4), 7059-7096; https://doi.org/10.3390/molecules20047059
Received: 5 March 2015 / Revised: 29 March 2015 / Accepted: 1 April 2015 / Published: 20 April 2015
Cited by 5 | PDF Full-text (2718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers bearing
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Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers bearing mixtures of galactosides, lactosides, and N-acetylgalactosaminosides, galectin-3 ligands, multivalently affect galectin-3 functions. We further demonstrate that lactose functionalized glycodendrimers multivalently bind a different member of the galectin family, i.e., galectin-1. In a modified ELISA, galectin-3 recruitment by glycodendrimers was shown to directly depend on the ratio of low to high affinity ligands on the dendrimers, with lactose-functionalized dendrimers having the highest activity and also binding well to galectin-1. The results depicted here indicate that synthetic multivalent systems and upfront assay formats will improve the understanding of the multivalent function of galectins during multivalent protein carbohydrate recognition/interaction. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
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Open AccessArticle Preparative Isolation and Purification of Lignans from Justicia procumbens Using High-Speed Counter-Current Chromatography in Stepwise Elution Mode
Molecules 2015, 20(4), 7048-7058; https://doi.org/10.3390/molecules20047048
Received: 8 March 2015 / Revised: 3 April 2015 / Accepted: 8 April 2015 / Published: 20 April 2015
Cited by 6 | PDF Full-text (743 KB) | HTML Full-text | XML Full-text
Abstract
Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of four
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Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of four lignans (justicidin B (1), justicidin A (2), 6'-hydroxyjusticidin C (3) and lignan J1 (4)) from J. procumbens using stepwise elution with a pair of two-phase solvent systems composed of n-hexane–ethyl acetate–methanol–water at (1.3:1:1.3:1, v/v) and (2.5:1:2.5:1, v/v). The preparative HSCCC separation was performed on 300 mg of crude sample yielding compounds 1 (19.7 mg), 2 (9.86 mg), 3 (11.26 mg), and 4 (2.54 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these compounds were identified by MS, 1H-NMR and 13C-NMR. This is the first report on the application of HSCCC to the efficient separation of lignans from J. procumbens. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Phytochemical Compositions and Biological Activities of Essential Oil from Xanthium strumarium L.
Molecules 2015, 20(4), 7034-7047; https://doi.org/10.3390/molecules20047034
Received: 5 February 2015 / Revised: 13 April 2015 / Accepted: 14 April 2015 / Published: 17 April 2015
Cited by 31 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices.
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The chemical composition of the essential oil (EO) from fresh cocklebur (Xanthium strumarium L.) leaves was investigated by GC-MS. The antimicrobial activity of the EO was tested against Gram-positive and Gram-negative bacteria and fungi. Scolicidal activity was assayed against Echinococcus granulosus protoscolices. In total, 34 compounds were identified, accounting for 98.96% of the EO. The main compounds in the EO were cis-β-guaiene (34.2%), limonene (20.3%), borneol (11.6%), bornyl acetate (4.5%), β-cubebene (3.8%), sabinene (3.6%), phytol (3.1%), β-selinene (2.8%), camphene (2.2%), α-cubebene (2.4%), β-caryophyllene (1.9%), α-pinene (1.8%) and xanthinin (1.04%). The antibacterial and antifungal screening of the EO showed that all assayed concentrations significantly inhibited the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger (MIC = 0.5 ± 0.1, 1.3 ± 0.0, 4.8 ± 0.0, 20.5 ± 0.3, 55.2 ± 0.0 and 34.3 ± 0.0 µg/mL, respectively). The scolicidal assay indicated that the EO exhibited a significant activity against E. granulosus protoscolices. To the best of our knowledge, this is the first report on the scolicidal activity of X. strumarium. Because of the emergence of antimicrobial drug resistance, the study of new effective natural chemotherapeutic agents, such as the X. strumarium EO, possibly with low side effects, represents a very promising approach in biomedical research. Full article
Open AccessArticle Chilean Prosopis Mesocarp Flour: Phenolic Profiling and Antioxidant Activity
Molecules 2015, 20(4), 7017-7033; https://doi.org/10.3390/molecules20047017
Received: 18 January 2015 / Revised: 9 April 2015 / Accepted: 13 April 2015 / Published: 17 April 2015
Cited by 9 | PDF Full-text (2175 KB) | HTML Full-text | XML Full-text
Abstract
In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples
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In South America, the mesocarp flour of Prosopis species plays a prominent role as a food resource in arid areas. The aim of this work was the characterization of the phenolic antioxidants occurring in the pod mesocarp flour of Chilean Prosopis. Samples were collected in the Copiapo, Huasco and Elqui valleys from the north of Chile. The samples of P. chilensis flour exhibited a total phenolic content ranging between 0.82–2.57 g gallic acid equivalents/100 g fresh flour weight. The highest antioxidant activity, measured by the DPPH assay, was observed for samples from the Huasco valley. HPLC-MS/MS analysis allowed the tentative identification of eight anthocyanins and 13 phenolic compounds including flavonol glycosides, C-glycosyl flavones and ellagic acid derivatives. The antioxidant activity and the phenolic composition in the flour suggest that this ancient South American resource may have potential as a functional food. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessReview Perinatal Asphyxia: A Review from a Metabolomics Perspective
Molecules 2015, 20(4), 7000-7016; https://doi.org/10.3390/molecules20047000
Received: 19 February 2015 / Revised: 1 April 2015 / Accepted: 13 April 2015 / Published: 17 April 2015
Cited by 16 | PDF Full-text (690 KB) | HTML Full-text | XML Full-text
Abstract
Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most
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Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last years, proved to be a useful tool for the monitoring, the assessment, and the identification of potential biomarkers associated with asphyxia events. This review covers metabolomics research on perinatal asphyxia condition, examining in detail the studies reported both on animal and human models. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities
Molecules 2015, 20(4), 6978-6999; https://doi.org/10.3390/molecules20046978
Received: 3 March 2015 / Revised: 8 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
Cited by 3 | PDF Full-text (780 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to
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Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC50 = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Alkylamides of Acmella oleracea
Molecules 2015, 20(4), 6970-6977; https://doi.org/10.3390/molecules20046970
Received: 10 February 2015 / Revised: 25 March 2015 / Accepted: 8 April 2015 / Published: 16 April 2015
Cited by 5 | PDF Full-text (800 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were
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Phytochemical investigation of the flowers of Acmella oleracea had resulted in the isolation of one new alkylamide, (2E,5Z)-N-isobutylundeca-2,5-diene-8,10-diynamide (1), together with four known analogues (2-5). The structures of these compounds were determined by the interpretation of spectroscopic methods, especially NMR technologies (COSY, HSQC, HMBC, and NOESY). In addition, a convenient method for concentrating the alkylamide-rich fraction and analyzing fingerprint profile of A. oleracea was established. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessReview Kinugasa Reactions in Water: From Green Chemistry to Bioorthogonal Labelling
Molecules 2015, 20(4), 6959-6969; https://doi.org/10.3390/molecules20046959
Received: 30 March 2015 / Revised: 12 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
Cited by 14 | PDF Full-text (593 KB) | HTML Full-text | XML Full-text | Correction
Abstract
The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions
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The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy. Full article
(This article belongs to the Special Issue Recent Developments of the Kinugasa Reaction)
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Open AccessArticle NKCS, a Mutant of the NK-2 Peptide, Causes Severe Distortions and Perforations in Bacterial, But Not Human Model Lipid Membranes
Molecules 2015, 20(4), 6941-6958; https://doi.org/10.3390/molecules20046941
Received: 30 January 2015 / Revised: 9 April 2015 / Accepted: 10 April 2015 / Published: 16 April 2015
Cited by 2 | PDF Full-text (3095 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
NKCS is an improved mutant of the bioactive peptide NK-2, which shows strong activity against Escherichia coli and low toxicity towards human cells. The different activity demonstrates the relevance of the physico-chemical nature of the target membrane for the biological effect of this
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NKCS is an improved mutant of the bioactive peptide NK-2, which shows strong activity against Escherichia coli and low toxicity towards human cells. The different activity demonstrates the relevance of the physico-chemical nature of the target membrane for the biological effect of this peptide. We studied the effect of this potent antimicrobial peptide on model membranes by activity studies, differential scanning calorimetry, single molecule tracking and tracer efflux experiments. We found that NKCS severely distorted, penetrated and perforated model lipid membranes that resembled bacterial membranes, but not those that were similar to human cell membranes. The interactions of NKCS with phosphatidylethanolamine, which is abundant in bacterial membranes, were especially strong and are probably responsible for its antimicrobial activity. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides (CPPs))
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Open AccessArticle Identification of the Chemical Constituents in Aqueous Extract of Zhi-Qiao and Evaluation of Its Antidepressant Effect
Molecules 2015, 20(4), 6925-6940; https://doi.org/10.3390/molecules20046925
Received: 30 January 2015 / Revised: 10 April 2015 / Accepted: 14 April 2015 / Published: 16 April 2015
Cited by 16 | PDF Full-text (1250 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ) has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents
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The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ) has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents of ZQ aqueous extract or its anti-depression effects. Firstly, this research reported the on-line identification of the chemical constituents in the aqueous extract of ZQ by coupling ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 31 chemical constituents were identified in ZQ aqueous extract, including one tannic acid, five flavones, 13 flavanones, one limonoid, three coumarins, three cyclic peptides, and five polymethoxylated flavonoids. The antidepressant effect of ZQ aqueous extract was evaluated in vivo and the results indicated that the mice immobility time during the forced swimming test and the tail suspension test were significantly reduced with ZQ treatment. MTT assays showed both ZQ aqueous extract and its major constituents (naringin, hesperidin, neohesperidin, and nobiletin) had neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells. The in vivo and in vitro results suggest that ZQ has an antidepressant effect. Full article
(This article belongs to the Section Natural Products Chemistry)
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Open AccessArticle Accumulation of GD1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V
Molecules 2015, 20(4), 6913-6924; https://doi.org/10.3390/molecules20046913
Received: 14 January 2015 / Revised: 9 April 2015 / Accepted: 14 April 2015 / Published: 16 April 2015
Cited by 8 | PDF Full-text (3807 KB) | HTML Full-text | XML Full-text
Abstract
α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b
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α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer). Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
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Open AccessArticle Simultaneous Quantification of Diazepam and Dexamethasone in Plasma by High-Performance Liquid Chromatography with Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Comparison between Normoxic and Hypoxic Rats
Molecules 2015, 20(4), 6901-6912; https://doi.org/10.3390/molecules20046901
Received: 13 February 2015 / Revised: 7 April 2015 / Accepted: 13 April 2015 / Published: 16 April 2015
Cited by 8 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text
Abstract
In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and
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In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0–100 ng/mL for diazepam and 2.0–200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between −7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Anti-Inflammatory Effect of Wogonin on RAW 264.7 Mouse Macrophages Induced with Polyinosinic-Polycytidylic Acid
Molecules 2015, 20(4), 6888-6900; https://doi.org/10.3390/molecules20046888
Received: 21 February 2015 / Revised: 6 April 2015 / Accepted: 10 April 2015 / Published: 16 April 2015
Cited by 23 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text
Abstract
Wogonin (5,7-dihydroxy-8-methoxyflavone) is an active flavonoid compound originally isolated from Scutellaria radix, which has been used to treat lung inflammation in Korea, China, and Japan. Wogonin has been known to inhibit inducible nitric oxide synthase and have the anti-tumor properties. However, the
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Wogonin (5,7-dihydroxy-8-methoxyflavone) is an active flavonoid compound originally isolated from Scutellaria radix, which has been used to treat lung inflammation in Korea, China, and Japan. Wogonin has been known to inhibit inducible nitric oxide synthase and have the anti-tumor properties. However, the effects of wogonin on virus-induced macrophages are not fully reported. In this study, the anti-inflammatory effect of wogonin on double-stranded RNA (dsRNA)-induced macrophages was examined. Wogonin restored the cell viability in dsRNA [polyinosinic-polycytidylic acid]-induced RAW 264.7 mouse macrophages at concentrations of up to 50 μM. Wogonin significantly inhibited the production of nitric oxide, IL-1α, IL-1β, IL-6, IL-10, IP-10, G-CSF, GM-CSF, LIF (IL-6 class cytokine), LIX/CXCL5, MCP-1, M-CSF, MIP-1α, MIP-1β, MIP-2, RANTES/CCL5, TNF-α, and VEGF as well as calcium release and mRNA expression of signal transducer and activated transcription 1 (STAT1) and STAT3 in dsRNA-induced RAW 264.7 cells (P < 0.05). In conclusion, wogonin has anti-inflammatory properties related with its inhibition of nitric oxide, cytokines, chemokines, and growth factors in dsRNA-induced macrophages via the calcium-STAT pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessReview Predicting the Uncertain Future of Aptamer-Based Diagnostics and Therapeutics
Molecules 2015, 20(4), 6866-6887; https://doi.org/10.3390/molecules20046866
Received: 19 March 2015 / Revised: 4 April 2015 / Accepted: 7 April 2015 / Published: 16 April 2015
Cited by 46 | PDF Full-text (1435 KB) | HTML Full-text | XML Full-text
Abstract
Despite the great promise of nucleic acid aptamers in the areas of diagnostics and therapeutics for their facile in vitro development, lack of immunogenicity and other desirable properties, few truly successful aptamer-based products exist in the clinical or other markets. Core reasons for
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Despite the great promise of nucleic acid aptamers in the areas of diagnostics and therapeutics for their facile in vitro development, lack of immunogenicity and other desirable properties, few truly successful aptamer-based products exist in the clinical or other markets. Core reasons for these commercial deficiencies probably stem from industrial commitment to antibodies including a huge financial investment in humanized monoclonal antibodies and a general ignorance about aptamers and their performance among the research and development community. Given the early failures of some strong commercial efforts to gain government approval and bring aptamer-based products to market, it may seem that aptamers are doomed to take a backseat to antibodies forever. However, the key advantages of aptamers over antibodies coupled with niche market needs that only aptamers can fill and more recent published data still point to a bright commercial future for aptamers in areas such as infectious disease and cancer diagnostics and therapeutics. As more researchers and entrepreneurs become familiar with aptamers, it seems inevitable that aptamers will at least be considered for expanded roles in diagnostics and therapeutics. This review also examines new aptamer modifications and attempts to predict new aptamer applications that could revolutionize biomedical technology in the future and lead to marketed products. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
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