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Molecules, Volume 18, Issue 8 (August 2013), Pages 8712-10094

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Open AccessArticle Halogen Bonding in (Z)-2-Iodocinnamaldehyde
Molecules 2013, 18(8), 8712-8724; doi:10.3390/molecules18088712
Received: 24 May 2013 / Revised: 11 July 2013 / Accepted: 18 July 2013 / Published: 24 July 2013
Cited by 2 | PDF Full-text (511 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Based on the bulkiness of the iodine atom, a non-planar conformation was expected for the title compound. Instead, its molecular structure is planar, as experimentally determined using single crystal X-ray diffraction, and confirmed theoretically by DFT calculations on the single molecule and the
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Based on the bulkiness of the iodine atom, a non-planar conformation was expected for the title compound. Instead, its molecular structure is planar, as experimentally determined using single crystal X-ray diffraction, and confirmed theoretically by DFT calculations on the single molecule and the halogen pair paired molecules, therefore ruling out crystal packing forces as a principal factor leading to planarity. Indeed, planarity is ascribed to the carbonyl double bond, as when this bond is saturated on forming the related alcohol derivative, the molecule loses planarity. The X-ray molecular structure shows an intermolecular separation between the iodine and the oxygen of the carbonyl shorter than the corresponding van der Waals distance suggesting a weak halogen bond interaction. DFT minimization of this 2-molecule arrangement shows the iodine--oxygen distance much shorter than that observed in the crystal interaction and confirming its stronger halogen bond nature. A trend between increasing I•••O(carbonyl) separation and decreasing C-I•••O(carbonyl) angle is demonstrated, further confirming the existence of a halogen bond. Full article
(This article belongs to the Special Issue Halogen Bond: Application and Prospect)
Open AccessArticle Polyphenolic Composition, Antioxidant and Antibacterial Activities for Two Romanian Subspecies of Achillea distans Waldst. et Kit. ex Willd.
Molecules 2013, 18(8), 8725-8739; doi:10.3390/molecules18088725
Received: 1 July 2013 / Revised: 18 July 2013 / Accepted: 18 July 2013 / Published: 24 July 2013
Cited by 25 | PDF Full-text (246 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this work was to study the chemical composition, antioxidant and antibacterial properties of Achillea distans Waldst. et Kit. subsp. distans and Achillea distans Waldst. et Kit. subsp. alpina Rochel, from the Rodna Mountains (Romania). The identification and quantification of major
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The aim of this work was to study the chemical composition, antioxidant and antibacterial properties of Achillea distans Waldst. et Kit. subsp. distans and Achillea distans Waldst. et Kit. subsp. alpina Rochel, from the Rodna Mountains (Romania). The identification and quantification of major phenolic compounds was performed by a HPLC-MS method. The total polyphenolic and flavonoid content was determined spectrophotometrically. The antioxidant activity was evaluated using the DPPH bleaching method, trolox equivalent antioxidant capacity assay (TEAC), hemoglobin ascorbate peroxidase activity inhibition (HAPX) assay, and an Electron Paramagnetic Resonance (EPR) spectroscopy method. A data indicated that A. distans subsp. alpina extract has more antioxidant activity than A. distans subsp. distans extract. Luteolin, apigenin, quercetin, caffeic and chlorogenic acids were present in the two extracts of A. distans, but in different amounts. Three flavonoids were detected only in A. distans subsp. alpina. The polyphenol-richer A. distans subsp. alpina extract showed a higher antioxidant activity than A. distans subsp. distans extract. A. distans subsp. distans extract showed inhibitory activity for Gram-positive bacteria, as evaluated with four species. The quantitative and qualitative differences between the two subspecies of Achillea distans could be used as a potential taxonomic marker in order to distinguish the species. Full article
Open AccessArticle Oligo-Carrageenans Enhance Growth and Contents of Cellulose, Essential Oils and Polyphenolic Compounds in Eucalyptus globulus Trees
Molecules 2013, 18(8), 8740-8751; doi:10.3390/molecules18088740
Received: 31 May 2013 / Revised: 5 July 2013 / Accepted: 18 July 2013 / Published: 24 July 2013
Cited by 7 | PDF Full-text (342 KB) | HTML Full-text | XML Full-text
Abstract
Eucalyptus globulus (Myrtaceae) originated in Australia and has been introduced in countries with temperate weather in order to obtain wood for cellulose extraction and building purposes. In this work, we analyzed the potential stimulation of growth in height and trunk diameter as well
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Eucalyptus globulus (Myrtaceae) originated in Australia and has been introduced in countries with temperate weather in order to obtain wood for cellulose extraction and building purposes. In this work, we analyzed the potential stimulation of growth in height and trunk diameter as well as the content of holo-cellulose, α-cellulose (long cellulose chains), essential oils and polyphenolic compounds (PPCs) in E. globulus trees treated with oligo-carrageenans (OCs) kappa, lambda and iota, at 1 mg mL−1, once a week, four times in total and then cultivated for three additional years without further treatment. Eucalyptus treated with OCs kappa, lambda and iota showed an increase in height, mainly with OCs kappa and iota by 58% and 47%, respectively, and in trunk diameter by 44% and 40%, respectively. In addition, OCs induced an increase in the contents of holo-cellulose and α-cellulose, mainly OCs kappa and iota which increased holo-cellulose by 8% and 5%, respectively, and α-cellulose by 16 and 13%, respectively. Moreover, OCs increased the content of essential oils, mainly OCs kappa and iota by 67% and 39%, respectively. Furthermore, OCs decreased the concentration of total phenolic compounds but differentially changed the concentration of several PPCs such as genistein, rutin, ellagic acid, morin, luteolin and quercetin with potential antimicrobial activities. Thus, marine algae OCs kappa, lambda and iota stimulate growth of E. globulus trees by enhancing height and trunk diameter as well as the content of α-cellulose, total essential oils, and some PPCs with potential antimicrobial activities. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Two Anti-inflammatory Steroidal Saponins from Dracaena angustifolia Roxb.
Molecules 2013, 18(8), 8752-8763; doi:10.3390/molecules18088752
Received: 18 June 2013 / Revised: 11 July 2013 / Accepted: 21 July 2013 / Published: 24 July 2013
Cited by 5 | PDF Full-text (316 KB) | HTML Full-text | XML Full-text
Abstract
Two new steroidal saponins, named drangustosides A–B (12), together with eight known compounds 310 were isolated and characterized from the MeOH extract of Dracaena angustifolia Roxb. The structures of compounds were assigned based on 1D and 2D
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Two new steroidal saponins, named drangustosides A–B (12), together with eight known compounds 310 were isolated and characterized from the MeOH extract of Dracaena angustifolia Roxb. The structures of compounds were assigned based on 1D and 2D NMR spectroscopic analyses, including HMQC, HMBC, and NOESY. Compounds 1 and 2 showed anti-inflammatory activity by superoxide generation and elastase release by human neutrophils in response to fMLP/CB. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Panduratin A, a Possible Inhibitor in Metastasized A549 Cells through Inhibition of NF-Kappa B Translocation and Chemoinvasion
Molecules 2013, 18(8), 8764-8778; doi:10.3390/molecules18088764
Received: 3 May 2013 / Revised: 21 June 2013 / Accepted: 28 June 2013 / Published: 24 July 2013
Cited by 6 | PDF Full-text (1761 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity
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In the present study, we investigated the effects of panduratin A (PA), isolated from Boesenbergia rotunda, on apoptosis and chemoinvasion in A549 human non-small cell lung cancer cells. Activation of the executioner procaspase-3 by PA was found to be dose-dependent. Caspase-3 activity was significantly elevated at the 5 µg/mL level of PA treatment and progressed to a maximal level. However, no significant elevated level was detected on procaspase-8. These findings suggest that PA activated caspase-3 but not caspase-8. Numerous nuclei of PA treated A549 cells stained brightly by anti-cleaved PARP antibody through High Content Screening. This result further confirmed that PA induced apoptotic cell death was mediated through activation of caspase-3 and eventually led to PARP cleavage. Treatment of A549 cells with PA resulted in a strong inhibition of NF-κB activation, which was consistent with a decrease in nuclear levels of NF-κB/p65 and NF-κB/p50 and the elevation of p53 and p21. Besides that, we also showed that PA significantly inhibited the invasion of A549 cells in a dose-dependent manner through reducing the secretion of MMP-2 of A549 cells gelatin zymography assay. Our findings not only provide the effects of PA, but may also be important in the design of therapeutic protocols that involve targeting of either p53 or NF-κB. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Facile Synthesis of α-N-Ribosyl-Asparagine and α-N-Ribosyl-Glutamine Building Blocks
Molecules 2013, 18(8), 8779-8785; doi:10.3390/molecules18088779
Received: 2 July 2013 / Revised: 16 July 2013 / Accepted: 19 July 2013 / Published: 24 July 2013
Cited by 3 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text
Abstract
Adenosine diphosphate ribosylation (ADP-ribosylation) is a widely occurring post-translational modification of proteins at nucleophilic side chain of amino acid residues. Elucidation of ADP-ribosylation events would benefit greatly from the availability of well-defined ADP-ribosylated peptides and analogues thereof. In this paper we present a
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Adenosine diphosphate ribosylation (ADP-ribosylation) is a widely occurring post-translational modification of proteins at nucleophilic side chain of amino acid residues. Elucidation of ADP-ribosylation events would benefit greatly from the availability of well-defined ADP-ribosylated peptides and analogues thereof. In this paper we present a novel approach to the chemical synthesis of ribosylated amino acid building blocks using traceless Staudinger ligation. We describe an efficient and stereoselective synthesis of α-N-ribosyl-asparagine (α-N-ribosyl-Asn) and α-N-ribosyl-glutamine (α-N-ribosyl-Gln) building blocks starting from 5-tert-butyldiphenylsilyl-β-d-ribofuranosyl azide. The N-glycosyl aminoacids are produced in good yields as pure α-anomers, suitably protected for peptide synthesis. Full article
(This article belongs to the Special Issue ECSOC-16)
Open AccessArticle Isoliquiritigen Enhances the Antitumour Activity and Decreases the Genotoxic Effect of Cyclophosphamide
Molecules 2013, 18(8), 8786-8798; doi:10.3390/molecules18088786
Received: 3 May 2013 / Revised: 16 July 2013 / Accepted: 22 July 2013 / Published: 24 July 2013
Cited by 12 | PDF Full-text (1441 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to evaluate the antitumour activities and genotoxic effects of isoliquiritigenin (ISL) combined with cyclophosphamide (CP) in vitro and in vivo. U14 cells were treated with either of ISL (5–25 μg/mL) or CP (0.25–1.25 mg/mL) alone or
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The aim of this study was to evaluate the antitumour activities and genotoxic effects of isoliquiritigenin (ISL) combined with cyclophosphamide (CP) in vitro and in vivo. U14 cells were treated with either of ISL (5–25 μg/mL) or CP (0.25–1.25 mg/mL) alone or with combination of ISL (5–25 μg/mL) and CP (1.0 mg/mL) for 48 h. The proliferation inhibitory effect in vitro was evaluated by MTT and colony formation assays. KM mice bearing U14 mouse cervical cancer cells were used to estimate the antitumour activity in vivo. The genotoxic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronuclei. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis. The results showed that ISL enhanced antitumour activity of CP in vitro and in vivo, and decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Holographic Quantitative Structure-Activity Relationships of Tryptamine Derivatives at NMDA, 5HT1A and 5HT2A Receptors
Molecules 2013, 18(8), 8799-8811; doi:10.3390/molecules18088799
Received: 10 May 2013 / Revised: 17 July 2013 / Accepted: 18 July 2013 / Published: 24 July 2013
Cited by 2 | PDF Full-text (2374 KB) | HTML Full-text | XML Full-text
Abstract
Tryptamine derivatives (Ts) were found to inhibit the binding of [3H]MK-801, [3H]ketanserin and [3H]8-OH-DPAT to rat brain membranes. [3H]MK-801 labels the NMDA (N-methyl-D-aspartate) receptor, a ionotropic glutamate receptor which controls synaptic plasticity and memory function
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Tryptamine derivatives (Ts) were found to inhibit the binding of [3H]MK-801, [3H]ketanserin and [3H]8-OH-DPAT to rat brain membranes. [3H]MK-801 labels the NMDA (N-methyl-D-aspartate) receptor, a ionotropic glutamate receptor which controls synaptic plasticity and memory function in the brain, whereas [3H]ketanserin and [3H]8-OH-DPAT label 5HT2A and 5HT1A receptors, respectively. The inhibitory potencies of 64 Ts (as given by IC50 values) were correlated with their structural properties by using the Holographic QSAR procedure (HQSAR). This method uses structural fragments and connectivities as descriptors which were encoded in a hologram thus avoiding the usual problems with conformation and alignment of the structures. Four correlation equations with high predictive ability and appropriate statistical test values could be established. The results are visualized by generation of maps reflecting the contribution of individual structural parts to the biological activities. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis and Characterization of Some New Cu(II), Ni(II) and Zn(II) Complexes with Salicylidene Thiosemicarbazones: Antibacterial, Antifungal and in Vitro Antileukemia Activity
Molecules 2013, 18(8), 8812-8836; doi:10.3390/molecules18088812
Received: 29 May 2013 / Revised: 12 July 2013 / Accepted: 15 July 2013 / Published: 24 July 2013
Cited by 19 | PDF Full-text (313 KB) | HTML Full-text | XML Full-text
Abstract
Thirty two new Cu(II), Ni(II) and Zn(II) complexes (132) with salicylidene thiosemicarbazones (H2L1H2L10) were synthesized. Salicylidene thiosemicarbazones, of general formula (X)N-NH-C(S)-NH(Y), were prepared through the condensation reaction of 2-hydroxybenzaldehyde
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Thirty two new Cu(II), Ni(II) and Zn(II) complexes (132) with salicylidene thiosemicarbazones (H2L1H2L10) were synthesized. Salicylidene thiosemicarbazones, of general formula (X)N-NH-C(S)-NH(Y), were prepared through the condensation reaction of 2-hydroxybenzaldehyde and its derivatives (X) with thiosemicarbazide or 4-phenylthiosemicarbazide (Y = H, C6H5). The characterization of the new formed compounds was done by 1H-NMR, 13C-NMR, IR spectroscopy, elemental analysis, magnetochemical, thermoanalytical and molar conductance measurements. In addition, the structure of the complex 5 has been determined by X-ray diffraction method. All ligands and metal complexes were tested as inhibitors of human leukemia (HL-60) cells growth and antibacterial and antifungal activities. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Synthesis of Some Monoazo Disperse Dyes Derived from Aminothienochromene
Molecules 2013, 18(8), 8837-8844; doi:10.3390/molecules18088837
Received: 6 June 2013 / Revised: 16 July 2013 / Accepted: 17 July 2013 / Published: 25 July 2013
Cited by 2 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
A series of azo disperse dyes based on aminothienochromene were synthesized. The fastness properties of the dyed samples were measured. Most of the dyed fabrics tested displayed excellent washing and perspiration fastness and moderate light fastness. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Efficient Synthesis of 2-Amino-6-Arylbenzothiazoles via Pd(0) Suzuki Cross Coupling Reactions: Potent Urease Enzyme Inhibition and Nitric Oxide Scavenging Activities of the Products
Molecules 2013, 18(8), 8845-8857; doi:10.3390/molecules18088845
Received: 21 May 2013 / Revised: 24 June 2013 / Accepted: 9 July 2013 / Published: 25 July 2013
Cited by 8 | PDF Full-text (248 KB) | HTML Full-text | XML Full-text
Abstract
In general, benzothiazole derivatives have attracted great interest due to thier pharmaceutical and biological importance. New 2-amino-6-arylbenzothiazoles were synthesized in moderate to excellent yields via Suzuki cross coupling reactions using various aryl boronic acids and aryl boronic acid pinacol esters and the antiurease
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In general, benzothiazole derivatives have attracted great interest due to thier pharmaceutical and biological importance. New 2-amino-6-arylbenzothiazoles were synthesized in moderate to excellent yields via Suzuki cross coupling reactions using various aryl boronic acids and aryl boronic acid pinacol esters and the antiurease and nitric oxide (NO) scavenging activity of the products were also examined. The most active compound concerning urease enzyme inhibition was 6-phenylbenzo[d]thiazole-2-amine 3e, with an IC50 value of 26.35 µg/mL. Compound 3c, 6-(4-methoxyphenyl) benzo[d]thiazole-2-amine, exhibited the highest nitric oxide percentage scavenging at 100µg/mL. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Glutathione and the Antioxidant Potential of Binary Mixtures with Flavonoids: Synergisms and Antagonisms
Molecules 2013, 18(8), 8858-8872; doi:10.3390/molecules18088858
Received: 5 June 2013 / Revised: 10 July 2013 / Accepted: 22 July 2013 / Published: 25 July 2013
Cited by 14 | PDF Full-text (501 KB) | HTML Full-text | XML Full-text
Abstract
Polyphenols are able to trap free radicals, which contributes to their known antioxidant capacity. In plant extracts, these secondary metabolites may act in concert, in a way that their combined activities will be superior to their individual effects (synergistic interaction). Several polyphenols have
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Polyphenols are able to trap free radicals, which contributes to their known antioxidant capacity. In plant extracts, these secondary metabolites may act in concert, in a way that their combined activities will be superior to their individual effects (synergistic interaction). Several polyphenols have demonstrated clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. As so, the intake of these compounds at certain concentrations in the diet and/or supplementation may potentiate the activity of reduced form glutathione (GSH), thus better fighting oxidative stress. The aim of this work was to predict a structure-antioxidant activity relationship using different classes of flavonoids and to assess, for the first time, possible synergisms and antagonisms with GSH. For these purposes a screening microassay involving the scavenging of DPPH was applied. In general, among the tested compounds, those lacking the catechol group in B ring showed antagonistic behaviour with GSH. Myricetin displayed additive effect, while quercetin, fisetin, luteolin, luteolin-7-O-glucoside, taxifolin and (+)-catechin demonstrated synergistic actions. Furthermore, adducts formed at C2′ and C5′ of the B ring seem to be more important for the antioxidant capacity than adducts formed at C6 and C8 of the A ring. Full article
Open AccessArticle Targeting the Mitochondrial Respiratory Chain of Cryptococcus through Antifungal Chemosensitization: A Model for Control of Non-Fermentative Pathogens
Molecules 2013, 18(8), 8873-8894; doi:10.3390/molecules18088873
Received: 4 July 2013 / Revised: 19 July 2013 / Accepted: 22 July 2013 / Published: 25 July 2013
Cited by 5 | PDF Full-text (719 KB) | HTML Full-text | XML Full-text
Abstract
Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain (MRC) inhibition compared to species of Candida
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Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain (MRC) inhibition compared to species of Candida. This higher sensitivity results from the inability of Cryptococcus to generate cellular energy through fermentation. To heighten disruption of cellular MRC, octyl gallate (OG) or 2,3-dihydroxybenzaldehyde (2,3-DHBA), phenolic compounds inhibiting mitochondrial functions, were selected as chemosensitizers to pyraclostrobin (PCS; an inhibitor of complex III of MRC). The cryptococci were more susceptible to the chemosensitization (i.e., PCS + OG or 2,3-DHBA) than the Candida with all Cryptococcus strains tested being sensitive to this chemosensitization. Alternatively, only few of the Candida strains showed sensitivity. OG possessed higher chemosensitizing potency than 2,3-DHBA, where the concentration of OG required with the drug to achieve chemosensitizing synergism was much lower than that required of 2,3-DHBA. Bioassays with gene deletion mutants of the model yeast Saccharomyces cerevisiae showed that OG or 2,3-DHBA affect different cellular targets. These assays revealed mitochondrial superoxide dismutase or glutathione homeostasis plays a relatively greater role in fungal tolerance to 2,3-DHBA or OG, respectively. These findings show that application of chemosensitizing compounds that augment MRC debilitation is a promising strategy to antifungal control against yeast pathogens. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antifungals)
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Open AccessArticle Antidiarrheal Activity of 19-Deoxyicetexone Isolated from Salvia ballotiflora Benth in Mice and Rats
Molecules 2013, 18(8), 8895-8905; doi:10.3390/molecules18088895
Received: 16 June 2013 / Revised: 17 July 2013 / Accepted: 23 July 2013 / Published: 26 July 2013
Cited by 7 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
The antidiarrheal properties of 19-deoxyicetexone, a diterpenoid isolated from Salvia ballotiflora were evaluated on castor oil-, arachidonic acid (AA)- and prostaglandin (PGE2)-induced diarrhea in rodent models. The structure of 19-deoxyicetexone was determined by X-ray crystallography, mass spectrometry (EI-MS), as well as
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The antidiarrheal properties of 19-deoxyicetexone, a diterpenoid isolated from Salvia ballotiflora were evaluated on castor oil-, arachidonic acid (AA)- and prostaglandin (PGE2)-induced diarrhea in rodent models. The structure of 19-deoxyicetexone was determined by X-ray crystallography, mass spectrometry (EI-MS), as well as ultraviolet (UV-Vis), infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. This compound significantly and dose-dependently reduced frequency of stooling in castor oil-induced diarrhea, and at dose of 25 mg/kg it also inhibited diarrhea induced with AA, while it had no effect on PGE2-induced diarrhea. This compound at doses of 25 mg/kg also diminished castor oil-induced enteropooling and intestinal motility, and inhibited the contraction of the rats’ ileum induced by carbachol chloride at a concentration of 100 µg/mL. 19-Deoxyicetexone did not present acute toxicity at doses of 625 mg/kg. Its antidiarrheal activity may be due to increased reabsorption of NaCl and water and inhibition of the release of prostaglandins, gastrointestinal motility and fluid accumulation in the intestinal tracts of rats. These findings suggest that 19-deoxyicetexone may be used in the treatment of diarrhea, although more studies must be carried out to confirm this. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle NMR Solution Structure of a Chymotrypsin Inhibitor from the Taiwan Cobra Naja naja atra
Molecules 2013, 18(8), 8906-8918; doi:10.3390/molecules18088906
Received: 14 June 2013 / Revised: 19 July 2013 / Accepted: 22 July 2013 / Published: 26 July 2013
Cited by 2 | PDF Full-text (1686 KB) | HTML Full-text | XML Full-text
Abstract
The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the
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The Taiwan cobra (Naja naja atra) chymotrypsin inhibitor (NACI) consists of 57 amino acids and is related to other Kunitz-type inhibitors such as bovine pancreatic trypsin inhibitor (BPTI) and Bungarus fasciatus fraction IX (BF9), another chymotrypsin inhibitor. Here we present the solution structure of NACI. We determined the NMR structure of NACI with a root-mean-square deviation of 0.37 Å for the backbone atoms and 0.73 Å for the heavy atoms on the basis of 1,075 upper distance limits derived from NOE peaks measured in its NOESY spectra. To investigate the structural characteristics of NACI, we compared the three-dimensional structure of NACI with BPTI and BF9. The structure of the NACI protein comprises one 310-helix, one α-helix and one double-stranded antiparallel β-sheet, which is comparable with the secondary structures in BPTI and BF9. The RMSD value between the mean structures is 1.09 Å between NACI and BPTI and 1.27 Å between NACI and BF9. In addition to similar secondary and tertiary structure, NACI might possess similar types of protein conformational fluctuations as reported in BPTI, such as Cys14–Cys38 disulfide bond isomerization, based on line broadening of resonances from residues which are mainly confined to a region around the Cys14–Cys38 disulfide bond. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessArticle Well-Defined Diimine Copper(I) Complexes as Catalysts in Click Azide-Alkyne Cycloaddition Reactions
Molecules 2013, 18(8), 8919-8928; doi:10.3390/molecules18088919
Received: 29 June 2013 / Revised: 21 July 2013 / Accepted: 23 July 2013 / Published: 26 July 2013
Cited by 5 | PDF Full-text (240 KB) | HTML Full-text | XML Full-text
Abstract
A series of 1,4-disubstituted 1,2,3-triazoles have been prepared in high yields while respecting the stringent Click criteria. In these reactions, highly stable pre-formed complexes bearing diimine ligands were used. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessArticle Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts
Molecules 2013, 18(8), 8945-8958; doi:10.3390/molecules18088945
Received: 21 June 2013 / Revised: 12 July 2013 / Accepted: 24 July 2013 / Published: 26 July 2013
Cited by 3 | PDF Full-text (426 KB) | HTML Full-text | XML Full-text
Abstract
In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study
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In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 µg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Luminescence Properties of Iridium(III) Azide- and Triazole-Bisterpyridine Complexes
Molecules 2013, 18(8), 8959-8975; doi:10.3390/molecules18088959
Received: 5 July 2013 / Revised: 24 July 2013 / Accepted: 24 July 2013 / Published: 26 July 2013
Cited by 7 | PDF Full-text (717 KB) | HTML Full-text | XML Full-text
Abstract
We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the “chemistry on the complex” strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition “click chemistry” reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including
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We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the “chemistry on the complex” strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition “click chemistry” reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III) bisterpyridines, but this effect can be reversed by the addition of copper(II) sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III) bisterpyridines can be functionalized for use in “click chemistry” facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
Open AccessArticle Fructus Gardenia Extract Ameliorates Oxonate-Induced Hyperuricemia with Renal Dysfunction in Mice by Regulating Organic Ion Transporters and mOIT3
Molecules 2013, 18(8), 8976-8993; doi:10.3390/molecules18088976
Received: 17 June 2013 / Revised: 19 July 2013 / Accepted: 23 July 2013 / Published: 29 July 2013
Cited by 5 | PDF Full-text (537 KB) | HTML Full-text | XML Full-text
Abstract
The potent anti-hyperuricemia activities of Fructus Gardenia Extract (FGE) have been well reported. The aim of this study was to evaluate the uricosuric and nephro-protective effects of FGE and explore its possible mechanisms of action in oxonate-induced hyperuricemic mice. FGE was orally administered
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The potent anti-hyperuricemia activities of Fructus Gardenia Extract (FGE) have been well reported. The aim of this study was to evaluate the uricosuric and nephro-protective effects of FGE and explore its possible mechanisms of action in oxonate-induced hyperuricemic mice. FGE was orally administered to hyperuricemic and normal mice for 1 week. Serum and urinary levels of uric acid, creatinine and blood urea nitrogen (BUN), and fractional excretion of uric acid (FEUA) were measured. The mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), ATP-binding cassette, subfamily G, 2 (mABCG2), organic anion transporter 1 (mOAT1), mOAT3, oncoprotein induced transcript 3 (mOIT3), organic cation/carnitine transporters in the kidney were analyzed. Simultaneously, Tamm-Horsfall glycoprotein (THP) levels in urine and kidney were detected. FGE significantly reduced serum urate levels and increased urinary urate levels and FEUA in hyperuricemic mice. It could also effectively reverse oxonate-induced alterations in renal mURAT1, mGLUT9, mOAT1 and mOIT3 expressions, as well as THP levels, resulting in the enhancement of renal uric acid excretion. Moreover, FGE decreased serum creatinine and BUN levels, and up-regulated expression of organic cation/carnitine transporters, improving renal dysfunction in this model. Furthermore, FGE decreased renal mABCG2 expressions in hyperuricemic mice, contributing to its beneficial actions. However, further investigation is needed in clinical trials of FGE and its bioactive components. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Aporphine Alkaloids from the Leaves of Phoebe grandis (Nees) Mer. (Lauraceae) and Their Cytotoxic and Antibacterial Activities
Molecules 2013, 18(8), 8994-9009; doi:10.3390/molecules18088994
Received: 16 May 2013 / Revised: 16 July 2013 / Accepted: 22 July 2013 / Published: 29 July 2013
Cited by 9 | PDF Full-text (312 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time
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The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 24 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC50 values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 14 with IC50 values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively. However, none of the tested pathogenic bacteria were susceptible towards compounds 2 and 3. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ab Initio Calculations of Possible γ-Gauche Effects in the 13C-NMR for Methine and Carbonyl Carbons in Precise Polyethylene Acrylic Acid Copolymers
Molecules 2013, 18(8), 9010-9020; doi:10.3390/molecules18089010
Received: 23 June 2013 / Revised: 19 July 2013 / Accepted: 23 July 2013 / Published: 29 July 2013
PDF Full-text (908 KB) | HTML Full-text | XML Full-text
Abstract
The impacts of local polymer chain conformations on the methine and carbonyl 13C-NMR chemical shifts for polyethylene acrylic acid p(E-AA) copolymers were predicted using ab initio methods. Using small molecular cluster models, the magnitude and sign of the γ-gauche torsional angle
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The impacts of local polymer chain conformations on the methine and carbonyl 13C-NMR chemical shifts for polyethylene acrylic acid p(E-AA) copolymers were predicted using ab initio methods. Using small molecular cluster models, the magnitude and sign of the γ-gauche torsional angle effect, along with the impact of local tetrahedral structure distortions near the carbonyl group, on the 13C-NMR chemical shifts were determined. These 13C-NMR chemical shift variations were compared to the experimental trends observed for precise p(E-AA) copolymers as a function acid group spacing and degree of zinc-neutralization in the corresponding p(E-AA) ionomers. These ab initio calculations address the future ability of 13C-NMR chemical shift variations to provide information about the local chain conformations in p(E-AA) copolymer materials. Full article
(This article belongs to the Special Issue Computational Chemistry)
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Open AccessArticle Solid-, Solution-, and Gas-state NMR Monitoring of 13C-Cellulose Degradation in an Anaerobic Microbial Ecosystem
Molecules 2013, 18(8), 9021-9033; doi:10.3390/molecules18089021
Received: 27 June 2013 / Revised: 10 July 2013 / Accepted: 19 July 2013 / Published: 29 July 2013
Cited by 15 | PDF Full-text (1616 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Anaerobic digestion of biomacromolecules in various microbial ecosystems is influenced by the variations in types, qualities, and quantities of chemical components. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for characterizing the degradation of solids to gases in anaerobic digestion processes. Here
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Anaerobic digestion of biomacromolecules in various microbial ecosystems is influenced by the variations in types, qualities, and quantities of chemical components. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for characterizing the degradation of solids to gases in anaerobic digestion processes. Here we describe a characterization strategy using NMR spectroscopy for targeting the input solid insoluble biomass, catabolized soluble metabolites, and produced gases. 13C-labeled cellulose produced by Gluconacetobacter xylinus was added as a substrate to stirred tank reactors and gradually degraded for 120 h. The time-course variations in structural heterogeneity of cellulose catabolism were determined using solid-state NMR, and soluble metabolites produced by cellulose degradation were monitored using solution-state NMR. In particular, cooperative changes between the solid NMR signal and 13C-13C/13C-12C isotopomers in the microbial degradation of 13C-cellulose were revealed by a correlation heat map. The triple phase NMR measurements demonstrated that cellulose was anaerobically degraded, fermented, and converted to methane gas from organic acids such as acetic acid and butyric acid. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessArticle Synthesis and Relaxivity Studies of a DOTA-Based Nanomolecular Chelator Assembly Supported by an Icosahedral Closo-B122− -Core for MRI: A Click Chemistry Approach
Molecules 2013, 18(8), 9034-9048; doi:10.3390/molecules18089034
Received: 1 July 2013 / Revised: 23 July 2013 / Accepted: 23 July 2013 / Published: 29 July 2013
Cited by 5 | PDF Full-text (537 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An icosahedral closo-B122 scaffold based nano-sized assembly capable of carrying a high payload of Gd3+-chelates in a sterically crowded configuration is developed by employing the azide-alkyne click reaction. The twelve copies of DO3A-t-Bu-ester ligands were
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An icosahedral closo-B122 scaffold based nano-sized assembly capable of carrying a high payload of Gd3+-chelates in a sterically crowded configuration is developed by employing the azide-alkyne click reaction. The twelve copies of DO3A-t-Bu-ester ligands were covalently attached to an icosahedral closo-B122 core via suitable linkers through click reaction. This nanomolecular structure supporting a high payload of Gd3+-chelate is a new member of the closomer MRI contrast agents that we are currently developing in our laboratory. The per Gd ion relaxivity (r1) of the newly synthesized MRI contrast agent was obtained in PBS, 2% tween/PBS and bovine calf serum using a 7 Tesla micro MRI instrument and was found to be slightly higher (r1 = 4.7 in PBS at 25 °C) compared to the clinically used MRI contrast agents Omniscan (r1 = 4.2 in PBS at 25 °C) and ProHance (r1 = 3.1 in PBS at 25 °C). Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessArticle Determining Chemical Reactivity Driving Biological Activity from SMILES Transformations: The Bonding Mechanism of Anti-HIV Pyrimidines
Molecules 2013, 18(8), 9061-9116; doi:10.3390/molecules18089061
Received: 30 May 2013 / Revised: 22 July 2013 / Accepted: 24 July 2013 / Published: 30 July 2013
Cited by 12 | PDF Full-text (1641 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Assessing the molecular mechanism of a chemical-biological interaction and bonding stands as the ultimate goal of any modern quantitative structure-activity relationship (QSAR) study. To this end the present work employs the main chemical reactivity structural descriptors (electronegativity, chemical hardness, chemical power, electrophilicity) to
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Assessing the molecular mechanism of a chemical-biological interaction and bonding stands as the ultimate goal of any modern quantitative structure-activity relationship (QSAR) study. To this end the present work employs the main chemical reactivity structural descriptors (electronegativity, chemical hardness, chemical power, electrophilicity) to unfold the variational QSAR though their min-max correspondence principles as applied to the Simplified Molecular Input Line Entry System (SMILES) transformation of selected uracil derivatives with anti-HIV potential with the aim of establishing the main stages whereby the given compounds may inhibit HIV infection. The bonding can be completely described by explicitly considering by means of basic indices and chemical reactivity principles two forms of SMILES structures of the pyrimidines, the Longest SMILES Molecular Chain (LoSMoC) and the Branching SMILES (BraS), respectively, as the effective forms involved in the anti-HIV activity mechanism and according to the present work, also necessary intermediates in molecular pathways targeting/docking biological sites of interest. Full article
(This article belongs to the Special Issue Computational Chemistry)
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Open AccessArticle In Vitro Anticariogenic Effects of Drymocallis rupestris Extracts and Their Quality Evaluation by HPLC-DAD-MS3 Analysis
Molecules 2013, 18(8), 9117-9131; doi:10.3390/molecules18089117
Received: 14 June 2013 / Revised: 13 July 2013 / Accepted: 29 July 2013 / Published: 30 July 2013
Cited by 4 | PDF Full-text (734 KB) | HTML Full-text | XML Full-text
Abstract
In this study, for the first time, we investigated in vitro inhibitory effects of Drymocallis rupestris extracts and their subfractions obtained with solvents of different polarity (aqueous, 50% ethanolic, diethyl ether, ethyl acetate and n-butanolic) against bacterial viability and caries virulence factors
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In this study, for the first time, we investigated in vitro inhibitory effects of Drymocallis rupestris extracts and their subfractions obtained with solvents of different polarity (aqueous, 50% ethanolic, diethyl ether, ethyl acetate and n-butanolic) against bacterial viability and caries virulence factors of Streptococcus spp. strains. The diethyl ether subfraction (PRU2) showed bacteriostatic and bactericidal activity against mutans streptococci, with minimum inhibitory concentrations (MICs) in the range of 0.75–1.5 mg/mL and minimum bactericidal concentrations (MBCs) in the range of 1.5–3 mg/mL. Furthermore, PRU2 inhibited biofilm formation by Streptococci in a dose-dependent manner. It was also found that all five D. rupestris preparations exhibited diverse inhibitory effects on de novo synthesis of water-insoluble and water-soluble α-d-glucans by glucosyltransferases of the mutans group streptococci. The phytochemical profile of investigated samples was determined by spectrophotometric and chromatographic (HPLC-DAD-MS3) methods. The high polyphenol (total phenol, phenolic acids, tannins, proantocyanidins, and flavonoids) contents were found which correlated with anticariogenic activity of the analyzed samples. The results demonstrate that D. rupestris extracts and their subfractions could become useful supplements for pharmaceutical products as a new anticariogenic agent in a wide range of oral care products. Further studies are necessary to clarify which phytoconstituents of D. rupestris are responsible for anticaries properties. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Modification of Oil Palm Mesocarp Fiber Characteristics Using Superheated Steam Treatment
Molecules 2013, 18(8), 9132-9146; doi:10.3390/molecules18089132
Received: 2 May 2013 / Revised: 15 July 2013 / Accepted: 16 July 2013 / Published: 30 July 2013
Cited by 36 | PDF Full-text (712 KB) | HTML Full-text | XML Full-text
Abstract
In this study, oil palm mesocarp fiber (OPMF) was treated with superheated steam (SHS) in order to modify its characteristics for biocomposite applications. Treatment was conducted at temperatures 190–230 °C for 1, 2 and 3 h. SHS-treated OPMF was evaluated for its chemical
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In this study, oil palm mesocarp fiber (OPMF) was treated with superheated steam (SHS) in order to modify its characteristics for biocomposite applications. Treatment was conducted at temperatures 190–230 °C for 1, 2 and 3 h. SHS-treated OPMF was evaluated for its chemical composition, thermal stability, morphology and crystallinity. OPMF treated at 230 °C exhibited lower hemicellulose content (9%) compared to the untreated OPMF (33%). Improved thermal stability of OPMF was found after the SHS treatment. Moreover, SEM and ICP analyses of SHS-treated OPMF showed that silica bodies were removed from OPMF after the SHS treatment. XRD results exhibited that OPMF crystallinity increased after SHS treatment, indicating tougher fiber properties. Hemicellulose removal makes the fiber surface more hydrophobic, whereby silica removal increases the surface roughness of the fiber. Overall, the results obtained herewith suggested that SHS is an effective treatment method for surface modification and subsequently improving the characteristics of the natural fiber. Most importantly, the use of novel, eco-friendly SHS may contribute to the green and sustainable treatment for surface modification of natural fiber. Full article
Open AccessArticle Synthesis and Biological Properties of Caffeic Acid-PNA Dimers Containing Guanine
Molecules 2013, 18(8), 9147-9162; doi:10.3390/molecules18089147
Received: 24 June 2013 / Revised: 18 July 2013 / Accepted: 29 July 2013 / Published: 31 July 2013
Cited by 1 | PDF Full-text (758 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Caffeic acid (CA; 3,4-dihydroxycinnamic acid) is endowed with high antioxidant activity. CA derivatives (such as amides) have gained a lot of attention due to their antioxidative, antitumor and antimicrobial properties as well as stable characteristics. Caffeoyl-peptide derivatives showed different antioxidant activity depending on
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Caffeic acid (CA; 3,4-dihydroxycinnamic acid) is endowed with high antioxidant activity. CA derivatives (such as amides) have gained a lot of attention due to their antioxidative, antitumor and antimicrobial properties as well as stable characteristics. Caffeoyl-peptide derivatives showed different antioxidant activity depending on the type and the sequence of amino acid used. For these reasons, we decided to combine CA with Peptide Nucleic Acid (PNA) to test whether the new PNA-CA amide derivatives would result in an improvement or gain of CA’s biological (i.e., antioxidant, cytotoxic, cytoprotective) properties. We performed the synthesis and characterization of seven dimer conjugates with various combinations of nucleic acid bases and focused NMR studies on the model compound ga-CA dimer. We demonstrate that PNA dimers containing guanine conjugated to CA exhibited different biological activities depending on composition and sequence of the nucleobases. The dimer ag-CA protected HepG2, SK-B-NE(2), and C6 cells from a cytotoxic dose of hydrogen peroxide (H2O2). Full article
Open AccessArticle Synthesis and SAR Studies of Praziquantel Derivatives with Activity against Schistosoma japonicum
Molecules 2013, 18(8), 9163-9178; doi:10.3390/molecules18089163
Received: 25 June 2013 / Revised: 24 July 2013 / Accepted: 25 July 2013 / Published: 31 July 2013
Cited by 8 | PDF Full-text (626 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis and structure-activity relationship (SAR) studies of praziquantel derivatives with activity against adult Schistosoma japonicum are described. Several of them showed better worm killing activity than praziquantel and could serve as leads for further optimization. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Syzygium jambos and Solanum guaraniticum Show Similar Antioxidant Properties but Induce Different Enzymatic Activities in the Brain of Rats
Molecules 2013, 18(8), 9179-9194; doi:10.3390/molecules18089179
Received: 21 May 2013 / Revised: 9 July 2013 / Accepted: 22 July 2013 / Published: 31 July 2013
Cited by 7 | PDF Full-text (694 KB) | HTML Full-text | XML Full-text
Abstract
Syzygium jambos and Solanum guaraniticum are both employed in Brazil as medicinal plants, even though their potential toxicity is not well established and they are frequently misused. The aim of this study was investigate the effect of the aqueous leaf extracts of
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Syzygium jambos and Solanum guaraniticum are both employed in Brazil as medicinal plants, even though their potential toxicity is not well established and they are frequently misused. The aim of this study was investigate the effect of the aqueous leaf extracts of both plants on δ-aminolevulinate dehydratase (δ-ALA-D) and acetylcholinesterase (AChE) activities and the antioxidant action against oxidative damage induced by sodium nitroprusside in rats, using in vitro assays. In addition, the presence of gallic, caffeic and chlorogenic acids, as well as rutin, quercetin and kaempferol as bioactive compounds in the extracts was identified by HPLC and their levels quantified. The antioxidant activities of both extracts were assessed by their capabilities to scavenge nitric oxide and to inhibit lipid peroxidation. Only Syzygium jambos presented thiol-peroxidase-like activity. Although neither extract affected the AChE activity, the aqueous extract of Solanum guaraniticum inhibited brain δ-ALA-D activity, suggesting a possible impairment effect on the central nervous system. Our results showed that both extracts exhibited efficient free radical scavenger activity and are an interesting source of bioactive compounds, justifying their use in folk medicine, although Solanum guaraniticum extract could have neurotoxicity properties and we therefore suggest that its use should be restricted to ensure the health of the population. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Inhibition of Lipopolysaccharide-Induced Proinflammatory Responses by Buddleja officinalis Extract in BV-2 Microglial Cells via Negative Regulation of NF-kB and ERK1/2 Signaling
Molecules 2013, 18(8), 9195-9206; doi:10.3390/molecules18089195
Received: 11 July 2013 / Revised: 24 July 2013 / Accepted: 25 July 2013 / Published: 31 July 2013
Cited by 18 | PDF Full-text (810 KB) | HTML Full-text | XML Full-text
Abstract
Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to
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Buddleja officinalis has been traditionally used in the supportive treatment of inflammatory and neuronal diseases in Korea and China. Although several reports have shown the anti-inflammatory effects of Buddleja officinalis, the anti-neuroinflammatory effect has remained unclear. In this study, we aimed to investigate the inhibitory effects of flower buds of B. officinalis Maximowicz water extract (BOWE) on LPS-induced inflammatory processes in BV-2 microglial cells. BOWE dose-dependently inhibited the production of nitric oxide as well as iNOS mRNA expression. Moreover, BOWE prevented IL-1β and IL-6 mRNA expression. However, BOWE had no effect on LPS-induced COX-2 or TNF-a mRNA expression. The extract also had no effect on LPS-stimulated p38 MAPK, JNK, and c-Jun phosphorylation, whereas ERK1/2 phosphorylation was strongly inhibited by BOWE. BOWE also inhibited the LPS-induced degradation of IkB-α, and LPS-induced phosphorylation of p65 NF-kB protein. These data indicate that BOWE inhibited the nitric oxide production and pro-inflammatory gene expression in BV-2 microglial cells, possibly through a negative regulation of the NF-kB and ERK1/2 pathways. Further identification of the direct target molecule(s) of BOWE is required to support its use as an anti-neuroinflammatory agent against the neurodegenerative disorders. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle In Vitro Antiprotozoal Activity of Triterpenoid Constituents of Kleinia odora Growing in Saudi Arabia
Molecules 2013, 18(8), 9207-9218; doi:10.3390/molecules18089207
Received: 15 July 2013 / Revised: 28 July 2013 / Accepted: 29 July 2013 / Published: 31 July 2013
Cited by 13 | PDF Full-text (320 KB) | HTML Full-text | XML Full-text
Abstract
Two lupane and four ursane triterpenes, namely epilupeol (1), lupeol acetate (2), ursolic acid (3), brein (4), 3β 11α-dihydroxy urs-12-ene (5) and ursolic acid lactone (6) were isolated from aerial parts
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Two lupane and four ursane triterpenes, namely epilupeol (1), lupeol acetate (2), ursolic acid (3), brein (4), 3β 11α-dihydroxy urs-12-ene (5) and ursolic acid lactone (6) were isolated from aerial parts of Kleinia odora and identified. Compounds 1 and 36 were isolated for the first time from K. odora. The triterpene constituents were investigated for antiprotozoal potential against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxicity was determined against MRC-5 fibroblasts to assess selectivity. The ursane triterpenes were found to be active against more than one type of the tested parasites, with the exception of compound 6. This is also the first report on the occurrence of ursane type triterpenes in the genus Kleinia and their antiprotozoal potential against P. falciparum, L. infantum, T. cruzi, and T. brucei. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Obesity Effect of Artemisia capillaris Extracts in High-Fat Diet-Induced Obese Rats
Molecules 2013, 18(8), 9241-9252; doi:10.3390/molecules18089241
Received: 20 May 2013 / Revised: 10 July 2013 / Accepted: 26 July 2013 / Published: 2 August 2013
Cited by 18 | PDF Full-text (557 KB) | HTML Full-text | XML Full-text
Abstract
This study evaluated the anti-obesity effects of Artemisia capillaris extracts in high-fat diet (HFD)-induced obese rats. After six weeks feeding with HFD, Wistar male rats (12-weeks-old) were divided into three groups: HFD-control group and HFD mixed with 0.4% and 0.8% Artemisia capillaris extracts
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This study evaluated the anti-obesity effects of Artemisia capillaris extracts in high-fat diet (HFD)-induced obese rats. After six weeks feeding with HFD, Wistar male rats (12-weeks-old) were divided into three groups: HFD-control group and HFD mixed with 0.4% and 0.8% Artemisia capillaris extracts treated groups. After seven weeks of treatments, the body weight gain of the 0.4% and 0.8% A. capillaris extracts treated groups were significantly less than that of the HFD-control group by 11.8% and 15.4%, respectively. Also, A. capillaris extracts treated groups showed significantly lower serum TG, TC and LDL-c levels in a dose-related manner, while causing the reverse effect in serum HDL-c, and exhibited a hepatoprotective effects in vivo, indicated by reduced hepatic lipid contents, and serum ALT and AST levels. These results show that A. capillaris extracts may prevent body weight increases and improve dyslipidemia in HFD-induced obese rats by enhancing their lipid metabolism. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Oxidant and Anti-Inflammatory Activities of Inonotus obliquus and Germinated Brown Rice Extracts
Molecules 2013, 18(8), 9293-9304; doi:10.3390/molecules18089293
Received: 13 June 2013 / Revised: 28 July 2013 / Accepted: 30 July 2013 / Published: 2 August 2013
Cited by 7 | PDF Full-text (296 KB) | HTML Full-text | XML Full-text
Abstract
Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on
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Inonotus obliquus (IO) is parasitic mushroom that grows on birch and other trees in Russia, Korea, Europe and United States. However, IO is not readily available for consumption due to its high cost and difficult growth. In this regard, IO was inoculated on germinated brown rice (GBR) in the present study and the antioxidant and anti-inflammatory activities of the IO grown on germinated brown rice (IOGBR) extracts were evaluated extensively and compared with those for IO and GBR. IOGBR showed highest antioxidant activities with scavenging total intracellular ROS and MDA levels as well as increasing the antioxidant enzymes activity in the H2O2-stimulated mice liver. It also exhibited best inflammatory activities by suppressing the proinflammatory mediators such as NO, PGE2, iNOS, COX-2, TNF-α, IL-1β, and IL-6 in an LPS-stimulated RAW 264.7 cell line. This study provides a comparative approach to find out an excellent natural source of antioxidants and anti-inflammatory agent as a dietary supplement. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle An Azabisphosphonate-Capped Poly(phosphorhydrazone) Dendrimer for the Treatment of Endotoxin-Induced Uveitis
Molecules 2013, 18(8), 9305-9316; doi:10.3390/molecules18089305
Received: 15 July 2013 / Revised: 26 July 2013 / Accepted: 1 August 2013 / Published: 5 August 2013
Cited by 12 | PDF Full-text (871 KB) | HTML Full-text | XML Full-text
Abstract
Over the last decade, different types of dendrimers have shown anti-inflammatory properties in their own right. In particular, we have shown that poly(phosphorhydrazone) (PPH) dendrimers are able to foster an efficient anti-inflammatory response in human monocytes and can resolve the main physiopathological features
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Over the last decade, different types of dendrimers have shown anti-inflammatory properties in their own right. In particular, we have shown that poly(phosphorhydrazone) (PPH) dendrimers are able to foster an efficient anti-inflammatory response in human monocytes and can resolve the main physiopathological features of chronic arthritis in mice at 1 mg/kg. Here we afford new insights into the therapeutic potential of an azabisphosphonate-capped dendrimer (dendrimer ABP). We have challenged its anti-inflammatory and immuno-modulatory properties in a robust rat model of acute uveitis induced by lipopolysaccharide (LPS). We show that dendrimer ABP at 2 µg/eye is as efficient as the “gold standard” dexamethasone at 20 µg/eye. We have demonstrated that the effect of dendrimer ABP is mediated at least through an increase of the production of the anti-inflammatory Interleukin(IL)-10 cytokine. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Oligomerization of 10,16-Dihydroxyhexadecanoic Acid and Methyl 10,16-Dihydroxyhexadecanoate Catalyzed by Lipases
Molecules 2013, 18(8), 9317-9333; doi:10.3390/molecules18089317
Received: 16 July 2013 / Revised: 29 July 2013 / Accepted: 30 July 2013 / Published: 5 August 2013
Cited by 4 | PDF Full-text (994 KB) | HTML Full-text | XML Full-text
Abstract
The main monomer of tomato cuticle, 10,16-dihydroxyhexadecanoic acid (10,16-DHPA) and its methyl ester derivative (methyl-10,16-dihydroxyhexadecanote; methyl-10,16-DHHD), were used to study their oligomerization reactions catalyzed by five lipases: Candida antarctica lipase B (CAL-B), Rhizomucor miehei lipase (RM), Thermomyces lanuginosus lipase (TL), Pseudomonas cepacia lipase
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The main monomer of tomato cuticle, 10,16-dihydroxyhexadecanoic acid (10,16-DHPA) and its methyl ester derivative (methyl-10,16-dihydroxyhexadecanote; methyl-10,16-DHHD), were used to study their oligomerization reactions catalyzed by five lipases: Candida antarctica lipase B (CAL-B), Rhizomucor miehei lipase (RM), Thermomyces lanuginosus lipase (TL), Pseudomonas cepacia lipase (PCL) and porcine pancreatic lipase (PPL). For 10,16-DHPA, optimum yields were obtained at 60 °C using toluene and 2-methyl-2-butanol (2M2B) as solvent, while for methyl-10,16-DHHD the bests yields were obtained in toluene and acetonitrile. Both reactions leaded to linear polyesters according to the NMR and FT-IR analysis, and there was no data indicating the presence of branched polymers. Using optimized conditions, poly(10,16-DHPA) and poly(methyl-10,16-DHHD) with Mw = 814 and Mn = 1,206 Da, and Mw = 982 and Mn = 860 Da, respectively, were formed according to their MALDI-TOF MS and ESI-MS data. The self-assembly of the polyesters obtained were analyzed by AFM. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle The Potential of Use Basil and Rosemary Essential Oils as Effective Antibacterial Agents
Molecules 2013, 18(8), 9334-9351; doi:10.3390/molecules18089334
Received: 19 June 2013 / Revised: 30 July 2013 / Accepted: 1 August 2013 / Published: 5 August 2013
Cited by 12 | PDF Full-text (272 KB) | HTML Full-text | XML Full-text
Abstract
The considerable therapeutical problems of persistent infections caused by multidrug-resistant bacterial strains constitute a continuing need to find effective antimicrobial agents. The aim of this study was to demonstrate the activities of basil (Ocimum basilicum L.) and rosemary (Rosmarinus officinalis L.)
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The considerable therapeutical problems of persistent infections caused by multidrug-resistant bacterial strains constitute a continuing need to find effective antimicrobial agents. The aim of this study was to demonstrate the activities of basil (Ocimum basilicum L.) and rosemary (Rosmarinus officinalis L.) essential oils against multidrug- resistant clinical strains of Escherichia coli. A detailed analysis was performed of the resistance of the drug to the strains and their sensitivity to the tested oils. The antibacterial activity of the oils was tested against standard strain Escherichia coli ATCC 25922 as well as 60 other clinical strains of Escherichia coli. The clinical strains were obtained from patients with infections of the respiratory tract, abdominal cavity, urinary tract, skin and from hospital equipment. The inhibition of microbial growth by both essential oils, presented as MIC values, were determined by agar dilution. Susceptibility testing to antibiotics was carried out using disc diffusion. The results showed that both tested essential oils are active against all of the clinical strains from Escherichia coli including extended-spectrum β-lactamase positive bacteria, but basil oil possesses a higher ability to inhibit growth. These studies may hasten the application of essential oils in the treatment and prevention of emergent resistant strains in nosocomial infections. Full article
Open AccessArticle Reactive Oxygen Species Mediate Isoalantolactone-Induced Apoptosis in Human Prostate Cancer Cells
Molecules 2013, 18(8), 9382-9396; doi:10.3390/molecules18089382
Received: 27 May 2013 / Revised: 26 July 2013 / Accepted: 31 July 2013 / Published: 5 August 2013
Cited by 21 | PDF Full-text (2962 KB) | HTML Full-text | XML Full-text
Abstract
Isoalantolactone, a medicinal plant-derived natural compound, is known to induce apoptosis in various cancer cell lines. However, its effect on apoptosis in prostate cancer cells has not been addressed. Thus, we examined the effects of isoalantolactone on prostate cancer cells. It was found
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Isoalantolactone, a medicinal plant-derived natural compound, is known to induce apoptosis in various cancer cell lines. However, its effect on apoptosis in prostate cancer cells has not been addressed. Thus, we examined the effects of isoalantolactone on prostate cancer cells. It was found that isoalantolactone inhibits growth of both androgen-sensitive (LNCaP) as well as androgen-independent (PC3 and DU-145) prostate cancer cells in a dose-dependent manner. Furthermore, our results indicate that isoalantolactone-induced apoptosis in prostate cancer PC3 cells is associated with the generation of ROS and dissipation of mitochondrial membrane potential (Δψm). In addition, isoalantolactone triggers apoptosis in prostate cancer cells via up-regulation of Bax, down-regulation of Bcl-2, survivin, and significant activation of caspase-3. Isoalantolactone-induced apoptosis is markedly abrogated when the cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, suggesting that the apoptosis-inducing effect of isoalantolactone in prostate cancer cells is mediated by reactive oxygen species. These findings indicate that isoalantolactone induces reactive oxygen species-dependent apoptosis in prostate cancer cells via a novel mechanism involving inhibition of survivin and provide the rationale for further in vivo and preclinical investigation of isoalantolactone against human prostate cancer. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antibacterial and Herbicidal Activity of Ring-Substituted 2-Hydroxynaphthalene-1-carboxanilides
Molecules 2013, 18(8), 9397-9419; doi:10.3390/molecules18089397
Received: 22 July 2013 / Revised: 1 August 2013 / Accepted: 2 August 2013 / Published: 6 August 2013
Cited by 22 | PDF Full-text (305 KB) | HTML Full-text | XML Full-text
Abstract
In this study, a series of twenty-two ring-substituted 2-hydroxynaphthalene-1‑carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium marinum, M. kasasii, M. smegmatis. and M.
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In this study, a series of twenty-two ring-substituted 2-hydroxynaphthalene-1‑carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium marinum, M. kasasii, M. smegmatis. and M. avium paratuberculosis. The compounds were also tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 2-Hydroxy-N-phenylnaphthalene-1-carboxanilide and 2-hydroxy-N-(3-trifluoromethylphenyl)naphthalene-1-carboxamide (IC50 = 29 µmol/L) were the most active PET inhibitors. Some of tested compounds showed the antibacterial and antimycobacterial activity against the tested strains comparable or higher than the standards ampicillin or isoniazid. Thus, for example, 2-hydroxy-N-(3-nitrophenyl)naphthalene-1-carboxamide showed MIC = 26.0 µmol/L against methicillin-resistant S. aureus and MIC = 51.9 µmol/L against M. marinum, or 2-hydroxy-N-phenylnaphthalene-1-carboxamide demonstrated MIC = 15.2 µmol/L against M. kansasii. The structure-activity relationships for all compounds are discussed. Full article
Open AccessArticle Synthesis of New Acadesine (AICA-riboside) Analogues Having Acyclic d-Ribityl or 4-Hydroxybutyl Chains in Place of the Ribose
Molecules 2013, 18(8), 9420-9431; doi:10.3390/molecules18089420
Received: 27 May 2013 / Revised: 19 July 2013 / Accepted: 1 August 2013 / Published: 6 August 2013
Cited by 7 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
The antiviral activity of certain acyclic nucleosides drew our attention to the fact that the replacement of the furanose ring by an alkyl group bearing hydroxyl(s) could be a useful structural modification to modulate the biological properties of those nucleosides. Herein, we report
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The antiviral activity of certain acyclic nucleosides drew our attention to the fact that the replacement of the furanose ring by an alkyl group bearing hydroxyl(s) could be a useful structural modification to modulate the biological properties of those nucleosides. Herein, we report on the synthesis of some novel acadesine analogues, where the ribose moiety is mimicked by a d-ribityl or by a hydroxybutyl chain. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Study of the Warner-Bratzler Shear Force, Sensory Analysis and Sarcomere Length as Indicators of the Tenderness of Sun-Dried Beef
Molecules 2013, 18(8), 9432-9440; doi:10.3390/molecules18089432
Received: 9 June 2013 / Revised: 12 July 2013 / Accepted: 16 July 2013 / Published: 7 August 2013
Cited by 4 | PDF Full-text (514 KB) | HTML Full-text | XML Full-text
Abstract
Sun-dried beef is a frequently consumed and valued product in Brazil, however, there have been no scientific studies on its texture. To assess the tenderness of sun-dried beef, an instrumental analysis (Warner-Bratzler Shear Force; WBSF), a sensory analysis (Quantitative Descriptive Analysis; QDA) and
[...] Read more.
Sun-dried beef is a frequently consumed and valued product in Brazil, however, there have been no scientific studies on its texture. To assess the tenderness of sun-dried beef, an instrumental analysis (Warner-Bratzler Shear Force; WBSF), a sensory analysis (Quantitative Descriptive Analysis; QDA) and the sarcomere length (SL) were used as indicators. Significant differences were observed among the sun-dried beef samples. Sample 3 (composed of sun-dried meat purchased at three fairs from Region 3 in the city of João Pessoa-PB) was considered the most tender by the assessors, with a score of 6.7, and its WBSF analysis revealed a maximum value of 2.70 kgf. Additionally, this sample exhibited the highest SL value (1.89 µm). Samples 1 and 2 (composed of sun-dried meat purchased at three fairs from Regions 1 and 2, respectively, in the city of João Pessoa) exhibited very similar tenderness values (WBSF and QDA) but differed in their SL values, which suggested that sample 2 was the least tender. In conclusion, these results demonstrate that the studied parameters are complementary and can be used as tenderness indicators for sun-dried beef. However, although the difference was beyond the detection limit of the assessors and the texturometer, the SL analysis appears to have been the most effective. Full article
Open AccessArticle Electronic Structure and Mesoscopic Simulations of Nonylphenol Ethoxylate Surfactants. A Combined DFT and DPD Study
Molecules 2013, 18(8), 9441-9450; doi:10.3390/molecules18089441
Received: 14 May 2013 / Revised: 5 July 2013 / Accepted: 10 July 2013 / Published: 7 August 2013
Cited by 3 | PDF Full-text (1309 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this work was to gain insight into the effect of ethylene oxide (EO) chains on the properties of a series of nonylphenol ethoxylate (NPE) surfactants. We performed a theoretical study of NPE surfactants by means of density functional theory (DFT)
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The aim of this work was to gain insight into the effect of ethylene oxide (EO) chains on the properties of a series of nonylphenol ethoxylate (NPE) surfactants. We performed a theoretical study of NPE surfactants by means of density functional theory (DFT) and dissipative particle dynamics (DPD). Both approximations were used separately to obtain different properties. Four NPEs were selected for this purpose (EO = 4, 7, 11 and 15 length chains). DFT methods provided some electronic properties that are related to the EO units. One of them is the solvation Gibbs energy, which exhibited a linear trend with EO chain length. DPD calculations allow us to observe the dynamic behavior in water of the NPE surfactants. We propose a coarse-grained model which properly simulates the mesophases of each surfactant. This model can be used in other NPEs applications. Full article
(This article belongs to the Special Issue Computational Chemistry)
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Open AccessArticle Chemical Composition and Cytotoxicity Evaluation of Essential Oil from Leaves of Casearia Sylvestris, Its Main Compound α-Zingiberene and Derivatives
Molecules 2013, 18(8), 9477-9487; doi:10.3390/molecules18089477
Received: 4 June 2013 / Revised: 26 June 2013 / Accepted: 27 June 2013 / Published: 8 August 2013
Cited by 19 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
Casearia sylvestris (Salicaceae), popularly known as “guaçatonga”, is a plant widely used in folk medicine to treat various diseases, including cancer. The present work deals with the chemical composition as well as the cytotoxic evaluation of its essential oil, its main constituent and
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Casearia sylvestris (Salicaceae), popularly known as “guaçatonga”, is a plant widely used in folk medicine to treat various diseases, including cancer. The present work deals with the chemical composition as well as the cytotoxic evaluation of its essential oil, its main constituent and derivatives. Thus, the crude essential oil from leaves of C. sylvestris was obtained using a Clevenger type apparatus and analyzed by GC/MS. This analysis afforded the identification of 23 substances, 13 of which corresponded to 98.73% of the total oil composition, with sesquiterpene a-zingiberene accounting for 50% of the oil. The essential oil was evaluated for cytotoxic activity against several tumor cell lines, giving IC50 values ranging from 12 to 153 mg/mL. Pure a-zingiberene, isolated from essential oil, was also evaluated against the tumor cell lines showing activity for HeLa, U-87, Siha and HL60 cell lines, but with IC50 values higher than those determined for the crude essential oil. Aiming to evaluate the effect of the double bonds of a-zingiberene on the cytotoxic activity, partially hydrogenated a-zingiberene (PHZ) and fully hydrogenated a-zingiberene (THZ) derivatives were obtained. For the partially hydrogenated derivative only cytotoxic activity to the B16F10-Nex2 cell line (IC50 65mg/mL) was detected, while totally hydrogenated derivative showed cytotoxic activity for almost all cell lines, with B16F10-Nex2 and MCF-7 as exceptions and with IC50 values ranging from 34 to 65 mg/mL. These results indicate that cytotoxic activity is related with the state of oxidation of compound. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Efficient Synthesis of Boron-Containing α-Acyloxyamide Analogs via Microwave Irradiation
Molecules 2013, 18(8), 9488-9511; doi:10.3390/molecules18089488
Received: 27 June 2013 / Revised: 2 August 2013 / Accepted: 5 August 2013 / Published: 8 August 2013
Cited by 1 | PDF Full-text (601 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this report, a Passerini three-component reaction utilizing boron-containing carboxylic acids or aldehydes is discussed. The reaction was carried out in water and facilitated by the use of microwave irradiation. This methodology allowed for the efficient formation of a broad range of boron-containing
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In this report, a Passerini three-component reaction utilizing boron-containing carboxylic acids or aldehydes is discussed. The reaction was carried out in water and facilitated by the use of microwave irradiation. This methodology allowed for the efficient formation of a broad range of boron-containing α-acyloxyamides under mild conditions within a short time. Two series of boron-containing α-acyloxyamides were synthesized and subsequently screened for cytotoxicity using the MTT cell viability assay. Two potential lead compounds were found to have potent activity against the HepG2 cancer cell line, demonstrating the potential of this methodology for use in the development of novel pharmaceuticals. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Melaleuca alternifolia Concentrate Inhibits in Vitro Entry of Influenza Virus into Host Cells
Molecules 2013, 18(8), 9550-9566; doi:10.3390/molecules18089550
Received: 25 June 2013 / Revised: 18 July 2013 / Accepted: 19 July 2013 / Published: 9 August 2013
Cited by 3 | PDF Full-text (3083 KB) | HTML Full-text | XML Full-text
Abstract
Influenza virus causes high morbidity among the infected population annually and occasionally the spread of pandemics. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has any in vitro inhibitory
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Influenza virus causes high morbidity among the infected population annually and occasionally the spread of pandemics. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has any in vitro inhibitory effect on influenza virus infection and what mechanism does the MAC use to fight the virus infection. In this study, the antiviral activity of MAC was examined by its inhibition of cytopathic effects. In silico prediction was performed to evaluate the interaction between MAC and the viral haemagglutinin. We found that when the influenza virus was incubated with 0.010% MAC for one hour, no cytopathic effect on MDCK cells was found after the virus infection and no immunofluorescence signal was detected in the host cells. Electron microscopy showed that the virus treated with MAC retained its structural integrity. By computational simulations, we found that terpinen-4-ol, which is the major bioactive component of MAC, could combine with the membrane fusion site of haemagglutinin. Thus, we proved that MAC could prevent influenza virus from entering the host cells by disturbing the normal viral membrane fusion procedure. Full article
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Open AccessArticle Accidental Interaction between PDZ Domains and Diclofenac Revealed by NMR-Assisted Virtual Screening
Molecules 2013, 18(8), 9567-9581; doi:10.3390/molecules18089567
Received: 27 June 2013 / Revised: 1 August 2013 / Accepted: 5 August 2013 / Published: 9 August 2013
Cited by 1 | PDF Full-text (2341 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In silico approaches have become indispensable for drug discovery as well as drug repositioning and adverse effect prediction. We have developed the eF-seek program to predict protein–ligand interactions based on the surface structure of proteins using a clique search algorithm. We have also
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In silico approaches have become indispensable for drug discovery as well as drug repositioning and adverse effect prediction. We have developed the eF-seek program to predict protein–ligand interactions based on the surface structure of proteins using a clique search algorithm. We have also developed a special protein structure prediction pipeline and accumulated predicted 3D models in the Structural Atlas of the Human Genome (SAHG) database. Using this database, genome-wide prediction of non-peptide ligands for proteins in the human genome was performed, and a subset of predicted interactions including 14 PDZ domains was then confirmed by NMR titration. Surprisingly, diclofenac, a non-steroidal anti-inflammatory drug, was found to be a non-peptide PDZ domain ligand, which bound to 5 of 15 tested PDZ domains. The critical residues for the PDZ–diclofenac interaction were also determined. Pharmacological implications of the accidental PDZ–diclofenac interaction are further discussed. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessArticle Evaluation of the Effect of Different Growth Media and Temperature on the Suitability of Biofilm Formation by Enterobacter cloacae Strains Isolated from Food Samples in South Africa
Molecules 2013, 18(8), 9582-9593; doi:10.3390/molecules18089582
Received: 20 May 2013 / Revised: 22 July 2013 / Accepted: 23 July 2013 / Published: 9 August 2013
Cited by 6 | PDF Full-text (276 KB) | HTML Full-text | XML Full-text
Abstract
This study evaluated the effects of growth medium, temperature, and incubation time on biofilm formation by Enterobacter cloacae strains. The ability to adhere to a surface was demonstrated using a microtiter plate adherence assay whereas the role of cell surface properties in biofilm
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This study evaluated the effects of growth medium, temperature, and incubation time on biofilm formation by Enterobacter cloacae strains. The ability to adhere to a surface was demonstrated using a microtiter plate adherence assay whereas the role of cell surface properties in biofilm formation was assessed using the coaggregation and autoaggregation assays. The architecture of the biofilms was examined under scanning electron microscope (SEM). All the strains adhered to the well of the microtiter plate when incubated for 48 h, irrespective of the growth medium and incubation temperature. It was also noted that 90% and 73% of strains prepared from nutrient broth and cultured in brain heart infusion (BHI) broth and tryptic soy broth (TSB), respectively, were able to form biofilms, in contrast to 73% and 60% strains from nutrient agar and cultured in BHI and TSB respectively grown under similar conditions. However, no statistically significant difference was observed when the two methods were compared. The coaggregation index ranged from 12% to 74%, with the best coaggregate activity observed when partnered with Streptococcus pyogenes (54%–74%). The study indicates the suitability of BHI and TSB medium for the cultivation of E. cloacae biofilms, however, temperature and incubation time significantly affect biofilm formation by these bacteria. Full article
Open AccessArticle A Facile Fabrication of Alginate Microbubbles Using a Gas Foaming Reaction
Molecules 2013, 18(8), 9594-9602; doi:10.3390/molecules18089594
Received: 17 July 2013 / Revised: 6 August 2013 / Accepted: 7 August 2013 / Published: 12 August 2013
Cited by 7 | PDF Full-text (1094 KB) | HTML Full-text | XML Full-text
Abstract
Microbubble particles have been extensively utilized as temporal templates for various biomedical applications. This study proposes a facile strategy to obtain microbubble-containing alginate particles (i.e., microbubbles inside alginate gel particles, called alginate microbubbles). The chemical reaction of sodium bicarbonate and hydrogen
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Microbubble particles have been extensively utilized as temporal templates for various biomedical applications. This study proposes a facile strategy to obtain microbubble-containing alginate particles (i.e., microbubbles inside alginate gel particles, called alginate microbubbles). The chemical reaction of sodium bicarbonate and hydrogen peroxide to produce gaseous carbon dioxide and oxygen was utilized to form microbubbles within alginate particles. Uniform alginate particles were obtained by a stable needle-based droplet formation process. Kinetic reaction of gas formation was monitored for 2% alginate particles. The gas formation increased with the concentrations of sodium bicarbonate (1–5 wt%) and hydrogen peroxide (0–36.5 wt%). Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Synthesis of Photoresponsive Dual NIR Two-Photon Absorptive [60]Fullerene Triads and Tetrads
Molecules 2013, 18(8), 9603-9622; doi:10.3390/molecules18089603
Received: 18 June 2013 / Revised: 30 July 2013 / Accepted: 5 August 2013 / Published: 12 August 2013
Cited by 2 | PDF Full-text (867 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Broadband nonlinear optical (NLO) organic nanostructures exhibiting both ultrafast photoresponse and a large cross-section of two-photon absorption throughout a wide NIR spectrum may make them suitable for use as nonlinear biophotonic materials. We report here the synthesis and characterization of two C60
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Broadband nonlinear optical (NLO) organic nanostructures exhibiting both ultrafast photoresponse and a large cross-section of two-photon absorption throughout a wide NIR spectrum may make them suitable for use as nonlinear biophotonic materials. We report here the synthesis and characterization of two C60-(antenna)x analogous compounds as branched triad C60(>DPAF-C18)(>CPAF-C2M) and tetrad C60(>DPAF-C18)(>CPAF-C2M)2 nanostructures. These compounds showed approximately equal extinction coefficients of optical absorption over 400–550 nm that corresponds to near-IR two-photon based excitation wavelengths at 780–1,100 nm. Accordingly, they may be utilized as potential precursor candidates to the active-core structures of photosensitizing nanodrugs for 2γ-PDT in the biological optical window of 800–1,050 nm. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Susceptibility of Staphylococcus aureus Clinical Isolates to Propolis Extract Alone or in Combination with Antimicrobial Drugs
Molecules 2013, 18(8), 9623-9640; doi:10.3390/molecules18089623
Received: 6 June 2013 / Revised: 23 July 2013 / Accepted: 26 July 2013 / Published: 12 August 2013
Cited by 18 | PDF Full-text (503 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to assess in vitro the antimicrobial activity of ethanolic extract of Polish propolis (EEPP) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The combined effect of EEPP and 10 selected antistaphylococcal drugs on
[...] Read more.
The objective of this study was to assess in vitro the antimicrobial activity of ethanolic extract of Polish propolis (EEPP) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The combined effect of EEPP and 10 selected antistaphylococcal drugs on S. aureus clinical cultures was also investigated. EEPP composition was analyzed by a High Performance Liquid Chromatography (HPLC) method. The flavonoid compounds identified in Polish Propolis included flavones, flavonones, flavonolols, flavonols and phenolic acids. EEPP displayed varying effectiveness against twelve S. aureus strains, with minimal inhibitory concentration (MIC) within the range from 0.39 to 0.78 mg/mL, determined by broth microdilution method. The average MIC was 0.54 ± 0.22 mg/mL, while calculated MIC50 and MIC90 were 0.39 mg/mL and 0.78 mg/mL, respectively. The minimum bactericidal concentration (MBC) of the EEPP ranged from 0.78 to 3.13 mg/mL. The in vitro combined effect of EEPP and 10 antibacterial drugs was investigated using disk diffusion method-based assay. Addition of EEPP to cefoxitin (FOX), clindamycin (DA), tetracycline (TE), tobramycin (TOB), linezolid (LIN), trimethoprim+sulfamethoxazole (SXT), penicillin (P), erythromycin (E) regimen, yielded stronger, cumulative antimicrobial effect, against all tested S. aureus strains than EEPP and chemotherapeutics alone. In the case of ciprofloxacin (CIP) and chloramphenicol (C) no synergism with EEPP was observed. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Phenylpropanoid, Sapnol A, Lignan and Neolignan Sophorosides, Saposides A and B, Isolated from Canadian Sugar Maple Sap
Molecules 2013, 18(8), 9641-9649; doi:10.3390/molecules18089641
Received: 19 July 2013 / Revised: 7 August 2013 / Accepted: 8 August 2013 / Published: 12 August 2013
Cited by 4 | PDF Full-text (309 KB) | HTML Full-text | XML Full-text
Abstract
One new phenolic compound, sapnol A (1), and two new aromatic sophorosides, named saposides A (2) and B (3) were isolated from sugar maple sap. In addition, seven known phenolic compounds 410 were isolated. These
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One new phenolic compound, sapnol A (1), and two new aromatic sophorosides, named saposides A (2) and B (3) were isolated from sugar maple sap. In addition, seven known phenolic compounds 410 were isolated. These structures were determined on the basis of NMR experiments as well as chemical evidence. Furthermore, all the isolated compounds 110 were tested for antioxidative activity by the superoxide dismutase (SOD)-like assay. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Three Novel Xanthones from Garcinia paucinervis and Their Anti-TMV Activity
Molecules 2013, 18(8), 9663-9669; doi:10.3390/molecules18089663
Received: 6 June 2013 / Revised: 2 August 2013 / Accepted: 5 August 2013 / Published: 13 August 2013
Cited by 15 | PDF Full-text (205 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phytochemical investigations of the leaves of Garcinia paucinervis resulted in the isolation of three new xanthones 13 and five known analogues 48. Structural elucidations of 13 were performed by spectral methods such as 1D and 2D
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Phytochemical investigations of the leaves of Garcinia paucinervis resulted in the isolation of three new xanthones 13 and five known analogues 48. Structural elucidations of 13 were performed by spectral methods such as 1D and 2D (HMQC, HMBC, and ROESY) NMR spectroscopy, in addition to high resolution mass spectrometry. Compounds 13 showed anti-TMV activities, with inhibition rates above 20%, especially for 1, which had a lower IC50 value of 21.4 µM. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Synthesis and the Biological Evaluation of New Thiazolidin-4-one Derivatives Containing a Xanthine Moiety
Molecules 2013, 18(8), 9684-9703; doi:10.3390/molecules18089684
Received: 10 July 2013 / Accepted: 5 August 2013 / Published: 13 August 2013
Cited by 8 | PDF Full-text (440 KB) | HTML Full-text | XML Full-text
Abstract
Starting from theophylline (1,3-dimethylxanthine) new thiazolidin-4-one derivatives 7a1–7, 7b1–7 have been synthesized as potential antidiabetic drugs. The structure of the new derivatives was confirmed using spectral methods (FT-IR, 1H-NMR, 13C-NMR). The in vitro antioxidant potential of the synthesized
[...] Read more.
Starting from theophylline (1,3-dimethylxanthine) new thiazolidin-4-one derivatives 7a1–7, 7b1–7 have been synthesized as potential antidiabetic drugs. The structure of the new derivatives was confirmed using spectral methods (FT-IR, 1H-NMR, 13C-NMR). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing power, the total antioxidant activity and the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be implicated in a variety of pathological events, such as diabetes mellitus and its micro- and macrovascular complications. The results of chemical modulation of the thiazolidin-4-one intermediaries 6a, 6b through condensation with several aromatic aldehydes is the improvement of the antioxidant effect. All benzylidenethiazolidin-4-one derivatives 7a1–7, 7b1–7 are more active than their parent thiazolidin-4-ones. The most active compounds are the ones obtained by reaction of condensation with 4-hydroxybenzaldehyde (compounds 7a5, 7a6), 4-dimethylaminobenzaldehyde (compounds 7a6, 7b6) and 2-nitrobenzaldehyde (compounds 7a7, 7b7). Full article
Open AccessArticle Enzymatic Synthesis of Extremely Pure Triacylglycerols Enriched in Conjugated Linoleic Acids
Molecules 2013, 18(8), 9704-9716; doi:10.3390/molecules18089704
Received: 10 May 2013 / Revised: 5 August 2013 / Accepted: 12 August 2013 / Published: 13 August 2013
Cited by 9 | PDF Full-text (1154 KB) | HTML Full-text | XML Full-text
Abstract
This work was objectively targeted to synthesize extremely pure triacylglycerols (TAG) enriched in conjugated linoleic acids (CLAs) for medical and dietetic purposes. Extremely pure CLA-enriched TAG was successfully synthesized by using the multi-step process: TAG was primarily synthesized by lipase-catalyzed esterification of CLA
[...] Read more.
This work was objectively targeted to synthesize extremely pure triacylglycerols (TAG) enriched in conjugated linoleic acids (CLAs) for medical and dietetic purposes. Extremely pure CLA-enriched TAG was successfully synthesized by using the multi-step process: TAG was primarily synthesized by lipase-catalyzed esterification of CLA and glycerol and then the lower glycerides [monoacylglycerol (MAG) and diacylglycerol (DAG)] in the esterification mixtures was hydrolyzed to free fatty acids (FFAs) by a mono- and di-acylglycerol lipase (lipase SMG1), finally, the FFAs were further separated from TAG by low temperature (150 °C) molecular distillation. The operation parameters for the lipase SMG1-catalyzed hydrolysis were optimized using response surface methodology based on the central composite rotatable design (CCRD). The operation parameters included water content, pH and reaction temperature and all of these three parameters showed significant effects on the hydrolysis of lower glycerides. The optimal conditions were obtained with a water content of 66.4% (w/w, with respect to oil mass), pH at 5.7 and 1 h of reaction time at 19.6 °C. Under these conditions, the content of lower glycerides in the reaction mixture decreased from 45.2% to 0.3% and the purity of CLA-enriched TAG reached 99.7%. Further purification of TAG was accomplished by molecular distillation and the final CLA-enriched TAG product yielded 99.8% of TAG. These extremely pure CLA-enriched TAG would be used for in vivo studies in animals and humans in order to get specific information concerning CLA metabolism. Full article
Open AccessArticle Highly Efficient Biotransformation of Polydatin to Resveratrol by Snailase Hydrolysis Using Response Surface Methodology Optimization
Molecules 2013, 18(8), 9717-9726; doi:10.3390/molecules18089717
Received: 5 June 2013 / Revised: 15 July 2013 / Accepted: 16 July 2013 / Published: 13 August 2013
Cited by 5 | PDF Full-text (790 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (RV), a dietary antioxidant polyphenolic compound found in grapes and red wine, exerts a wide variety of pharmacological activities. However, lower content in plants compared with polydatin (PD, the glucoside of RV) limits its application in the food and pharmaceutical industries. In
[...] Read more.
Resveratrol (RV), a dietary antioxidant polyphenolic compound found in grapes and red wine, exerts a wide variety of pharmacological activities. However, lower content in plants compared with polydatin (PD, the glucoside of RV) limits its application in the food and pharmaceutical industries. In this paper, we carried out efficient biotransformation of PD to RV with 100% conversion yield by snailase hydrolysis. Moreover, response surface methodology (RSM) was used to optimize the effects of the reaction temperature, enzyme load, and reaction time on the conversion process. Validation of the RSM model was verified by the good agreement between the experimental and the predicted RV yield values. The optimum preparation conditions were as follows: temperature of 62.0 °C, enzyme load of 6.6%, and reaction time of 96 min. The proposed method may be highly applicable for the enzymatic preparation of RV for medicinal purposes. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Uncarilic Acid and Secouncarilic Acid, Two New Triterpenoids from Uucaria sessilifructus
Molecules 2013, 18(8), 9727-9734; doi:10.3390/molecules18089727
Received: 29 May 2013 / Revised: 26 July 2013 / Accepted: 29 July 2013 / Published: 14 August 2013
Cited by 3 | PDF Full-text (446 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new compounds, the 6-oxo oleanane-type triterpenoid uncarilic acid, and its 5,6-secotriterpenoid derivative, secouncarilic acid, were isolated from the hooks and stems of Uucaria sessilifructus together with seven known ursane-type triterpenoids. Uncarilic acid is the second 6-oxo oleanane-type triterpenoid ever reported, while secouncarilic
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Two new compounds, the 6-oxo oleanane-type triterpenoid uncarilic acid, and its 5,6-secotriterpenoid derivative, secouncarilic acid, were isolated from the hooks and stems of Uucaria sessilifructus together with seven known ursane-type triterpenoids. Uncarilic acid is the second 6-oxo oleanane-type triterpenoid ever reported, while secouncarilic acid is the first oleanane-type 5,6-secotriterpenoid. A plausible biosynthetic pathway from uncarilic acid to secouncarilic acid was also postulated. The inhibitory activities of all the nine compounds against LPS-induced nitric oxide production in RAW264.7 macrophages were evaluated. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle NMR Study on the Interaction of Trehalose with Lactose and Its Effect on the Hydrogen Bond Interaction in Lactose
Molecules 2013, 18(8), 9735-9754; doi:10.3390/molecules18089735
Received: 20 June 2013 / Revised: 31 July 2013 / Accepted: 7 August 2013 / Published: 14 August 2013
Cited by 5 | PDF Full-text (840 KB) | HTML Full-text | XML Full-text
Abstract
Trehalose, a well-known stress-protector of biomolecules, has been investigated for its effect on the mobility, hydration and hydrogen bond interaction of lactose using diffusion-ordered NMR spectroscopy and NMR of hydroxy protons. In ternary mixtures of trehalose, lactose and water, the two sugars have
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Trehalose, a well-known stress-protector of biomolecules, has been investigated for its effect on the mobility, hydration and hydrogen bond interaction of lactose using diffusion-ordered NMR spectroscopy and NMR of hydroxy protons. In ternary mixtures of trehalose, lactose and water, the two sugars have the same rate of diffusion. The chemical shifts, temperature coefficients, vicinal coupling constants and ROE of the hydroxy protons in trehalose, lactose and sucrose were measured for the disaccharides alone in water/acetone-d6 solutions as well as in mixtures. The data indicated that addition of trehalose did not change significantly the strength of the hydrogen bond interaction between GlcOH3 and GalO5' in lactose. Small upfield shifts were however measured for all hydroxy protons when the sugar concentration was increased. The chemical shift of the GlcOH3 signal in lactose showed less change, attributed to the spatial proximity to GalO5'. Chemical exchange between hydroxy protons of lactose and trehalose was observed in the ROESY NMR spectra. Similar effects were observed with sucrose indicating no specific effect of trehalose at the concentrations investigated (73 to 763 mg/mL) and suggesting that it is the concentration of hydroxy groups more than the type of sugars which is guiding intermolecular interactions. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
Open AccessArticle Characterization of Nucleosides and Nucleobases in Natural Cordyceps by HILIC–ESI/TOF/MS and HILIC–ESI/MS
Molecules 2013, 18(8), 9755-9769; doi:10.3390/molecules18089755
Received: 2 July 2013 / Accepted: 8 August 2013 / Published: 15 August 2013
Cited by 11 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
A method combining hydrophilic interaction chromatography (HILIC) and electrospray ionization mass spectrometry (ESI-MS) was developed for the characterization and determination of natural Cordyceps. Separation was achieved on a Waters Xbridge Amide column with gradient elution. Identification of 15 target nucleosides and nucleobases
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A method combining hydrophilic interaction chromatography (HILIC) and electrospray ionization mass spectrometry (ESI-MS) was developed for the characterization and determination of natural Cordyceps. Separation was achieved on a Waters Xbridge Amide column with gradient elution. Identification of 15 target nucleosides and nucleobases was based on retention time, UV spectra and mass measurements of the protonated molecules ([M+H]+) and main fragment ions (ESI-TOF/MS). Eight non-target compounds were tentatively identified by ESI-TOF/MS. The 15 target compounds were quantified by HILIC-ESI-MS/MS using time-programmed selective ion monitoring or multiple reaction monitoring in positive-ion mode under optimized mass conditions. This technique showed good linearity, repeatability and recovery. This approach was also successfully implemented in the analysis of nucleosides and nucleobases in 12 batches of natural Cordyceps samples that were collected from different regions in China. The developed HILIC-ESI-MS method exhibited clear advantages in identifying and determining highly polar bioactive components in Cordyceps, as well as their quality control. Full article
Open AccessArticle Antidiabetic and Antioxidant Properties of Alkaloids from Catharanthus roseus (L.) G. Don
Molecules 2013, 18(8), 9770-9784; doi:10.3390/molecules18089770
Received: 17 June 2013 / Revised: 2 August 2013 / Accepted: 9 August 2013 / Published: 15 August 2013
Cited by 27 | PDF Full-text (1758 KB) | HTML Full-text | XML Full-text
Abstract
Catharanthus roseus (L.) G. Don is a herbal plant traditionally used by local populations in India, South Africa, China and Malaysia to treat diabetes. The present study reports the in vitro antioxidant and antidiabetic activities of the major alkaloids isolated from Catharanthus roseus
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Catharanthus roseus (L.) G. Don is a herbal plant traditionally used by local populations in India, South Africa, China and Malaysia to treat diabetes. The present study reports the in vitro antioxidant and antidiabetic activities of the major alkaloids isolated from Catharanthus roseus (L.) G. Don leaves extract. Four alkaloids—vindoline I, vindolidine II, vindolicine III and vindolinine IV—were isolated and identified from the dichloromethane extract (DE) of this plant’s leaves. DE and compounds IIII were not cytotoxic towards pancreatic β-TC6 cells at the highest dosage tested (25.0 µg/mL). All four alkaloids induced relatively high glucose uptake in pancreatic β-TC6 or myoblast C2C12 cells, with III showing the highest activity. In addition, compounds IIIV demonstrated good protein tyrosine phosphatase-1B (PTP-1B) inhibition activity, implying their therapeutic potential against type 2 diabetes. III showed the highest antioxidant potential in ORAC and DPPH assays and it also alleviated H2O2-induced oxidative damage in β-TC6 cells at 12.5 µg/mL and 25.0 µg/mL. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Composition and Biological Activities of Essential Oils of Eremanthus erythropappus (DC) McLeisch (Asteraceae)
Molecules 2013, 18(8), 9785-9796; doi:10.3390/molecules18089785
Received: 19 July 2013 / Revised: 6 August 2013 / Accepted: 8 August 2013 / Published: 16 August 2013
Cited by 15 | PDF Full-text (223 KB) | HTML Full-text | XML Full-text
Abstract
The chemical composition of the essential oils obtained by hydrodistillation of different parts of Eremanthus erythropappus, including leaves, branches and inflorescences, was investigated by Gas Chromatography and Gas Chromatography/Mass Spectrometry. The antimicrobial activity of the oils was assessed by the disc diffusion
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The chemical composition of the essential oils obtained by hydrodistillation of different parts of Eremanthus erythropappus, including leaves, branches and inflorescences, was investigated by Gas Chromatography and Gas Chromatography/Mass Spectrometry. The antimicrobial activity of the oils was assessed by the disc diffusion and microdilution methods, while the antioxidant activity was evaluated by DPPH and reducing power tests. The main compounds found in the essential oils derived from the inflorescences and leaves were β-caryophyllene, germacrene-D, α-copaene and β-pinene. α-Bisabolol was the major component in the branches. The oils were active against Staphylococcus aureus, Streptococcus pyogenes and fungi, but not Escherichia coli and Pseudomonas aeruginosa. The MIC values ranged from 0.01 to 0.50 mg/mL. Using the DPPH test, the IC50 values ranged from 38.77 ± 0.76 to 102.24 ± 1.96 μg/mL, while the reducing power test produced IC50 values between 109.85 ± 1.68 and 169.53 ± 0.64 μg/mL. The results revealed that the E. erythropappus oils are new promising potential sources of antimicrobial and antioxidant compounds with good future practical applications for human health. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Eco-Friendly Synthesis and Antiproliferative Evaluation of Some Oxygen Substituted Diaryl Ketones
Molecules 2013, 18(8), 9818-9832; doi:10.3390/molecules18089818
Received: 26 June 2013 / Revised: 5 August 2013 / Accepted: 12 August 2013 / Published: 16 August 2013
Cited by 7 | PDF Full-text (320 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A broad variety of oxygen-substituted diaryl ketones has been synthesized by solar energy-induced Friedel Crafts acylations of 1,4-benzo- and 1,4-naphthoquinones with benzaldehydes. The in vitro antiproliferative properties of the photoproducts were assessed on prostate (DU-145), bladder (T24) and breast (MCF7) human-derived tumor cell
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A broad variety of oxygen-substituted diaryl ketones has been synthesized by solar energy-induced Friedel Crafts acylations of 1,4-benzo- and 1,4-naphthoquinones with benzaldehydes. The in vitro antiproliferative properties of the photoproducts were assessed on prostate (DU-145), bladder (T24) and breast (MCF7) human-derived tumor cell lines and compared to non-tumor mouse fibroblasts (Balb/3T3). Among the tested compounds, it was found that those containing a 3,4,5-trimethoxyphenyl A-ring, such as 12 and 22 are more active on DU-145, with EC50 values of 1.2 and 5.9 μM, respectively. By comparing their effects on the three cancer cell lines, the analogue 22 has the best mean selective index (2.4). Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle ADIBO-Based “Click” Chemistry for Diagnostic Peptide Micro-Array Fabrication: Physicochemical and Assay Characteristics
Molecules 2013, 18(8), 9833-9849; doi:10.3390/molecules18089833
Received: 1 July 2013 / Revised: 25 July 2013 / Accepted: 6 August 2013 / Published: 16 August 2013
Cited by 11 | PDF Full-text (1150 KB) | HTML Full-text | XML Full-text
Abstract
Several azide-derivatized and fluorescently-labeled peptides were immobilized on azadibenzocyclooctyne (ADIBO)-activated slide surfaces via a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction revealing excellent immobilization kinetics, good spot homogeneities and reproducible fluorescence signal intensities. A myc-peptide micro-array immunoassay showed an antibody limit-of-detection (LOD) superior to
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Several azide-derivatized and fluorescently-labeled peptides were immobilized on azadibenzocyclooctyne (ADIBO)-activated slide surfaces via a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction revealing excellent immobilization kinetics, good spot homogeneities and reproducible fluorescence signal intensities. A myc-peptide micro-array immunoassay showed an antibody limit-of-detection (LOD) superior to a microtiter plate-based ELISA. Bovine serum albumin (BSA) and dextran covalently attached via “click” chemistry more efficiently reduced non-specific binding (NSB) of fluorescently-labeled IgG to the microarray surface in comparison to immobilized hexanoic acid and various types of polyethylene glycol (PEG) derivatives. Confirmation of these findings via further studies with other proteins and serum components could open up new possibilities for human sample and microarray platform-based molecular diagnostic tests. Full article
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Open AccessArticle Kinetics of Nitric Oxide and Oxygen Gases on Porous Y-Stabilized ZrO2-Based Sensors
Molecules 2013, 18(8), 9901-9918; doi:10.3390/molecules18089901
Received: 15 July 2013 / Revised: 8 August 2013 / Accepted: 13 August 2013 / Published: 16 August 2013
Cited by 4 | PDF Full-text (1926 KB) | HTML Full-text | XML Full-text
Abstract
Using impedance spectroscopy the electrical response of sensors with various porous Y-stabilized ZrO2 (YSZ) microstructures was measured for gas concentrations containing 0–100 ppm NO with 10.5%O2 at temperatures ranging from 600–700 °C. The impedance response increased substantially as the sensor porosity
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Using impedance spectroscopy the electrical response of sensors with various porous Y-stabilized ZrO2 (YSZ) microstructures was measured for gas concentrations containing 0–100 ppm NO with 10.5%O2 at temperatures ranging from 600–700 °C. The impedance response increased substantially as the sensor porosity increased from 46%–50%. Activation energies calculated based on data from the impedance measurements increased in magnitude (97.4–104.9 kJ/mol for 100 ppm NO) with respect to increasing YSZ porosity. Analysis of the oxygen partial pressure dependence of the sensors suggested that dissociative adsorption was the dominant rate limiting. The PWC/DNP theory level was used to investigate the gas-phase energy barrier of the 2NO+O2→2NO2 reaction on a 56-atom YSZ/Au model cluster using Density Functional Theory and Linear Synchronous Transit/Quadratic Synchronous Transit calculations. The reaction path shows oxygen surface reactions that begin with NO association with adsorbed O2 on a Zr surface site, followed by O2 dissociative adsorption, atomic oxygen diffusion, and further NO2 formation. The free energy barrier was calculated to be 181.7 kJ/mol at PWC/DNP. A qualitative comparison with the extrapolated data at 62% ± 2% porosity representing the YSZ model cluster indicates that the calculated barriers are in reasonable agreement with experiments, especially when the RPBE functional is used. Full article
(This article belongs to the Special Issue Gas Phase Reactions)
Open AccessArticle Chemistry and Antiviral Activity of Arrabidaea pulchra (Bignoniaceae)
Molecules 2013, 18(8), 9919-9932; doi:10.3390/molecules18089919
Received: 26 April 2013 / Revised: 22 July 2013 / Accepted: 24 July 2013 / Published: 16 August 2013
Cited by 7 | PDF Full-text (907 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present work was to carry out a bioguided isolation of antiviral chemical constituents from an ethanol extract of leaves from Arrabidaea pulchra (Cham.) Sandwith (EEAPL) that had shown in vitro activity in a previous screening using DNA and RNA
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The aim of the present work was to carry out a bioguided isolation of antiviral chemical constituents from an ethanol extract of leaves from Arrabidaea pulchra (Cham.) Sandwith (EEAPL) that had shown in vitro activity in a previous screening using DNA and RNA viruses. The activity of EEPAL was evaluated against the DNA viruses Human herpesvirus 1 (HSV-1) and Vaccinia virus Western Reserve (VACV-WR) as well as against the RNA viruses Murine encephalomyocarditis virus (EMCV), and Dengue virus 2 (DENV-2) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Cytotoxicity was determined in LLCMK2 and Vero cells and the Selectivity Indexes (SI) were calculated. The most potent effect was observed against DENV-2 (EC50 46.8 ± 1.6 µg mL−1; SI 2.7). For HSV-1 and VACV-WR EC50 values > 200 µg mL−1 were determined, while no inhibition of the cytopathic effect was observed with EMCV. Bioguided fractionation of EEAPL by partition between immiscible solvents followed by chromatography over a Sephadex LH20 column afforded two arylpropanoid glycosides, verbascoside (AP 1) and caffeoylcalleryanin (AP 2), along with a terpenoid, ursolic acid (AP 3). AP 1 and AP 3 exhibited similar anti-DENV-2 profiles, with SI values of 3.8 and 3.1, respectively, while AP 2 was the most effective anti-DENV-2 constituent, with a SI of 20.0. Our results show that A. pulchra leaves ethanol extract (EEAPL) affords compounds with antiviral activity, mainly against DENV-2. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Characterization and Bioactivity of Polysaccharides Obtained from Pine Cones of Pinus koraiensis by Graded Ethanol Precipitation
Molecules 2013, 18(8), 9933-9948; doi:10.3390/molecules18089933
Received: 8 June 2013 / Revised: 14 August 2013 / Accepted: 15 August 2013 / Published: 19 August 2013
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Abstract
Pinus koraiensis polysaccharides (PKP) were extracted by hot water from P. koraiensis pine cones. Five polysaccharide fractions named PKP-A, PKP-B, PKP-C, PKP-D and PKP-E were successfully separated at final ethanol concentrations of 30%, 50%, 60%, 70% and 80%, respectively. HPLC, FT-IR, GC-MS and
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Pinus koraiensis polysaccharides (PKP) were extracted by hot water from P. koraiensis pine cones. Five polysaccharide fractions named PKP-A, PKP-B, PKP-C, PKP-D and PKP-E were successfully separated at final ethanol concentrations of 30%, 50%, 60%, 70% and 80%, respectively. HPLC, FT-IR, GC-MS and automatic amino-acid analysis were applied to investigate their chemical characteristics. Monosaccharide component analysis indicated that the five fractions were all composed of d-ribose, l-rhamnose, l-arabinose, d-xylose, d-mannose, d-glucose and d-galactose, but their molar ratios were quite different. HPLC results revealed that the polysaccharides precipitated by higher concentrations of ethanol solution had lower molecular masses. Moreover, the antioxidant activities of the five fractions were studied on the basis of hydroxyl radical and ABTS radical scavenging tests. The five graded polysaccharide fractions exhibited good inhibitory power, and MTT tests in vitro showed the IC50 of PKP-A and PKP-E were 1,072.5 and 2,070.0 μg·mL−1, respectively. These results demonstrated that the PKP could be a potential source of natural antioxidants or dietary supplements. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model
Molecules 2013, 18(8), 9949-9965; doi:10.3390/molecules18089949
Received: 21 June 2013 / Revised: 31 July 2013 / Accepted: 6 August 2013 / Published: 19 August 2013
Cited by 32 | PDF Full-text (607 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ) are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a pharmacologically active agent.
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Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ) are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s) of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Lung Cancer Activity through Enhancement of Immunomodulation and Induction of Cell Apoptosis of Total Triterpenes Extracted from Ganoderma luncidum (Leyss. ex Fr.) Karst.
Molecules 2013, 18(8), 9966-9981; doi:10.3390/molecules18089966
Received: 14 June 2013 / Revised: 2 August 2013 / Accepted: 13 August 2013 / Published: 19 August 2013
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Abstract
Ganoderma luncidum (Leyss. ex Fr.) Karst. (GLK) has been used traditionally for the prevention and treatment of cancers or tumors for a long time in Traditional Chinese Medicine. The triterpenes as main effective components of GLK have been found to be beneficial for
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Ganoderma luncidum (Leyss. ex Fr.) Karst. (GLK) has been used traditionally for the prevention and treatment of cancers or tumors for a long time in Traditional Chinese Medicine. The triterpenes as main effective components of GLK have been found to be beneficial for the efficacy. The purpose of this study was to examine the anti-lung cancer activity of triterpenes of GLK in vitro and in vivo and to explore their anti-lung cancer effects and potential mechanisms. A549 cells and Lewis tumor-bearing mice were used to evaluate the inhibition effects of triterpenes on cell proliferation and tumor growth. The IC50 of triterpenes of GLK on A549 cells was 24.63 μg/mL. Triterpenes of GLK could significantly inhibit tumor growth in mice (30, 60 and 120 mg/kg). The immune organs indexes including spleen and thymus were increased remarkedly by the treatment with triterpenes. Moreover, they were able to stimulate the immune response by increasing the expressions of IL-6 and TNF-α. Flow cytometric analysis revealed that cell arrest caused by triterpenes treatment (7.5, 15 and 30 μg/mL) was in the G2/M phase in A549 cells. Triterpenes induced apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and pro-caspase 9 and increasing the levels of cleaved-caspase 9. Our findings suggested that the triterpenes of GLK have anti-lung cancer activity in vitro and in vivo via enhancement of immunomodulation and induction of cell apoptosis. The study provides insights into the mechanism of GLK in the prevention and treatment of lung cancer. Full article
Open AccessArticle Enantio- and Periselective Nitroalkene Diels-Alder Reactions Catalyzed by Helical-Chiral Hydrogen Bond Donor Catalysts
Molecules 2013, 18(8), 9982-9998; doi:10.3390/molecules18089982
Received: 15 July 2013 / Revised: 13 August 2013 / Accepted: 14 August 2013 / Published: 19 August 2013
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Abstract
Helical-chiral double hydrogen bond donor catalysts promote the nitroalkene Diels-Alder reaction in an enantio- and periselective manner. This represents the first asymmetric catalytic nitroalkene Diels-Alder reaction via LUMO-lowering catalysis. To gain an insight into this new process, the substrate scope of our catalyst
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Helical-chiral double hydrogen bond donor catalysts promote the nitroalkene Diels-Alder reaction in an enantio- and periselective manner. This represents the first asymmetric catalytic nitroalkene Diels-Alder reaction via LUMO-lowering catalysis. To gain an insight into this new process, the substrate scope of our catalyst was investigated by exploiting readily available 5-substituted pentamethylcyclopentadienes. The catalyst was found to tolerate dienes with different steric demands as well as dienes substituted with heteroatoms. The synthetic utility of 5-substituted pentamethylcyclopentadienes is rather limited, and thus we have developed a three-step route to 1,4,5,5-tetrasubstituted cyclopentadienes from commercially available ketones. Full article
(This article belongs to the Special Issue Asymmetric Catalysis)
Open AccessArticle Combination of Small Molecule Microarray and Confocal Microscopy Techniques for Live Cell Staining Fluorescent Dye Discovery
Molecules 2013, 18(8), 9999-10013; doi:10.3390/molecules18089999
Received: 26 June 2013 / Revised: 13 August 2013 / Accepted: 14 August 2013 / Published: 20 August 2013
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Abstract
Discovering new fluorochromes is significantly advanced by high-throughput screening (HTS) methods. In the present study a combination of small molecule microarray (SMM) prescreening and confocal laser scanning microscopy (CLSM) was developed in order to discover novel cell staining fluorescent dyes. Compounds with high
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Discovering new fluorochromes is significantly advanced by high-throughput screening (HTS) methods. In the present study a combination of small molecule microarray (SMM) prescreening and confocal laser scanning microscopy (CLSM) was developed in order to discover novel cell staining fluorescent dyes. Compounds with high native fluorescence were selected from a 14,585-member library and further tested on living cells under the microscope. Eleven compartment-specific, cell-permeable (or plasma membrane-targeted) fluorochromes were identified. Their cytotoxicity was tested and found that between 1–10 micromolar range, they were non-toxic even during long-term incubations. Full article
(This article belongs to the Special Issue Reagents and Methods for Protein Target Identification)
Open AccessArticle Antianxiety-Like Effects of Chimpi (Dried Citrus Peels) in the Elevated Open-Platform Test
Molecules 2013, 18(8), 10014-10023; doi:10.3390/molecules180810014
Received: 16 July 2013 / Revised: 9 August 2013 / Accepted: 16 August 2013 / Published: 20 August 2013
Cited by 6 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text
Abstract
Dried citrus peels (Chimpi) is one of the most common natural medicines with qi (energy flow) rectifying and shi (dampness) drying actions, which originates from Citrus unshiu, and/or C. reticulata according to the definition of the pharmacopoeiae of Japan and China.
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Dried citrus peels (Chimpi) is one of the most common natural medicines with qi (energy flow) rectifying and shi (dampness) drying actions, which originates from Citrus unshiu, and/or C. reticulata according to the definition of the pharmacopoeiae of Japan and China. In this study, the pharmacological effects of their extracts and major chemical constituents hesperidin and its aglycone hesperetin on anxiety were examined with an anxiety model of elevated open-platform test using ICR male mice (6-week-old) and total duration of freezing was decreased in fluoxetine-treated mice, which is a simple and highly sensitive to the effects of serotonergic anxiolytics. Moreover, yokukansankachimpihange (YKH), a combination of yokukansan with Chimpi and Hange (Pinellia) was also examined because Chimpi is considered to play a crucial part in this formula against anxious symptoms in dementia patients. The results showed that Chimpi and YKH possess a significant anxiolytic-like effect similar to that of fluoxetine, suggesting that they might be similar to fluoxetine in their pharmacological actions through the serotonergic neurotransmission pathway. Moreover, it also suggested that the major chemical constituent, hesperidin could be an active principle attributed to the antianxiety-like effects with a direct and indirect role via its aglycone hesperetin. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Volatile Aroma Compounds in Various Brewed Green Teas
Molecules 2013, 18(8), 10024-10041; doi:10.3390/molecules180810024
Received: 18 July 2013 / Revised: 7 August 2013 / Accepted: 14 August 2013 / Published: 20 August 2013
Cited by 14 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
This study identifies and semi-quantifies aroma volatiles in brewed green tea samples. The objectives of this study were to identify using a gas chromatograph-mass spectrometer (GC-MS) paired with a headspace solid-phase micro-extraction (HS-SPME) the common volatile compounds that may be responsible for aroma/flavor
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This study identifies and semi-quantifies aroma volatiles in brewed green tea samples. The objectives of this study were to identify using a gas chromatograph-mass spectrometer (GC-MS) paired with a headspace solid-phase micro-extraction (HS-SPME) the common volatile compounds that may be responsible for aroma/flavor of the brewed liquor of a range of green tea samples from various countries as consumed and to determine if green teas from the same region have similarities in volatile composition when green tea samples are prepared for consumption. Twenty-four green tea samples from eight different countries were brewed as recommended for consumer brewing. The aroma volatiles were extracted by HS-SPME, separated on a gas chromatograph and identified using a mass spectrometer. Thirty-eight compounds were identified and the concentrations were semi-quantified. The concentrations were lower than those reported by other researchers, probably because this research examined headspace volatiles from brewed tea rather than solvent extraction of leaves. No relationship to country of origin was found, which indicates that other factors have a greater influence than country of origin on aroma. Full article
(This article belongs to the Special Issue Flavors and Fragrances)
Open AccessCommunication Total Synthesis, Cytotoxic Effects of Damnacanthal, Nordamnacanthal and Related Anthraquinone Analogues
Molecules 2013, 18(8), 10042-10055; doi:10.3390/molecules180810042
Received: 22 May 2013 / Revised: 29 June 2013 / Accepted: 16 July 2013 / Published: 20 August 2013
Cited by 8 | PDF Full-text (317 KB) | HTML Full-text | XML Full-text
Abstract
Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ±
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Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ± 0.21 and 8.50 ± 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Modeling the Interaction of Dodecylphosphocholine Micelles with the Anticoccidial Peptide PW2 Guided by NMR Data
Molecules 2013, 18(8), 10056-10080; doi:10.3390/molecules180810056
Received: 19 July 2013 / Revised: 5 August 2013 / Accepted: 7 August 2013 / Published: 20 August 2013
Cited by 2 | PDF Full-text (1475 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antimicrobial peptides are highly dynamic entities that acquire structure upon binding to a membrane interface. To better understand the structure and the mechanism for the molecular recognition of dodecylphosphocholine (DPC) micelles by the anticoccidial peptide PW2, we performed molecular dynamics (MD) simulations guided
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Antimicrobial peptides are highly dynamic entities that acquire structure upon binding to a membrane interface. To better understand the structure and the mechanism for the molecular recognition of dodecylphosphocholine (DPC) micelles by the anticoccidial peptide PW2, we performed molecular dynamics (MD) simulations guided by NMR experimental data, focusing on strategies to explore the transient nature of micelles, which rearrange on a millisecond to second timescale. We simulated the association of PW2 with a pre-built DPC micelle and with free-DPC molecules that spontaneously forms micelles in the presence of the peptide along the simulation. The simulation with spontaneous micelle formation provided the adequate environment which replicated the experimental data. The unrestrained MD simulations reproduced the NMR structure for the entire 100 ns MD simulation time. Hidden discrete conformational states could be described. Coulomb interactions are important for initial approximation and hydrogen bonds for anchoring the aromatic region at the interface, being essential for the stabilization of the interaction. Arg9 is strongly attached with phosphate. We observed a helix elongation process stabilized by the intermolecular peptide-micelle association. Full association that mimics the experimental data only happens after complete micelle re-association. Fast micelle dynamics without dissociation of surfactants leads to only superficial binding. Full article
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Open AccessArticle Evaluation of Silica-H2SO4 as an Efficient Heterogeneous Catalyst for the Synthesis of Chalcones
Molecules 2013, 18(8), 10081-10094; doi:10.3390/molecules180810081
Received: 19 July 2013 / Revised: 5 August 2013 / Accepted: 7 August 2013 / Published: 20 August 2013
Cited by 8 | PDF Full-text (341 KB) | HTML Full-text | XML Full-text
Abstract
We report an efficient silica-H2SO4 mediated synthesis of a variety of chalcones that afforded the targeted compounds in very good yield compared to base catalyzed solvent free conditions as well as acid or base catalyzed refluxing conditions. Full article

Review

Jump to: Research

Open AccessReview Cytotoxic Activity of Ursolic Acid Derivatives Obtained by Isolation and Oxidative Derivatization
Molecules 2013, 18(8), 8929-8944; doi:10.3390/molecules18088929
Received: 14 June 2013 / Revised: 22 July 2013 / Accepted: 24 July 2013 / Published: 26 July 2013
Cited by 10 | PDF Full-text (610 KB) | HTML Full-text | XML Full-text
Abstract
Structure-activity relationships of ursane-type pentacyclic triterpenes obtained from natural sources and by chemical derivatization are reviewed. Ursolic acid, corosolic acid, and a new ursane-type pentacyclic triterpene, 7,24-dihydroxyursolic acid, were isolated from the methanolic extract of the leaves of the Bangladeshi medicinal plant, Saurauja
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Structure-activity relationships of ursane-type pentacyclic triterpenes obtained from natural sources and by chemical derivatization are reviewed. Ursolic acid, corosolic acid, and a new ursane-type pentacyclic triterpene, 7,24-dihydroxyursolic acid, were isolated from the methanolic extract of the leaves of the Bangladeshi medicinal plant, Saurauja roxburghii. Derivatization of ursolic acid by oxidation with dioxoruthenium (VI) tetraphenylporphyrins was investigated. Oxidation selectivity on the terpene structure was modulated by the auxiliaries introduced on the tetraphenylporphyrin. The natural triterpenes and oxidized derivatives were tested for cytotoxicity against the C6 rat glioma and A431 human skin carcinoma cell lines. Although they have the same ursane-type pentacyclic triterpene cores, the position and numbers of hydroxyls on the terpene structures significantly affected the activity and the selectivity towards the tested cell lines. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Marrubiin
Molecules 2013, 18(8), 9049-9060; doi:10.3390/molecules18089049
Received: 25 June 2013 / Revised: 20 July 2013 / Accepted: 22 July 2013 / Published: 29 July 2013
Cited by 8 | PDF Full-text (222 KB) | HTML Full-text | XML Full-text
Abstract
The ethno-medicinal approach to drug discovery represents one of the most important sources of new and safe therapeutic agents to the challenges confronting modern medicine and daily life. Many of the traditionally important medicinal plants contain active molecules or ones that serve as
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The ethno-medicinal approach to drug discovery represents one of the most important sources of new and safe therapeutic agents to the challenges confronting modern medicine and daily life. Many of the traditionally important medicinal plants contain active molecules or ones that serve as precursors to biosynthesised secondary metabolites to which the biological activity could be attributed. Marrubiin is one such compound and is a potential valuable compound which exists in high concentrations in many traditionally important Lamiaceae species which have demonstrated excellent pharmacological properties with commendably high safety margins. Marrubiin’s attributes include a low turnover, high stability and little catabolism, which are core characteristics required for therapeutic compounds and nutraceuticals of economic importance. In addition, marrubiin is considered a potential substrate for potent active compounds viz; marrubiinic acid, and marrubenol. The contribution of marrubiin to drug discovery thus needs to be put into prospective due to its ready availability, high potential applications and ease of modification. In this short review we highlight the most important chemical and pharmacological aspects reported on marrubiin since it was discovered. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads
Molecules 2013, 18(8), 9219-9240; doi:10.3390/molecules18089219
Received: 2 July 2013 / Revised: 14 July 2013 / Accepted: 18 July 2013 / Published: 2 August 2013
Cited by 14 | PDF Full-text (291 KB) | HTML Full-text | XML Full-text
Abstract
Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans
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Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria. Full article
(This article belongs to the Section Natural Products)
Open AccessReview Contributions of NMR to the Understanding of the Coordination Chemistry and DNA Interactions of Metallo-Bleomycins
Molecules 2013, 18(8), 9253-9277; doi:10.3390/molecules18089253
Received: 6 June 2013 / Revised: 27 July 2013 / Accepted: 29 July 2013 / Published: 2 August 2013
Cited by 1 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bleomycins are a family of glycopeptide antibiotics that have the ability to bind and degrade DNA when bound to key metal ions, which is believed to be responsible for their antitumor activity. Knowledge of the structures of metallo-bleomycins is vital to further characterize
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Bleomycins are a family of glycopeptide antibiotics that have the ability to bind and degrade DNA when bound to key metal ions, which is believed to be responsible for their antitumor activity. Knowledge of the structures of metallo-bleomycins is vital to further characterize their mechanism of action. To this end, numerous structural studies on metallo-bleomycins have been conducted. NMR spectroscopy has had a key role in most of these studies, and has led to very important findings involving the coordination chemistry of metallo-bleomycins, and the details of many metallo-bleomycin-DNA spatial correlations for this important drug. This paper reviews the most important contributions of NMR to the bleomycin field. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessReview Advances in Kinetic Isotope Effect Measurement Techniques for Enzyme Mechanism Study
Molecules 2013, 18(8), 9278-9292; doi:10.3390/molecules18089278
Received: 18 June 2013 / Revised: 22 July 2013 / Accepted: 29 July 2013 / Published: 2 August 2013
Cited by 3 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text
Abstract
Kinetic isotope effects (KIEs) are a very powerful tool for investigating enzyme mechanisms. Precision of measurement is the most important factor for KIE determinations, especially for small heavy atom KIEs. Internal competition is commonly used to measure small KIEs on V/K. Several methods,
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Kinetic isotope effects (KIEs) are a very powerful tool for investigating enzyme mechanisms. Precision of measurement is the most important factor for KIE determinations, especially for small heavy atom KIEs. Internal competition is commonly used to measure small KIEs on V/K. Several methods, including such as liquid scintillation counting, mass spectrometry, nuclear magnetic resonance spectroscopy and polarimetry have been used to determine KIEs. In this paper, which does not aspire to be an exhaustive review, we briefly review different experimental approaches for the measurement of KIEs on enzymatic reaction with an emphasis on newer techniques employing mass spectrometry and nuclear magnetic resonance spectrometry as well as some corresponding examples. Full article
(This article belongs to the Special Issue Isotope Effects)
Open AccessReview Strategies for Optimizing Water-Exchange Rates of Lanthanide-Based Contrast Agents for Magnetic Resonance Imaging
Molecules 2013, 18(8), 9352-9381; doi:10.3390/molecules18089352
Received: 19 June 2013 / Revised: 28 July 2013 / Accepted: 31 July 2013 / Published: 5 August 2013
Cited by 21 | PDF Full-text (519 KB) | HTML Full-text | XML Full-text
Abstract
This review describes recent advances in strategies for tuning the water-exchange rates of contrast agents for magnetic resonance imaging (MRI). Water-exchange rates play a critical role in determining the efficiency of contrast agents; consequently, optimization of water-exchange rates, among other parameters, is necessary
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This review describes recent advances in strategies for tuning the water-exchange rates of contrast agents for magnetic resonance imaging (MRI). Water-exchange rates play a critical role in determining the efficiency of contrast agents; consequently, optimization of water-exchange rates, among other parameters, is necessary to achieve high efficiencies. This need has resulted in extensive research efforts to modulate water-exchange rates by chemically altering the coordination environments of the metal complexes that function as contrast agents. The focus of this review is coordination-chemistry-based strategies used to tune the water-exchange rates of lanthanide(III)-based contrast agents for MRI. Emphasis will be given to results published in the 21st century, as well as implications of these strategies on the design of contrast agents. Full article
(This article belongs to the Special Issue Contrast Agents)
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Open AccessReview Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy
Molecules 2013, 18(8), 9451-9476; doi:10.3390/molecules18089451
Received: 27 June 2013 / Revised: 1 August 2013 / Accepted: 5 August 2013 / Published: 7 August 2013
Cited by 14 | PDF Full-text (1315 KB) | HTML Full-text | XML Full-text
Abstract
The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies
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The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs) and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process whereby most α-helical motifs are replaced by β-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal domain region of PrPC and cause spontaneous conversion to PrPSc. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify “hot spots” in PrPC involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrPC epitopes thought to be involved in modulating prion susceptibility. Here we present a detailed overview of our solution-state NMR studies on human prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research. Full article
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Open AccessReview The Click Reaction as an Efficient Tool for the Construction of Macrocyclic Structures
Molecules 2013, 18(8), 9512-9530; doi:10.3390/molecules18089512
Received: 1 July 2013 / Revised: 1 August 2013 / Accepted: 2 August 2013 / Published: 8 August 2013
Cited by 44 | PDF Full-text (418 KB) | HTML Full-text | XML Full-text
Abstract
The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click reaction) is an established tool used for the construction of complex molecular architectures. Given its efficiency it has been widely applied for bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has been utilized
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The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click reaction) is an established tool used for the construction of complex molecular architectures. Given its efficiency it has been widely applied for bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has been utilized for the efficient formation of rigid or shape-persistent, preorganized macrocyclic species. This strategy also allows the installment of useful functionalities, in the form of polar and function-rich 1,2,3-triazole moieties, directly embedded in the macrocyclic structures. This review analyzes the state of the art in this context, and provides some elements of perspective for future applications. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessReview Alkyne-Azide “Click” Chemistry in Designing Nanocarriers for Applications in Biology
Molecules 2013, 18(8), 9531-9549; doi:10.3390/molecules18089531
Received: 1 July 2013 / Revised: 3 August 2013 / Accepted: 5 August 2013 / Published: 8 August 2013
Cited by 34 | PDF Full-text (1424 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The alkyne-azide cycloaddition, popularly known as the “click” reaction, has been extensively exploited in molecule/macromolecule build-up, and has offered tremendous potential in the design of nanomaterials for applications in a diverse range of disciplines, including biology. Some advantageous characteristics of this coupling include
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The alkyne-azide cycloaddition, popularly known as the “click” reaction, has been extensively exploited in molecule/macromolecule build-up, and has offered tremendous potential in the design of nanomaterials for applications in a diverse range of disciplines, including biology. Some advantageous characteristics of this coupling include high efficiency, and adaptability to the environment in which the desired covalent linking of the alkyne and azide terminated moieties needs to be carried out. The efficient delivery of active pharmaceutical agents to specific organelles, employing nanocarriers developed through the use of “click” chemistry, constitutes a continuing topical area of research. In this review, we highlight important contributions click chemistry has made in the design of macromolecule-based nanomaterials for therapeutic intervention in mitochondria and lipid droplets. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
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Open AccessReview Ring Expansion of Vinylaziridines through the Strain-Release Pericyclic Reaction: Recent Developments and Applications
Molecules 2013, 18(8), 9650-9662; doi:10.3390/molecules18089650
Received: 23 July 2013 / Revised: 1 August 2013 / Accepted: 7 August 2013 / Published: 12 August 2013
Cited by 5 | PDF Full-text (612 KB) | HTML Full-text | XML Full-text
Abstract
Recent syntheses of azetidines, pyrrolidines, piperidines and azepines through cycloaddition or sigmatropic rearrangements of vinylaziridines are described. Applications to natural product synthesis and mechanistic investigations are also summarized. Full article
(This article belongs to the Special Issue Bioorthogonal Chemistry)
Open AccessReview The Emerging Role of Ferumoxytol-Enhanced MRI in the Management of Cerebrovascular Lesions
Molecules 2013, 18(8), 9670-9683; doi:10.3390/molecules18089670
Received: 14 June 2013 / Accepted: 8 August 2013 / Published: 13 August 2013
Cited by 13 | PDF Full-text (410 KB) | HTML Full-text | XML Full-text
Abstract
Inflammation is increasingly being understood to be a key component to the pathophysiology of cerebrovascular lesions. Ferumoxytol, an iron oxide nanoparticle coated by a carbohydrate shell, has been used in MRI studies as an inflammatory marker because it is cleared by macrophages. Ferumoxytol-enhanced
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Inflammation is increasingly being understood to be a key component to the pathophysiology of cerebrovascular lesions. Ferumoxytol, an iron oxide nanoparticle coated by a carbohydrate shell, has been used in MRI studies as an inflammatory marker because it is cleared by macrophages. Ferumoxytol-enhanced MRI has emerged as an important tool for noninvasive assessment of the inflammatory status of cerebrovascular lesions, namely aneurysms and arteriovenous malformations. Moreover, preliminary evidence suggests that ferumoxytol-enhanced MRI could be applied as a non-invasive tool to differentiate “unstable” lesions that require early intervention from “stable” lesions in which observation may be safe. Assessment of the effects of anti-inflammatory pharmacological interventions on cerebrovascular lesions is also a potentially crucial application of the technique. Future improvements in technique and MRI signal quantification will certainly pave the way for widespread and efficient use of ferumoxytol-enhanced MRI in clinical practice. In this paper, we review current data regarding ferumoxytol-enhanced MRI and discuss its current/potential applications and future perspectives. Full article
(This article belongs to the Special Issue Contrast Agents)
Open AccessReview Click Chemistry in Peptide-Based Drug Design
Molecules 2013, 18(8), 9797-9817; doi:10.3390/molecules18089797
Received: 15 July 2013 / Revised: 9 August 2013 / Accepted: 12 August 2013 / Published: 16 August 2013
Cited by 40 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text
Abstract
Click chemistry is an efficient and chemoselective synthetic method for coupling molecular fragments under mild reaction conditions. Since the advent in 2001 of methods to improve stereochemical conservation, the click chemistry approach has been broadly used to construct diverse chemotypes in both chemical
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Click chemistry is an efficient and chemoselective synthetic method for coupling molecular fragments under mild reaction conditions. Since the advent in 2001 of methods to improve stereochemical conservation, the click chemistry approach has been broadly used to construct diverse chemotypes in both chemical and biological fields. In this review, we discuss the application of click chemistry in peptide-based drug design. We highlight how triazoles formed by click reactions have been used for mimicking peptide and disulfide bonds, building secondary structural components of peptides, linking functional groups together, and bioconjugation. The progress made in this field opens the way for synthetic approaches to convert peptides with promising functional leads into structure-minimized and more stable forms. Full article
(This article belongs to the Special Issue Advances in Click Chemistry)
Open AccessReview Breathing Some New Life into an Old Topic: Chalcogen-Nitrogen π-Heterocycles as Electron Acceptors
Molecules 2013, 18(8), 9850-9900; doi:10.3390/molecules18089850
Received: 3 July 2013 / Revised: 13 August 2013 / Accepted: 14 August 2013 / Published: 16 August 2013
Cited by 34 | PDF Full-text (2445 KB) | HTML Full-text | XML Full-text
Abstract
Recent progress in the design, synthesis and characterization of chalcogen-nitrogen π-heterocycles, mostly 1,2,5-chalcogenadiazoles (chalcogen: S, Se and Te) and their fused derivatives, possessing positive electron affinity is discussed together with their use in preparation of charge-transfer complexes and radical-anion salts—candidate building blocks of
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Recent progress in the design, synthesis and characterization of chalcogen-nitrogen π-heterocycles, mostly 1,2,5-chalcogenadiazoles (chalcogen: S, Se and Te) and their fused derivatives, possessing positive electron affinity is discussed together with their use in preparation of charge-transfer complexes and radical-anion salts—candidate building blocks of molecule-based electrical and magnetic functional materials. Full article
(This article belongs to the Special Issue Chalcogen-Nitrogen Chemistry)
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