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Molecules, Volume 22, Issue 5 (May 2017)

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Cover Story The fluorescent chemical probe PDI-1 was designed for strong binding and quantification of [...] Read more.
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Editorial

Jump to: Research, Review

Open AccessEditorial Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes
Molecules 2017, 22(5), 743; doi:10.3390/molecules22050743
Received: 27 April 2017 / Revised: 27 April 2017 / Accepted: 27 April 2017 / Published: 5 May 2017
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(This article belongs to the Section Medicinal Chemistry)
Open AccessEditorial Special Issue: Ribozymes and RNA Catalysis
Molecules 2017, 22(5), 789; doi:10.3390/molecules22050789
Received: 9 May 2017 / Revised: 9 May 2017 / Accepted: 11 May 2017 / Published: 11 May 2017
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Abstract
Over the past 35 years, RNA has become a molecule of utmost interest for researchers in the life sciences. The many functions that RNA fulfills in the cellular machinery have been elucidated with constant progress, revealing a complex network of RNA-mediated regulation of
[...] Read more.
Over the past 35 years, RNA has become a molecule of utmost interest for researchers in the life sciences. The many functions that RNA fulfills in the cellular machinery have been elucidated with constant progress, revealing a complex network of RNA-mediated regulation of key processes in the cellular life cycle [...]
Full article
(This article belongs to the Special Issue Ribozymes and RNA Catalysis)
Open AccessEditorial Special Issue “Structure–Activity Relationship of Natural Products”
Molecules 2017, 22(5), 697; doi:10.3390/molecules22050697
Received: 25 April 2017 / Revised: 25 April 2017 / Accepted: 26 April 2017 / Published: 27 April 2017
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(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

Research

Jump to: Editorial, Review

Open AccessArticle The Hypnotic, Anxiolytic, and Antinociceptive Profile of a Novel µ-Opioid Agonist
Molecules 2017, 22(5), 800; doi:10.3390/molecules22050800
Received: 10 March 2017 / Revised: 17 April 2017 / Accepted: 26 April 2017 / Published: 16 May 2017
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Abstract
5′-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 112 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal
[...] Read more.
5′-4-Alkyl/aryl-1H-1,2,3-triazole derivatives PILAB 112 were synthesized and a pharmacological screening of these derivatives was performed to identify a possible effect on the Central Nervous System (CNS) and to explore the associated mechanisms of action. The mice received a peritoneal injection (100 µmol/kg) of each of the 12 PILAB derivatives 10 min prior to the injection of pentobarbital and the mean hypnosis times were recorded. The mean hypnosis time increased for the mice treated with PILAB 8, which was prevented when mice were administered CTOP, a µ-opioid antagonist. Locomotor and motor activities were not affected by PILAB 8. The anxiolytic effect of PILAB 8 was evaluated next in an elevated-plus maze apparatus. PILAB 8 and midazolam increased a percentage of entries and spent time in the open arms of the apparatus compared with the control group. Conversely, a decrease in the percentages of entries and time spent in the closed arms were observed. Pretreatment with naloxone, a non-specific opioid antagonist, prior to administration of PILAB 8 exhibited a reverted anxiolytic effect. PILAB 8 exhibited antinociceptive activity in the hot plate test, and reduced reactivity to formalin in the neurogenic and the inflammatory phases. These data suggest that PILAB 8 can activate µ-opioid receptors to provoke antinociceptive and anti-inflammatory effects in mice. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Formulation, Characterization and Properties of Hemp Seed Oil and Its Emulsions
Molecules 2017, 22(5), 700; doi:10.3390/molecules22050700
Received: 9 March 2017 / Revised: 13 April 2017 / Accepted: 25 April 2017 / Published: 27 April 2017
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Abstract
The formulation, characterization, and anticipated antibacterial properties of hemp seed oil and its emulsions were investigated. The oil obtained from the seeds of Cannabis sativa L. in refined and unrefined form was characterized using iodine, saponification, acid values, and gas chromatography, and was
[...] Read more.
The formulation, characterization, and anticipated antibacterial properties of hemp seed oil and its emulsions were investigated. The oil obtained from the seeds of Cannabis sativa L. in refined and unrefined form was characterized using iodine, saponification, acid values, and gas chromatography, and was employed for the preparation of stable oil-in-water emulsions. The emulsions were prepared using pairs of non-ionic surfactants (Tween, Span). The effects of the emulsification method (spontaneous emulsification vs. high-intensity stirring), hydrophilic lipophilic balance (HLB), type and concentration of surfactant, and oil type on the size and distribution of the emulsion particles were investigated. It was found that the ability to form stable emulsions with small, initial particle sizes is primarily dependent on the given method of preparation and the HLB value. The most efficient method of emulsification that afforded the best emulsions with the smallest particles (151 ± 1 nm) comprised the high-energy method, and emulsions stable over the long-term were observed at HBL 9 with 10 wt % concentration of surfactants. Under high-intensity emulsification, refined and unrefined oils performed similarly. The oils as well as their emulsions were tested against the growth of selected bacteria using the disk diffusion and broth microdilution methods. The antibacterial effect of hemp seed oil was documented against Micrococcus luteus and Staphylococcus aureus subsp. aureus. The formulated emulsions did not exhibit the antibacterial activity that had been anticipated. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Alcohols as Substrates and Solvents for the Construction of 3-Alkoxylated-2-Oxindoles by Direct Alkoxylation of 3-Halooxindoles
Molecules 2017, 22(5), 801; doi:10.3390/molecules22050801
Received: 20 April 2017 / Revised: 11 May 2017 / Accepted: 12 May 2017 / Published: 13 May 2017
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Abstract
Described herein is an environmentally benign method for the synthesis of multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3-halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil
[...] Read more.
Described herein is an environmentally benign method for the synthesis of multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3-halooxindoles 1. A wide variety of such multisubstituted 3-alkoxylated-2-oxindole scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil bath at 35 °C for 24 h. A particularly valuable feature of this method was the development of environment-friendly chemistry using alcohols 2 as both the substrates and solvents in the presence of a catalytic amount of base. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Silver Nanoparticles Mediated by Costus afer Leaf Extract: Synthesis, Antibacterial, Antioxidant and Electrochemical Properties
Molecules 2017, 22(5), 701; doi:10.3390/molecules22050701
Received: 10 March 2017 / Revised: 12 April 2017 / Accepted: 20 April 2017 / Published: 29 April 2017
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Abstract
Synthesis of metallic and semiconductor nanoparticles through physical and chemical routes has been extensively reported. However, green synthesized metal nanoparticles are currently in the limelight due to the simplicity, cost-effectiveness and eco-friendliness of their synthesis. This study explored the use of aqueous leaf
[...] Read more.
Synthesis of metallic and semiconductor nanoparticles through physical and chemical routes has been extensively reported. However, green synthesized metal nanoparticles are currently in the limelight due to the simplicity, cost-effectiveness and eco-friendliness of their synthesis. This study explored the use of aqueous leaf extract of Costus afer in the synthesis of silver nanoparticles (CA-AgNPs). The optical and structural properties of the resulting silver nanoparticles were studied using UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infra–red spectrophotometer (FTIR). TEM images of the silver nanoparticles confirmed the existence of monodispersed spherical nanoparticles with a mean size of 20 nm. The FTIR spectra affirmed the presence of phytochemicals from the Costus afer leaf extract on the surface of the silver nanoparticles. The electrochemical characterization of a CA-AgNPs/multiwalled carbon nanotubes (MWCNT)-modified electrode was carried out to confirm the charge transfer properties of the nanocomposites. The comparative study showed that the CA-AgNPs/MWCNT-modified electrode demonstrated faster charge transport behaviour. The anodic current density of the electrodes in Fe(CN)6]4−/[Fe(CN)6]3− redox probe follows the order: GCE/CA-Ag/MWCNT (550 mA/cm2) > GCE/MWCNT (270 mA/cm2) > GCE (80 mA/cm2) > GCE/CA-Ag (7.93 mA/cm2). The silver nanoparticles were evaluated for their antibacterial properties against Gram negative (Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa) and Gram positive (Bacillus subtilis and Staphylococcus aureus) pathogens. The nanoparticles exhibited better inhibition of the bacterial strains compared to the precursors (leaf extract of Costus afer and silver nitrate). Furthermore, the ability of the nanoparticles to scavenge DPPH radicals at different concentrations was studied using the DPPH radical scavenging assay and compared to that of the leaf extract and ascorbic acid. The nanoparticles were better DPPH scavengers compared to the leaf extract and their antioxidant properties compared favorably the antioxidant results of ascorbic acid. The green approach to nanoparticles synthesis carried out in this research work is simple, non-polluting, inexpensive and non-hazardous. Full article
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Open AccessArticle Protective Effect of Caffeic Acid Derivatives on tert-Butyl Hydroperoxide-Induced Oxidative Hepato-Toxicity and Mitochondrial Dysfunction in HepG2 Cells
Molecules 2017, 22(5), 702; doi:10.3390/molecules22050702
Received: 20 February 2017 / Revised: 19 April 2017 / Accepted: 25 April 2017 / Published: 28 April 2017
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Abstract
Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl
[...] Read more.
Oxidative stress results in structural and functional abnormalities in the liver and is thought to be a crucial factor in liver diseases. The aim of this study was to investigate the cytoprotective and antioxidant effects of caffeic acid (CA) derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Nine CA derivatives were synthesized, including N-phenylethyl caffeamide (PECA), N-(3-florophen)methyl caffeamide (FMCA), N-(4-methoxy-phen)methyl caffeamide (MPMCA), N-heptyl caffeamide (HCA), N-octyl caffeamide (OCA), octyl caffeate (CAOE), phenpropyl caffeate (CAPPE), phenethyl caffeate (CAPE), and phenmethyl caffeate (CAPME). The results showed that CA and its derivatives significantly inhibited t-BHP-induced cell death of HepG2 cells. The rank order of potency of the CA derivatives for cytoprotection was CAOE > HCA > OCA > FMCA > CAPPE > CAPME > CAPE > PECA > MPMCA > CA. Their cytoprotective activity was associated with lipophilicity. The antioxidant effect of these compounds was supported by the reduction in the levels of thiobarbituric acid reactive substrates, a biomarker of lipid peroxidation, in HepG2 cells. Pre-treatment of CA derivatives significantly prevented the depletion of glutathione, the most important water-soluble antioxidant in hepatocytes. Pre-treatment of CA derivatives before t-BHP exposure maintained mitochondrial oxygen consumption rate and ATP content in the injured HepG2 cells. CA derivatives except OCA and HCA significantly suppressed t-BHP-induced hypoxia-inducible factor-1α (HIF-1α) protein level. In addition, all of these CA derivatives markedly increased the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation in the nucleus, indicating that their cytoprotection may be mediated by the activation of Nrf2. Our results suggest that CA derivatives might be a hepatoprotective agent against oxidative stress. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I)
Molecules 2017, 22(5), 802; doi:10.3390/molecules22050802
Received: 22 March 2017 / Revised: 5 May 2017 / Accepted: 8 May 2017 / Published: 14 May 2017
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Abstract
The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as
[...] Read more.
The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I). Full article
(This article belongs to the Special Issue Women in Organic Chemistry)
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Open AccessArticle Chemical Composition, Antioxidant and α-Glucosidase-Inhibiting Activities of the Aqueous and Hydroethanolic Extracts of Vaccinium myrtillus Leaves
Molecules 2017, 22(5), 703; doi:10.3390/molecules22050703
Received: 30 January 2017 / Revised: 25 April 2017 / Accepted: 26 April 2017 / Published: 28 April 2017
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Abstract
Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was
[...] Read more.
Vaccinium myrtillus (bilberry) leaf is traditionally used in southeastern Europe for the treatment of diabetes. In the present study, the ability of bilberry leaf extracts to inhibit carbohydrate-hydrolyzing enzymes and restore glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress was investigated. A comprehensive analysis of the antioxidant activity of two bilberry leaf extracts was performed. The aqueous extract showed excellent total antioxidant and chelating activity. Its antioxidant activity in the β-carotene-linoleic acid assay was very good, reaching the activity of the antioxidant standard BHA (93.4 ± 2.3% vs. 95.1 ± 2.4%, respectively). The hydroethanolic extract (ethanol/H2O, 8:2, v/v), on the other hand, was a better radical scavenger and Fe2+ reducing agent. Furthermore, the aqueous extract was able to efficiently increase glutathione concentration in Hep G2 cells subjected to glucose-induced oxidative stress and restore it to the levels observed in non-hyperglycaemic cells. The hydroethanolic extract strongly inhibited α-glucosidase, with the IC50 statistically equal to the antidiabetic drug acarbose (0.29 ± 0.02 mg/mL vs. 0.50 ± 0.01 mg/mL, respectively). Phytochemical analysis revealed the presence of quercetin and kaemferol derivatives, as well as chlorogenic and p-coumaric acid. The study results indicate that V. myrtillus leaf may have promising properties as a supporting therapy for diabetes. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
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Open AccessArticle Effects of Mead Wort Heat Treatment on the Mead Fermentation Process and Antioxidant Activity
Molecules 2017, 22(5), 803; doi:10.3390/molecules22050803
Received: 5 April 2017 / Revised: 9 May 2017 / Accepted: 11 May 2017 / Published: 14 May 2017
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Abstract
The effects of mead wort heat treatment on the mead fermentation process and antioxidant activity were tested. The experiment was conducted with the use of two different honeys (multiflorous and honeydew) collected from the Lower Silesia region (Poland). Heat treatment was performed with
[...] Read more.
The effects of mead wort heat treatment on the mead fermentation process and antioxidant activity were tested. The experiment was conducted with the use of two different honeys (multiflorous and honeydew) collected from the Lower Silesia region (Poland). Heat treatment was performed with the use of a traditional technique (gently boiling), the more commonly used pasteurization, and without heat treatment (control). During the experiment fermentation dynamics were monitored using high performance liquid chromatography with refractive index detection (HPLC-RID). Total antioxidant capacity (TAC) and total phenolic content (TPC) were estimated for worts and meads using UV/Vis spectrophotometric analysis. The formation of 5-hydroxymethylfurfural (HMF) was monitored by HPLC analyses. Heat treatment had a great impact on the final antioxidant capacity of meads. Full article
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Open AccessArticle Evaluation of Efficient and Practical Methods for the Preparation of Functionalized Aliphatic Trifluoromethyl Ethers
Molecules 2017, 22(5), 804; doi:10.3390/molecules22050804
Received: 28 April 2017 / Revised: 11 May 2017 / Accepted: 11 May 2017 / Published: 14 May 2017
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Abstract The “chlorination/fluorination” technique for aliphatic trifluoromethyl ether synthesis was investigated and a range of products with various functional groups was prepared. The results were compared with oxidative desulfurization-fluorination of xanthates with the same structure. Full article
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Open AccessArticle Electrochemical Enhancement of Photocatalytic Disinfection on Aligned TiO2 and Nitrogen Doped TiO2 Nanotubes
Molecules 2017, 22(5), 704; doi:10.3390/molecules22050704
Received: 17 February 2017 / Revised: 24 April 2017 / Accepted: 26 April 2017 / Published: 28 April 2017
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Abstract
TiO2 photocatalysis is considered as an alternative to conventional disinfection processes for the inactivation of waterborne microorganisms. The efficiency of photocatalysis is limited by charge carrier recombination rates. When the photocatalyst is immobilized on an electrically conducting support, one may assist charge
[...] Read more.
TiO2 photocatalysis is considered as an alternative to conventional disinfection processes for the inactivation of waterborne microorganisms. The efficiency of photocatalysis is limited by charge carrier recombination rates. When the photocatalyst is immobilized on an electrically conducting support, one may assist charge separation by the application of an external electrical bias. The aim of this work was to study electrochemically assisted photocatalysis with nitrogen doped titania photoanodes under visible and UV-visible irradiation for the inactivation of Escherichia coli. Aligned TiO2 nanotubes were synthesized (TiO2-NT) by anodizing Ti foil. Nanoparticulate titania films were made on Ti foil by electrophoretic coating (P25 TiO2). N-doped titania nanotubes and N,F co-doped titania films were also prepared with the aim of extending the active spectrum into the visible. Electrochemically assisted photocatalysis gave higher disinfection efficiency in comparison to photocatalysis (electrode at open circuit) for all materials tested. It is proposed that electrostatic attraction of negatively charged bacteria to the positively biased photoanodes leads to the enhancement observed. The N-doped TiO2 nanotube electrode gave the most efficient electrochemically assisted photocatalytic inactivation of bacteria under UV-Vis irradiation but no inactivation of bacteria was observed under visible only irradiation. The visible light photocurrent was only a fraction (2%) of the UV response. Full article
(This article belongs to the Special Issue Photon-involving Purification of Water and Air)
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Open AccessArticle Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening Marker by Liquid Chromatography Tandem-mass Spectrometry
Molecules 2017, 22(5), 805; doi:10.3390/molecules22050805
Received: 4 March 2017 / Revised: 8 May 2017 / Accepted: 11 May 2017 / Published: 14 May 2017
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Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of
[...] Read more.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of RA prescreening. e identified differentially expressed proteins (DEPs) by using liquid chromatography tandem-mass spectrometry in health-prescreening sera with high rheumatoid factor (RF) values, and compared the findings with those from sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated, and 57 were downregulated in high-RF sera. Pathway analysis revealed that these DEPs were related to immune responses. Additionally, four DEPs were statistically analyzed by proteomic analysis; of these, SAA4 was significantly validated in individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly upregulated in RA patients (n = 40, 66.43 ± 12.97 ng/mL) compared with normal controls (n = 40, 4.79 ± 0.95 ng/mL) and had a higher area under the curve than C-reactive protein. Thus, we identified SAA4 as a protein that was positively correlated with RF and RA. SAA4 may represent a novel prescreening marker for the diagnosis of RA. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Generation and Applications of a DNA Aptamer against Gremlin-1
Molecules 2017, 22(5), 706; doi:10.3390/molecules22050706
Received: 16 March 2017 / Revised: 15 April 2017 / Accepted: 22 April 2017 / Published: 28 April 2017
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Abstract
Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein, plays important roles in diverse biological processes including early embryonic development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which are RNA or DNA single-stranded oligonucleotides capable of binding specifically to different targets ranging from small
[...] Read more.
Gremlin-1, a highly conserved glycosylated and phosphorylated secretory protein, plays important roles in diverse biological processes including early embryonic development, fibrosis, tumorigenesis, and renal pathophysiology. Aptamers, which are RNA or DNA single-stranded oligonucleotides capable of binding specifically to different targets ranging from small organics to whole cells, have potential applications in targeted imaging, diagnosis and therapy. In this study, we obtained a DNA aptamer against Gremlin-1 (G-ap49) using in vitro Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Binding assay and dot-blot showed that G-ap49 had high affinity for Gremlin-1. Further experiments indicated that G-ap49 was quite stable in a cell culture system and could be used in South-Western blot analysis, enzyme-linked aptamer sorbent assay (ELASA), and aptamer-based cytochemistry and histochemistry staining to detect Gremlin-1. Moreover, our study demonstrated that G-ap49 is capable of revealing the subcellular localization of Gremlin-1. These data indicate that G-ap49 can be used as an alternative to antibodies in detecting Gremlin-1. Full article
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
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Open AccessArticle Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors
Molecules 2017, 22(5), 806; doi:10.3390/molecules22050806
Received: 3 May 2017 / Accepted: 11 May 2017 / Published: 15 May 2017
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Abstract
Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue
[...] Read more.
Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity. Full article
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Open AccessArticle Isolaurenidificin and Bromlaurenidificin, Two New C15-Acetogenins from the Red Alga Laurencia obtusa
Molecules 2017, 22(5), 807; doi:10.3390/molecules22050807
Received: 15 April 2017 / Revised: 10 May 2017 / Accepted: 10 May 2017 / Published: 15 May 2017
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Abstract
Chromatographic fractionation of the CH2Cl2/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C15-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based
[...] Read more.
Chromatographic fractionation of the CH2Cl2/MeOH extract of the Red Sea red alga Laurencia obtusa gave two new hexahydrofuro[3,2-b]furan-based C15-acetogenins, namely, isolaurenidificin (1) and bromlaurenidificin (2). The chemical structures were elucidated based on extensive analyses of their spectral data. Compounds 1 and 2 showed no toxicity (LC50 > 12 mM) using Artemia salina as test organism. Both compounds showed weak cytotoxicity against A549, HepG-2, HCT116, MCF-7, and PC-3 cells, however, they exhibited a relatively potent cytotoxic activity against peripheral blood neutrophils. This can be attributed partly to induction of apoptosis. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle The Transcriptome of Type I Murine Astrocytes under Interferon-Gamma Exposure and Remyelination Stimulus
Molecules 2017, 22(5), 808; doi:10.3390/molecules22050808
Received: 24 March 2017 / Revised: 30 April 2017 / Accepted: 11 May 2017 / Published: 15 May 2017
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Abstract
Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report
[...] Read more.
Astrocytes are considered to be an important contributor to central nervous system (CNS) disorders, particularly multiple sclerosis. The transcriptome of these cells is greatly affected by cytokines released by lymphocytes, penetrating the blood–brain barrier—in particular, the classical pro-inflammatory cytokine interferon-gamma (IFNγ). We report here the transcriptomal profiling of astrocytes treated using IFNγ and benztropine, a putative remyelinization agent. Our findings indicate that the expression of genes involved in antigen processing and presentation in astrocytes are significantly upregulated upon IFNγ exposure, emphasizing the critical role of this cytokine in the redirection of immune response towards self-antigens. Data reported herein support previous observations that the IFNγ-induced JAK-STAT signaling pathway may be regarded as a valuable target for pharmaceutical interventions. Full article
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Open AccessFeature PaperArticle Selenium Speciation in the Fountain Creek Watershed (Colorado, USA) Correlates with Water Hardness, Ca and Mg Levels
Molecules 2017, 22(5), 708; doi:10.3390/molecules22050708
Received: 4 March 2017 / Revised: 14 April 2017 / Accepted: 19 April 2017 / Published: 30 April 2017
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Abstract
The environmental levels of selenium (Se) are regulated and strictly enforced by the Environmental Protection Agency (EPA) because of the toxicity that Se can exert at high levels. However, speciation plays an important role in the overall toxicity of Se, and only when
[...] Read more.
The environmental levels of selenium (Se) are regulated and strictly enforced by the Environmental Protection Agency (EPA) because of the toxicity that Se can exert at high levels. However, speciation plays an important role in the overall toxicity of Se, and only when speciation analysis has been conducted will a detailed understanding of the system be possible. In the following, we carried out the speciation analysis of the creek waters in three of the main tributaries—Upper Fountain Creek, Monument Creek and Lower Fountain Creek—located in the Fountain Creek Watershed (Colorado, USA). There are statistically significant differences between the Se, Ca and Mg, levels in each of the tributaries and seasonal swings in Se, Ca and Mg levels have been observed. There are also statistically significant differences between the Se levels when grouped by Pierre Shale type. These factors are considered when determining the forms of Se present and analyzing their chemistry using the reported thermodynamic relationships considering Ca2+, Mg2+, SeO42−, SeO32− and carbonates. This analysis demonstrated that the correlation between Se and water hardness can be explained in terms of formation of soluble CaSeO4. The speciation analysis demonstrated that for the Fountain Creek waters, the Ca2+ ion may be mainly responsible for the observed correlation with the Se level. Considering that the Mg2+ level is also correlating linearly with the Se levels it is important to recognize that without Mg2+ the Ca2+ would be significantly reduced. The major role of Mg2+ is thus to raise the Ca2+ levels despite the equilibria with carbonate and other anions that would otherwise decrease Ca2+ levels. Full article
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Open AccessArticle Multi-Anti-Parasitic Activity of Arylidene Ketones and Thiazolidene Hydrazines against Trypanosoma cruzi and Leishmania spp.
Molecules 2017, 22(5), 709; doi:10.3390/molecules22050709
Received: 21 March 2017 / Revised: 23 April 2017 / Accepted: 25 April 2017 / Published: 7 May 2017
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Abstract
A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to
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A series of fifty arylideneketones and thiazolidenehydrazines was evaluated against Leishmania infantum and Leishmania braziliensis. Furthermore, new simplified thiazolidenehydrazine derivatives were evaluated against Trypanosoma cruzi. The cytotoxicity of the active compounds on non-infected fibroblasts or macrophages was established in vitro to evaluate the selectivity of their anti-parasitic effects. Seven thiazolidenehydrazine derivatives and ten arylideneketones had good activity against the three parasites. The IC50 values for T. cruzi and Leishmania spp. ranged from 90 nM–25 µM. Eight compounds had multi-trypanocidal activity against T. cruzi and Leishmania spp. (the etiological agents of cutaneous and visceral forms). The selectivity of these active compounds was better than the three reference drugs: benznidazole, glucantime and miltefosine. They also had low toxicity when tested in vivo on zebrafish. Trying to understand the mechanism of action of these compounds, two possible molecular targets were investigated: triosephosphate isomerase and cruzipain. We also used a molecular stripping approach to elucidate the minimal structural requirements for their anti-T. cruzi activity. Full article
(This article belongs to the Special Issue Polypharmacology and Multitarget Drug Discovery)
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Open AccessArticle Mitochondria Targeting with Luminescent Rhenium(I) Complexes
Molecules 2017, 22(5), 809; doi:10.3390/molecules22050809
Received: 19 April 2017 / Revised: 10 May 2017 / Accepted: 11 May 2017 / Published: 15 May 2017
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Abstract
Two new neutral fac-[Re(CO)3(phen)L] compounds (1,2), with phen = 1,10-phenanthroline and L = O2C(CH2)5CH3 or O2C(CH2)4C≡CH, were synthetized in one-pot procedures from fac
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Two new neutral fac-[Re(CO)3(phen)L] compounds (1,2), with phen = 1,10-phenanthroline and L = O2C(CH2)5CH3 or O2C(CH2)4C≡CH, were synthetized in one-pot procedures from fac-[Re(CO)3(phen)Cl] and the corresponding carboxylic acids, and were fully characterized by IR and UV-Vis absorption spectroscopy, 1H- and 13C-NMR, mass spectrometry and X-ray crystallography. The compounds, which display orange luminescence, were used as probes for living cancer HeLa cell staining. Confocal microscopy revealed accumulation of both dyes in mitochondria. To investigate the mechanism of mitochondrial staining, a new non-emissive compound, fac-[Re(CO)3(phen)L], with L = O2C(CH2)3((C5H5)Fe(C5H4), i.e., containing a ferrocenyl moiety, was synthetized and characterized (3). 3 shows the same mitochondrial accumulation pattern as 1 and 2. Emission of 3 can only be possible when ferrocene-containing ligand dissociates from the metal center to produce a species containing the luminescent fac­[Re(CO)3(phen)]+ core. The release of ligands from the Re center was verified in vitro through the conjugation with model proteins. These findings suggest that the mitochondria accumulation of compounds 13 is due to the formation of luminescent fac-[Re(CO)3(phen)]+ products, which react with cellular matrix molecules giving secondary products and are uptaken into the negatively charged mitochondrial membranes. Thus, reported compounds feature a rare dissociation-driven mechanism of action with great potential for biological applications. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities
Molecules 2017, 22(5), 710; doi:10.3390/molecules22050710
Received: 14 April 2017 / Revised: 27 April 2017 / Accepted: 27 April 2017 / Published: 29 April 2017
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Abstract
A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidates 7ae and 4-arylmethyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidates 8ae were prepared via the reaction of N-(adamantan-1-yl)morpholine-4-carbothioamide 5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide 6 with benzyl or
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A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidates 7ae and 4-arylmethyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidates 8ae were prepared via the reaction of N-(adamantan-1-yl)morpholine-4-carbothioamide 5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide 6 with benzyl or substituted benzyl bromides, in acetone, in the presence of anhydrous potassium carbonate. The structures of the synthesized compounds were confirmed by 1H-NMR, 13C-NMR, electrospray ionization mass spectral (ESI-MS) data, and X-ray crystallographic data. The in vitro antimicrobial activity of the new compounds was determined against certain standard strains of pathogenic bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 7b, 7d and 7e displayed potent broad-spectrum antibacterial activity, while compounds 7a, 7c, 8b, 8d and 8e were active against the tested Gram-positive bacteria. The in vivo oral hypoglycemic activity of the new compounds was carried on streptozotocin (STZ)-induced diabetic rats. Compounds 7a, 8ab, and 8b produced potent dose-independent reduction of serum glucose levels, compared to the potent hypoglycemic drug gliclazide. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration
Molecules 2017, 22(5), 810; doi:10.3390/molecules22050810
Received: 13 April 2017 / Revised: 10 May 2017 / Accepted: 11 May 2017 / Published: 17 May 2017
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Abstract
Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (2D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify
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Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (2D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC0−∞) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them. Full article
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Open AccessArticle MALDI-MS Imaging of Urushiols in Poison Ivy Stem
Molecules 2017, 22(5), 711; doi:10.3390/molecules22050711
Received: 30 March 2017 / Revised: 24 April 2017 / Accepted: 26 April 2017 / Published: 29 April 2017
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Abstract
Urushiols are the allergenic components of Toxicodendron radicans (poison ivy) as well as other Toxicodendron species. They are alk-(en)-yl catechol derivatives with a 15- or 17-carbon side chain having different degrees of unsaturation. Although several methods have been developed for analysis of urushiols
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Urushiols are the allergenic components of Toxicodendron radicans (poison ivy) as well as other Toxicodendron species. They are alk-(en)-yl catechol derivatives with a 15- or 17-carbon side chain having different degrees of unsaturation. Although several methods have been developed for analysis of urushiols in plant tissues, the in situ localization of the different urushiol congeners has not been reported. Here, we report on the first analysis of urushiols in poison ivy stems by matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). Our results show that the urushiol congeners with 15-carbon side chains are mainly localized to the resin ducts, while those with 17-carbon side chains are widely distributed in cortex and vascular tissues. The presence of these urushiols in stem extracts of poison ivy seedlings was confirmed by GC-MS. These novel findings provide new insights into the spatial tissue distribution of urushiols that might be biosynthetically or functionally relevant. Full article
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Open AccessArticle The Phenolic Fraction of Mentha haplocalyx and Its Constituent Linarin Ameliorate Inflammatory Response through Inactivation of NF-κB and MAPKs in Lipopolysaccharide-Induced RAW264.7 Cells
Molecules 2017, 22(5), 811; doi:10.3390/molecules22050811
Received: 15 March 2017 / Revised: 1 May 2017 / Accepted: 9 May 2017 / Published: 16 May 2017
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Abstract
Mentha haplocalyx has been widely used for its flavoring and medicinal properties and as a traditional Chinese medicine with its anti-inflammation properties. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of the phenolic fraction of M. haplocalyx
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Mentha haplocalyx has been widely used for its flavoring and medicinal properties and as a traditional Chinese medicine with its anti-inflammation properties. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of the phenolic fraction of M. haplocalyx (MHP) and its constituent linarin in lipopolysaccharide (LPS)-induced RAW264.7 cells. The high-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ-Orbitrap MS) was used to analyze the chemical composition of MHP. Using the enzyme-linked immunosorbent assay (ELISA) and quantitative realtime polymerase chain reaction (qRT-PCR), the expression of pro-inflammatory meditators and cytokines was measured at the transcriptional and translational levels. Western blot analysis was used to further investigate changes in the nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Akt signaling pathways. Fourteen phenolic constituents were identified from MHP based on the data of the mass spectrometry (MS)/MS analysis. MHP and linarin decreased the production of NO, tumor necrosis factor-α (TNF-α), interlenkin-1β (IL-1β), and IL-6. The messenger ribonucleic acid (mRNA) expression levels of inducible NO synthase (iNOS), TNF-α, IL-1β, and IL-6 were also suppressed by MHP and linarin. Further investigation showed that MHP and linarin down-regulated LPS-induced phosphorylation content of NF-κB p65, inhibitor kappa B α (IκBα), extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. However, MHP and linarin showed no inhibitory effect on the phosphorylated Akt. These results suggested that MHP and linarin exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of NF-κB and MAPKs, and they may serve as potential modulatory agents for the prevention and treatment of inflammatory diseases. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle 4-Hydroxy-7-methyl-3-phenylcoumarin Suppresses Aflatoxin Biosynthesis via Downregulation of aflK Expressing Versicolorin B Synthase in Aspergillus flavus
Molecules 2017, 22(5), 712; doi:10.3390/molecules22050712
Received: 17 December 2016 / Revised: 26 April 2017 / Accepted: 27 April 2017 / Published: 29 April 2017
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Abstract
Naturally occurring coumarins possess antibacterial and antifungal properties. In this study, these natural and synthetic coumarins were used to evaluate their antifungal activities against Aspergillus flavus, which produces aflatoxins. In addition to control antifungal activities, antiaflatoxigenic properties were also determined using a
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Naturally occurring coumarins possess antibacterial and antifungal properties. In this study, these natural and synthetic coumarins were used to evaluate their antifungal activities against Aspergillus flavus, which produces aflatoxins. In addition to control antifungal activities, antiaflatoxigenic properties were also determined using a high-performance liquid chromatography in conjunction with fluorescence detection. In this study, 38 compounds tested and 4-hydroxy-7-methyl-3-phenyl coumarin showed potent antifungal and antiaflatoxigenic activities against A. flavus. Inhibitory mode of antiaflatoxigenic action by 4-hydroxy-7-methyl-3-phenyl coumarin was based on the downregulation of aflD, aflK, aflQ, and aflR in aflatoxin biosynthesis. In the cases of coumarins, antifungal and aflatoxigenic activities are highly related to the lack of diene moieties in the structures. In structurally related compounds, 2,3-dihydrobenzofuran exhibited antifungal and antiaflatoxigenic activities against A. flavus. The inhibitory mode of antiaflatoxigenic action by 2,3-dihydrobenzofuran was based on the inhibition of the transcription factor (aflS) in the aflatoxin biosynthesis pathway. These potent inhibitions of 2,3-dihydrobenzofuran and 4-hydroxy-7-methyl-3-phenyl coumarin on the Aspergillus growth and production of aflatoxins contribute to the development of new controlling agents to mitigate aflatoxin contamination. Full article
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Open AccessArticle Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives
Molecules 2017, 22(5), 812; doi:10.3390/molecules22050812
Received: 30 March 2017 / Revised: 5 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
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Abstract
Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in
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Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 ≤ 50 µM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Markers of Oxidative Stress and Antioxidant Defense in Romanian Patients with Type 2 Diabetes Mellitus and Obesity
Molecules 2017, 22(5), 714; doi:10.3390/molecules22050714
Received: 13 March 2017 / Revised: 14 April 2017 / Accepted: 26 April 2017 / Published: 1 May 2017
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Abstract
Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The
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Type 2 diabetes mellitus (T2DM) is strongly associated with obesity. The adipose tissue secretes bioactive adipokines leading to low grade inflammation, amplified by oxidative stress, which promotes the formation of advanced glycation end products and eventually leads to dyslipidemia and vascular complications. The aim of this study was to correlate anthropometric, biochemical and oxidative stress parameters in newly diagnosed (ND) T2DM patients and to investigate the role of oxidative stress in T2DM associated with obesity. A group of 115 ND- T2DM patients was compared to a group of 32 healthy subjects in terms of clinical, anthropometric, biochemical and oxidative stress parameters. ND-T2DM patients had significantly lower adiponectin, glutathione (GSH) and gluthatione peroxidase (GPx) and elevated insulin, proinsulin, HOMA-IR index, proinsulin/insulin (P/I) and proinsulin/adiponectin (P/A) ratio, fructosamine, and total oxidant status (TOS). The total body fat mass was positively correlated with total oxidant status (TOS). Positive correlations were found between TOS and glycated hemoglobin (HbA1c), and between TOS and glycaemia. Negative correlations were identified between: GPx and glycaemia, GPx and HbA1c, and also between GSH and fructosamine. The total antioxidant status was negatively correlated with the respiratory burst. The identified correlations suggest the existence of a complex interplay between diabetes, obesity and oxidative stress. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
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Open AccessArticle Optimization of EPS Production and Characterization by a Halophilic Bacterium, Kocuria rosea ZJUQH from Chaka Salt Lake with Response Surface Methodology
Molecules 2017, 22(5), 814; doi:10.3390/molecules22050814
Received: 18 April 2017 / Revised: 11 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
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Abstract
With the rising awareness of microbial exopolysaccharides (EPSs) application in various fields, halophilic microorganisms which produce EPSs have received broad attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined to be a moderate halobacterium on account of its successful adaption to
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With the rising awareness of microbial exopolysaccharides (EPSs) application in various fields, halophilic microorganisms which produce EPSs have received broad attention. A newly identified Kocuria rosea ZJUQH CCTCC M2016754 was determined to be a moderate halobacterium on account of its successful adaption to the environment containing 10% NaCl. The optimal combination of fermentation medium compositions on EPS production was studied. In this work, a fractional factorial design was adopted to investigate the significant factors that affected EPS production. The factors of KCl and MgSO4 were found to have a profound impact on EPS production. We utilized central composite design and response surface methodology to derive a statistical model for optimizing the submerged culture medium composition. Judging from these experimental results, the optimum culture medium for producing EPSs was composed of 0.50% casein hydrolysate, 1.00% sodium citrate, 0.30% yeast extract, 0.50% KCl, 0.50% peptone, and 5.80% MgSO4 (initial pH 7.0). The maximal EPS was 48.01 g/L, which is close to the predicted value (50.39 g/L). In the validation experiment, the highest concentration of 70.64 g/L EPSs was obtained after 120 h under the optimized culture medium in a 5-L bioreactor. EPS from this bacterium was also characterized by differential scanning calorimetry (DSC) and Fourier transform infrared analysis (FT-IR). The findings in this study imply that Kocuria rosea ZJUQH has great potential to be exploited as a source of EPSs utilized in food, the pharmaceutical and agriculture industry, and in the biotreatment of hypersaline environments. Full article
(This article belongs to the Special Issue Natural Polysaccharides)
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Open AccessArticle Anti-Inflammatory Effects, SAR, and Action Mechanism of Monoterpenoids from Radix Paeoniae Alba on LPS-Stimulated RAW 264.7 Cells
Molecules 2017, 22(5), 715; doi:10.3390/molecules22050715
Received: 29 March 2017 / Revised: 27 April 2017 / Accepted: 27 April 2017 / Published: 29 April 2017
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Abstract
Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous
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Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous phytochemistry investigations. Their anti-inflammatory effects were determined in the present study. The expression and production of pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells were measured using an Elisa assay and nitric oxide (NO) release was determined using the Griess method. The results demonstrated that the most of the monoterpenoids suppressed the LPS-induced production of NO, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The anti-inflammatory activities of these monoterpenoids were closely related to their structural characteristics. Paeoniflorins and paeonidanins presented stronger anti-inflammatory activities than those of albiflorin derivatives. Furthermore, the action mechanisms of MBPF, having a strong anti-inflammatory effect, were investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods. The results indicated that MBPF could down-regulate the mRNA and protein expression level of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells. The mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor κB (NF-κB) signaling pathways are involved in mediating the role of MBPF in suppressing the expression and production of pro-inflammatory cytokines in RAW 264.7 cells. Full article
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Open AccessArticle Leishmanicidal Activity and Structure-Activity Relationships of Essential Oil Constituents
Molecules 2017, 22(5), 815; doi:10.3390/molecules22050815
Received: 17 March 2017 / Revised: 9 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
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Abstract
Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene,
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Several constituents of essential oils have been shown to be active against pathogens such as bacteria, fungi, and protozoa. This study demonstrated the in vitro action of ten compounds present in essential oils against Leishmania amazonensis promastigotes. With the exception of p-cymene, all evaluated compounds presented leishmanicidal activity, exhibiting IC50 between 25.4 and 568.1 μg mL−1. Compounds with the best leishmanicidal activity presented a phenolic moiety (IC50 between 25.4 and 82.9 μg mL−1). Alicyclic alcohols ((−)-menthol and isoborneol) and ketones ((−)-carvone) promoted similar activity against the parasite (IC50 between 190.2 and 198.9 μg mL−1). Most of the compounds showed low cytotoxicity in L929 fibroblasts. Analysis of the structure-activity relationship of these compounds showed the importance of the phenolic structure for the biological action against the promastigote forms of the parasite. Full article
Open AccessFeature PaperArticle Volatile Composition in Two Pummelo Cultivars (Citrus grandis L. Osbeck) from Different Cultivation Regions in China
Molecules 2017, 22(5), 716; doi:10.3390/molecules22050716
Received: 5 March 2017 / Revised: 13 April 2017 / Accepted: 25 April 2017 / Published: 29 April 2017
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Abstract
This study investigated the composition of volatile compounds in two pummelo cultivars, including ‘Shatian’ and ‘Guanxi’, cultivated in different regions of China with the aim of studying the effect of cultivar and cultivation condition on biosynthesis of volatile compounds in pummelo. Volatile compounds
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This study investigated the composition of volatile compounds in two pummelo cultivars, including ‘Shatian’ and ‘Guanxi’, cultivated in different regions of China with the aim of studying the effect of cultivar and cultivation condition on biosynthesis of volatile compounds in pummelo. Volatile compounds were extracted from pummelo juice using head-space microextraction and then analyzed using gas chromatography coupled with mass spectrometry. Results showed that a total of 49 volatile compounds was detected in the study, including 11 aldehydes, 7 alcohols, 3 ketones, 7 esters, 19 terpenes and 2 other volatiles. The ‘Guanxi’ pummelo cultivar possessed a more complex composition of volatile compounds compared with the ‘Shatian’ cultivar. Meanwhile, the volatile compounds appeared to exhibit a higher concentration in the ‘Guanxi’ cultivar samples than the ‘Shatian’ cultivar. Cluster analysis revealed that the ‘Guanxi’ cultivar samples from the different regions were grouped together, whereas the ‘Shatian’ cultivar samples were assembled. Principal component analysis showed that an obvious separation was observed between the ‘Guanxi’ and ‘Shatian’ cultivar. However, the ‘Shatian-SC15’ was significantly separated from the other ‘Shatian’ cultivar samples. These indicated that cultivar genotype was the primary factor that determined the volatile profile of the pummelo cultivar. Cultivation region might affect the biosynthesis of volatile compounds, resulting in the differentiation of the volatile composition in each pummelo cultivar. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Cation, Anion and Ion-Pair Complexes with a G-3 Poly(ethylene imine) Dendrimer in Aqueous Solution
Molecules 2017, 22(5), 816; doi:10.3390/molecules22050816
Received: 12 April 2017 / Revised: 12 May 2017 / Accepted: 12 May 2017 / Published: 16 May 2017
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Abstract
The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability, being able to bind metal cations, anions and ion-pairs. The equilibrium constants for the formation of metal (Cu2+, Zn2+), anion (SO42−) and ion-pair (Cu2+
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The G-3 poly(ethylene imine) ligand L2 shows a multifaceted coordination ability, being able to bind metal cations, anions and ion-pairs. The equilibrium constants for the formation of metal (Cu2+, Zn2+), anion (SO42−) and ion-pair (Cu2+/SO42−) complexes were determined in 0.1 M Me4NCl aqueous solution at 298.1 ± 0.1 K by means of potentiometric titrations. Thanks to its dendrimeric nature, L2 can form highly nucleated metal complexes, such as Cu5L210+ and Zn4L28+, in successive and well-defined complexation steps. Protonated forms of L2 give rise to relatively weak anion complexes with SO42−, but the addition of Cu2+ significantly enhances the binding ability of the ligand toward this anion below pH 9. In more alkaline solutions, an opposite trend is observed. The coordination properties of L2 are discussed with the support of modelling calculations. According to results, L2 is a promising molecule for the preparation of solid supported materials for the recovery of cations and anions from aqueous media and/or for applications in heterogeneous catalysis. Full article
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Open AccessArticle Synthesis of Pyrimethanil-Loaded Mesoporous Silica Nanoparticles and Its Distribution and Dissipation in Cucumber Plants
Molecules 2017, 22(5), 817; doi:10.3390/molecules22050817
Received: 11 April 2017 / Revised: 9 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
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Abstract
Mesoporous silica nanoparticles are used as pesticide carries in plants, which has been considered as a novel method to reduce the indiscriminate use of conventional pesticides. In the present work, mesoporous silica nanoparticles with particle diameters of 200–300 nm were synthesized in order
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Mesoporous silica nanoparticles are used as pesticide carries in plants, which has been considered as a novel method to reduce the indiscriminate use of conventional pesticides. In the present work, mesoporous silica nanoparticles with particle diameters of 200–300 nm were synthesized in order to obtain pyrimethanil-loaded nanoparticles. The microstructure of the nanoparticles was observed by scanning electron microscopy. The loading content of pyrimethanil-loaded nanoparticles was investigated. After treatment on cucumber leaves, the concentrations of pyrimethanil were determined in different parts of cucumber over a period of 48 days using high performance liquid chromatography tandem mass spectrometry. It was shown that the pyrimethanil-loaded mesoporous silica nanoparticles might be more conducive to acropetal, rather than basipetal, uptake, and the dosage had almost no effect on the distribution and dissipation rate in cucumber plants. The application of the pesticide-loaded nanoparticles in leaves had a low risk of pyrimethanil accumulating in the edible part of the plant. Full article
(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)
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Open AccessArticle Chemical Comparison of Two Drying Methods of Mountain Cultivated Ginseng by UPLC-QTOF-MS/MS and Multivariate Statistical Analysis
Molecules 2017, 22(5), 717; doi:10.3390/molecules22050717
Received: 14 April 2017 / Revised: 26 April 2017 / Accepted: 27 April 2017 / Published: 30 April 2017
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Abstract
In traditional Chinese medicine practice, drying method is an essential factor to influence the components of Chinese medicinal herbs. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based approach was used to compare the content of chemical compounds of
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In traditional Chinese medicine practice, drying method is an essential factor to influence the components of Chinese medicinal herbs. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based approach was used to compare the content of chemical compounds of mountain cultivated ginseng that had been natural air dried (LX-P) and vacuum freeze-dried (LX-L). Multivariate statistical analysis such as principal component analysis (PCA) and supervised orthogonal partial least squared discrimination analysis (OPLS-DA) were used to select the influential components of different samples. There were 41 ginsenosides unambiguously identified and tentatively assigned in both LX-L and LX-P. The results showed that the characteristic components in LX-P were ginsenoside Rb1, ginsenoside Rc, ginsenoside Rg6, dendrolasin, and ginsenoside Rb2. The characteristic components in LX-L were malonyl-ginsenoside Re, malonyl-ginsenoside Rb1, malonyl-ginsenoside Rc, malonyl-ginsenoside Rb1 isomer, malonyl-ginsenoside Rb2, malonyl-ginsenoside Rb3, malonyl-ginsenoside Rd isomer, gypenoside XVII, and notoginsenoside Fe. This is the first time that the differences between LX-L and LX-P have been observed systematically at the chemistry level. It was indicated that vacuum freeze-drying method can improve the content of malonyl-ginsensides in mountain cultivated ginseng. Full article
(This article belongs to the Special Issue Current Trends in Ginseng Research)
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Open AccessArticle Supporting the Identification of Novel Fragment-Based Positive Allosteric Modulators Using a Supervised Molecular Dynamics Approach: A Retrospective Analysis Considering the Human A2A Adenosine Receptor as a Key Example
Molecules 2017, 22(5), 818; doi:10.3390/molecules22050818
Received: 9 March 2017 / Revised: 3 May 2017 / Accepted: 10 May 2017 / Published: 16 May 2017
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Abstract
Structure-driven fragment-based (SDFB) approaches have provided efficient methods for the identification of novel drug candidates. This strategy has been largely applied in discovering several pharmacological ligand classes, including enzyme inhibitors, receptor antagonists and, more recently, also allosteric (positive and negative) modulators. Recently, Siegal
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Structure-driven fragment-based (SDFB) approaches have provided efficient methods for the identification of novel drug candidates. This strategy has been largely applied in discovering several pharmacological ligand classes, including enzyme inhibitors, receptor antagonists and, more recently, also allosteric (positive and negative) modulators. Recently, Siegal and collaborators reported an interesting study, performed on a detergent-solubilized StaR adenosine A2A receptor, describing the existence of both fragment-like negative allosteric modulators (NAMs), and fragment-like positive allosteric modulators (PAMs). From this retrospective study, our results suggest that Supervised Molecular Dynamics (SuMD) simulations can support, on a reasonable time scale, the identification of fragment-like PAMs following their receptor recognition pathways and characterizing the possible allosteric binding sites. Full article
(This article belongs to the Special Issue Adenosine Receptors)
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Open AccessArticle Rapid Quantification and Quantitation of Alkaloids in Xinjiang Fritillaria by Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry
Molecules 2017, 22(5), 719; doi:10.3390/molecules22050719
Received: 20 March 2017 / Revised: 25 April 2017 / Accepted: 28 April 2017 / Published: 1 May 2017
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Abstract
The Fritillaria genus, including different kinds of medicinal and edible plants belonging to the Liliaceae family which have the function of treating and relieving a cough and eliminating phlegm, is widely planted in Xinjiang (China). There are few comprehensive studies reporting on the
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The Fritillaria genus, including different kinds of medicinal and edible plants belonging to the Liliaceae family which have the function of treating and relieving a cough and eliminating phlegm, is widely planted in Xinjiang (China). There are few comprehensive studies reporting on the characterization of the chemical constituents of Fritillaria from Xinjiang, and to date, no work describing the quantitative differences between the components in Fritillaria from Xinjiang and related species. The purpose of this study was to develop qualitative and quantitative analytical methods by Ultra Performance Liquid Chromatography-Quadrupole Time-of-flight Mass Spectrometry (UPLC-QTOF-MS) for the rapid quantification and quantitation of alkaloids in wild and cultivated Xinjiang Fritillaria, which could be used in the quality control of medicine based on this natural herb. Using the UPLC-QTOF-MS method, the chemical constituents of Xinjiang Fritillaria were identified by fragmentation information and retention behavior, and were compared to reference standards. Furthermore, a quantitative comparision of four major alkaloids in wild and cultivated Xinjiang Fritillaria was conducted by determining the content of Sipeimine-3β-d-glucoside, Sipeimine, Peimisine, and Yibeinoside A, respectively. A total of 89 characteristic peaks, including more than 40 alkaloids, were identified in the chromatographic results of Fritillaria. Four main alkaloids were quantified by using a validated method based on UPLC-QTOF-MS. The relative contents of Sipeimine-3β-d-glucoside, Sipeimine, Peimisine, and Yibeinoside A varied from 0.0013%~0.1357%, 0.0066%~0.1218%, 0.0033%~0.0437%, and 0.0019%~0.1398%, respectively. A rough separation of wild and cultivated Fritillaria could be achieved by the cluster analysis method. Full article
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Open AccessArticle Biomimetic Synthesis of Resveratrol Trimers Catalyzed by Horseradish Peroxidase
Molecules 2017, 22(5), 819; doi:10.3390/molecules22050819
Received: 31 March 2017 / Revised: 11 May 2017 / Accepted: 11 May 2017 / Published: 17 May 2017
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Abstract
Biotransformation of trans-resveratrol and synthetic (±)-ε-viniferin in aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants resulted in the isolation of two new resveratrol trimers (3 and 4), one new resveratrol derivative (5) with a dihydrobenzofuran skeleton,
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Biotransformation of trans-resveratrol and synthetic (±)-ε-viniferin in aqueous acetone using horseradish peroxidase and hydrogen peroxide as oxidants resulted in the isolation of two new resveratrol trimers (3 and 4), one new resveratrol derivative (5) with a dihydrobenzofuran skeleton, together with two known stilbene trimers (6 and 7), and six known stilbene dimers (813). Their structures and relative configurations were identified through spectral analysis and possible formation mechanisms were also discussed. Among these oligomers, trimers 6 and 7 were obtained for the first time through direct transformation from resveratrol. Results indicated that this reaction is suitable for the preparation of resveratrol oligomers with a complex structure. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and Mechanistic Study
Molecules 2017, 22(5), 820; doi:10.3390/molecules22050820
Received: 18 March 2017 / Revised: 11 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
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Abstract
A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions
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A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr3. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus involved Vilsmeier amidination, imination reactions, and the sequential intermolecular heterocyclization. To study the reaction mechanism, a series of 4-formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl-formamidine, were prepared and successfully converted into pyrazolo[3,4-d]pyrimidines. The experiments demonstrated that the reaction intermediates were the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl)formamidines. The rate of the reaction could be described as being proportional to the reactivity of amine reactants during intermolecular heterocyclization, especially when hexamethyldisilazane was used. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Toward Exploring Novel Organic Materials: MP4-DFT Properties of 4-Amino-3-Iminoindene
Molecules 2017, 22(5), 720; doi:10.3390/molecules22050720
Received: 8 March 2017 / Revised: 23 April 2017 / Accepted: 25 April 2017 / Published: 30 April 2017
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Abstract
Tautomerism links with many applications and remains an attracting feature in exploring novel systems. In this regard, properties of indene-based HNCCCN segments have not received any considerable attention. In this computational organic chemistry study, first, to calculate the proton transfer energy barrier at
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Tautomerism links with many applications and remains an attracting feature in exploring novel systems. In this regard, properties of indene-based HNCCCN segments have not received any considerable attention. In this computational organic chemistry study, first, to calculate the proton transfer energy barrier at a reasonable cost, the study identified an accurate forth order Møller–Plesset perturbation theory-density functional theory (MP4-DFT) protocol equivalent to the outstanding pioneering benchmark calculations. The calculations illustrate that the two tautomers of the 4-amino-3-iminoindene nucleus are separated by a considerable energy barrier while featuring different molecular orbital characteristics; frontier orbital distribution, λmax, and energies, which are known basic requirements in molecular switching and logic circuit applications. The N-H/BH2 substitution was found to have significant influence on the electronic structure of the skeleton. Similarities in the two tautomers and the boron derivative to properties of known molecular materials have been found. Full article
(This article belongs to the Section Theoretical Chemistry)
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Open AccessArticle From Cell to Beak: In-Vitro and In-Vivo Characterization of Chicken Bitter Taste Thresholds
Molecules 2017, 22(5), 821; doi:10.3390/molecules22050821
Received: 19 April 2017 / Revised: 12 May 2017 / Accepted: 12 May 2017 / Published: 17 May 2017
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Abstract
Bitter taste elicits an aversive reaction, and is believed to protect against consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein-coupled receptors, with a species-dependent number of subtypes. Chickens demonstrate bitter taste sensitivity despite having only three bitter taste receptors—ggTas2r1,
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Bitter taste elicits an aversive reaction, and is believed to protect against consuming poisons. Bitter molecules are detected by the Tas2r family of G-protein-coupled receptors, with a species-dependent number of subtypes. Chickens demonstrate bitter taste sensitivity despite having only three bitter taste receptors—ggTas2r1, ggTas2r2 and ggTas2r7. This minimalistic bitter taste system in chickens was used to determine relationships between in-vitro (measured in heterologous systems) and in-vivo (behavioral) detection thresholds. ggTas2r-selective ligands, nicotine (ggTas2r1), caffeine (ggTas2r2), erythromycin and (+)-catechin (ggTas2r7), and the Tas2r-promiscuous ligand quinine (all three ggTas2rs) were studied. Ligands of the same receptor had different in-vivo:in-vitro ratios, and the ggTas2r-promiscuous ligand did not exhibit lower in-vivo:in-vitro ratios than ggTas2r-selective ligands. In-vivo thresholds were similar or up to two orders of magnitude higher than the in-vitro ones. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle One-Step Synthesis of Silver Nanoparticles on Polydopamine-Coated Sericin/Polyvinyl Alcohol Composite Films for Potential Antimicrobial Applications
Molecules 2017, 22(5), 721; doi:10.3390/molecules22050721
Received: 25 March 2017 / Revised: 19 April 2017 / Accepted: 27 April 2017 / Published: 30 April 2017
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Abstract
Silk sericin has great potential as a biomaterial for biomedical applications due to its good hydrophilicity, reactivity, and biodegradability. To develop multifunctional sericin materials for potential antibacterial application, a one-step synthesis method for preparing silver nanoparticles (AgNPs) modified on polydopamine-coated sericin/polyvinyl alcohol (PVA)
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Silk sericin has great potential as a biomaterial for biomedical applications due to its good hydrophilicity, reactivity, and biodegradability. To develop multifunctional sericin materials for potential antibacterial application, a one-step synthesis method for preparing silver nanoparticles (AgNPs) modified on polydopamine-coated sericin/polyvinyl alcohol (PVA) composite films was developed. Polydopamine (PDA) acted as both metal ion chelating and reducing agent to synthesize AgNPs in situ on the sericin/PVA composite film. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed that polydopamine could effectively facilitate the high-density growth of AgNPs as a 3-D matrix. X-ray diffractometry studies suggested the synthesized AgNPs formed good face-centered cubic crystalline structures. Contact angle measurement and mechanical test indicated AgNPs modified PDA-sericin/PVA composite film had good hydrophilicity and mechanical property. The bacterial growth curve and inhibition zone assays showed the AgNPs modified PDA-sericin/PVA composite film had long-term antibacterial activities. This work develops a new method for the preparation of AgNPs modified PDA-sericin/PVA film with good hydrophilicity, mechanical performance and antibacterial activities for the potential antimicrobial application in biomedicine. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay
Molecules 2017, 22(5), 722; doi:10.3390/molecules22050722
Received: 20 March 2017 / Revised: 24 April 2017 / Accepted: 27 April 2017 / Published: 30 April 2017
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Abstract
For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral
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For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL−1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL−1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Rhodium(I)-Complexes Catalyzed 1,4-Conjugate Addition of Arylzinc Chlorides to N-Boc-4-pyridone
Molecules 2017, 22(5), 723; doi:10.3390/molecules22050723
Received: 15 March 2017 / Revised: 27 April 2017 / Accepted: 27 April 2017 / Published: 1 May 2017
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Abstract
Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C2H4)2]2 and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition
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Rhodium(I)-complexes catalyzed the 1,4-conjugate addition of arylzinc chlorides to N-Boc-4-pyridone in the presence of chlorotrimethylsilane (TMSCl). A combination of [RhCl(C2H4)2]2 and BINAP was determined to be the most effective catalyst to promote the 1,4-conjugate addition reactions of arylzinc chlorides to N-Boc-4-pyridone. A broad scope of arylzinc reagents with both electron-withdrawing and electron-donating substituents on the aromatic ring successfully underwent 1,4-conjugate addition to N-Boc-4-pyridone to afford versatile 1,4-adducts 2-substituted-2,3-dihydropyridones in good to excellent yields (up to 91%) and excellent ee (up to 96%) when (S)-BINAP was used as chiral ligand. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Antibacterial Activity of 7-Epiclusianone and Its Novel Copper Metal Complex on Streptococcus spp. Isolated from Bovine Mastitis and Their Cytotoxicity in MAC-T Cells
Molecules 2017, 22(5), 823; doi:10.3390/molecules22050823
Received: 23 March 2017 / Revised: 4 May 2017 / Accepted: 10 May 2017 / Published: 17 May 2017
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Abstract
Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia
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Mastitis is an inflammation of mammary gland parenchyma that adversely affects bovine health and dairy production worldwide despite significant efforts to eradicate it. The aim of this work was to characterize the antimicrobial activity of 7-epiclusianone (7-epi), a compound extracted from the Rheedia brasiliensis fruit, its complex with copper against Streptococcus spp. isolated from bovine mastitis, and to assess their cytotoxicity to bovine mammary alveolar cells (MAC-T). The complex 7-epiclusianone-Cu (7-epi-Cu) was an amorphous green solid with optical activity. Its vibrational spectrum in the infrared region showed absorption bands in the high-frequency region, as well as bands that can be attributed to the unconjugated and conjugated stretching of the free ligand. The complex was anhydrous. One of the tested bacterial strains was not sensitive to the compounds, while the other three had MIC values of 7.8 µg mL−1 and minimum bactericidal concentration (MBC) values between 15.6 and 31.3 µg mL−1. These two compounds are bacteriostatic, did not cause damage to the cell wall and, at sub-inhibitory concentrations, did not induce bacterial adhesion. The compounds were not cytotoxic. Based on these results, 7-epi and 7-epi-Cu exhibited desirable antimicrobial properties and could potentially be used in bovine mastitis treatment. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Effects of Growth Media on the Diversity of Culturable Fungi from Lichens
Molecules 2017, 22(5), 824; doi:10.3390/molecules22050824
Received: 1 March 2017 / Revised: 10 May 2017 / Accepted: 11 May 2017 / Published: 17 May 2017
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Abstract
Microscopic and molecular studies suggest that lichen symbioses contain a plethora of associated fungi. These are potential producers of novel bioactive compounds, but strains isolated on standard media usually represent only a minor subset of these fungi. By using various in vitro growth
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Microscopic and molecular studies suggest that lichen symbioses contain a plethora of associated fungi. These are potential producers of novel bioactive compounds, but strains isolated on standard media usually represent only a minor subset of these fungi. By using various in vitro growth conditions we are able to modulate and extend the fraction of culturable lichen-associated fungi. We observed that the presence of iron, glucose, magnesium and potassium in growth media is essential for the successful isolation of members from different taxonomic groups. According to sequence data, most isolates besides the lichen mycobionts belong to the classes Dothideomycetes and Eurotiomycetes. With our approach we can further explore the hidden fungal diversity in lichens to assist in the search of novel compounds. Full article
(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities)
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Open AccessArticle Detecting and Discriminating Shigella sonnei Using an Aptamer-Based Fluorescent Biosensor Platform
Molecules 2017, 22(5), 825; doi:10.3390/molecules22050825
Received: 19 April 2017 / Revised: 11 May 2017 / Accepted: 14 May 2017 / Published: 17 May 2017
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Abstract
In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate specific aptamers against Shigella sonnei. Real-time PCR amplification and post-SELEX experiment revealed that the selected aptmers possessed a high binding affinity and specificity for S. sonnei. Of the 21
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In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate specific aptamers against Shigella sonnei. Real-time PCR amplification and post-SELEX experiment revealed that the selected aptmers possessed a high binding affinity and specificity for S. sonnei. Of the 21 aptamers tested, the C(t) values of the SS-3 and SS-4 aptamers (Ct = 13.89 and Ct = 12.23, respectively) had the lowest value compared to other aptamer candidates. The SS-3 and SS-4 aptamers also displayed a binding affinity (KD) of 39.32 ± 5.02 nM and 15.89 ± 1.77 nM, respectively. An aptamer-based fluorescent biosensor assay was designed to detect and discriminate S. sonnei cells using a sandwich complex pair of SS-3 and SS-4. The detection of S. sonnei by the aptamer based fluorescent biosensor platform consisted of three elements: (1) 5’amine-SS-4 modification in a 96-well type microtiter plate surface (N-oxysuccinimide, NOS) as capture probes; (2) the incubation with S. sonnei and test microbes in functionalized 96 assay wells in parallel; (3) the readout of fluorescent activity using a Cy5-labeled SS-3 aptamer as the detector. Our platform showed a significant ability to detect and discriminate S. sonnei from other enteric species such as E. coli, Salmonella typhimurium and other Shigella species (S. flexneri, S. boydii). In this study, we demonstrated the feasibility of an aptamer sensor platform to detect S. sonnei in a variety of foods and pave the way for its use in diagnosing shigellosis through multiple, portable designs. Full article
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
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Open AccessArticle Quasi-Living Polymerization of Propene with an Isotactic-Specific Zirconocene Catalyst
Molecules 2017, 22(5), 725; doi:10.3390/molecules22050725
Received: 6 April 2017 / Revised: 24 April 2017 / Accepted: 27 April 2017 / Published: 2 May 2017
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Abstract
Propene polymerization with isotactic (iso)-specific C2-symmetric rac-Me2Si(2-Me-Benz(e)-Ind)2ZrCl2 (1) and rac-Me2Si(2-Me-4-Ph-1-Ind)2ZrCl2 (2) were conducted under various conditions for achieving iso-specific living polymerization of
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Propene polymerization with isotactic (iso)-specific C2-symmetric rac-Me2Si(2-Me-Benz(e)-Ind)2ZrCl2 (1) and rac-Me2Si(2-Me-4-Ph-1-Ind)2ZrCl2 (2) were conducted under various conditions for achieving iso-specific living polymerization of propene. When Complex 1 was activated with trialkylaluminum-free modified methylaluminoxane (dMMAO) at −40 °C, the number-average molecular weight (Mn) linearly increased against the polymerization time to reach Mn = 704,000 within 15 min of polymerization, although the molecular weight distributions was broad (Mw/Mn < 3). Thus, it was found that quasi-living polymerization of propene proceeded in the 1-dMMAO system. The living nature of iso-polypropene was confirmed by the block copolymerization, where the Mn value increased from 221,000 to 382,000 after the addition of 1-octene to yield the block copolymer with a melting point of 150 °C. Full article
(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)
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Open AccessArticle Effects of Copper Pollution on the Phenolic Compound Content, Color, and Antioxidant Activity of Wine
Molecules 2017, 22(5), 726; doi:10.3390/molecules22050726
Received: 12 February 2017 / Revised: 26 April 2017 / Accepted: 28 April 2017 / Published: 3 May 2017
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Abstract
The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased,
[...] Read more.
The effects of copper pollution on the polyphenol content, color, and antioxidant activity of wine, as well as correlations among these factors, were investigated. Copper had clear influences on wine polyphenol content. At low copper concentrations, the concentrations of nearly all polyphenols increased, and the antioxidant activity values of the wine also increased. When the copper concentration reached the lowest level of the medium copper range (9.6~16 mg/L), most of the indices also improved. When the copper concentrations reached the latter part of the medium copper range (19.2 and 22.4 mg/L), many of the tested indices began to decrease. Furthermore, when the copper concentration reached the high ranges (32, 64, and 96 mg/L), the polyphenol content, CIELAB color parameters, and antioxidant activity of wine were substantially decreased, indicating the need to control increasing copper content in grape must. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle Acetylcholinesterase Inhibitory Meroterpenoid from a Mangrove Endophytic Fungus Aspergillus sp. 16-5c
Molecules 2017, 22(5), 727; doi:10.3390/molecules22050727
Received: 12 April 2017 / Revised: 26 April 2017 / Accepted: 28 April 2017 / Published: 3 May 2017
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Abstract
One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2
[...] Read more.
One new meroterpenoid, named 2-hydroacetoxydehydroaustin (1), together with nine known meroterpenoids, 11-acetoxyisoaustinone (2), isoaustinol (3), austin (4), austinol (5), acetoxydehydroaustin (6), dehydroaustin (7), dehydroaustinol (8), preaustinoid A2 (9), and 1,2-dihydro-acetoxydehydroaustin B (10), were isolated from the mangrove endophytic fungus, Aspergillus sp. 16-5c. These structures were characterized by spectroscopic analysis, further the absolute configurations of stereogenic carbons for Compounds 1, 3, 4, 6, 7, 8, 9, and 10 were determined by single crystal X-ray diffraction analysis using Cu Kα radiation. Moreover, the absolute configurations of stereogenic carbons for Known Compounds 3, 7, 8, and 9 are identified here for the first time. Compounds 3, 7, and 8 showed acetylcholinesterase (AchE) inhibitory activity with IC50 values of 2.50, 0.40, and 3.00 μM, respectively. Full article
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Open AccessArticle Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products
Molecules 2017, 22(5), 827; doi:10.3390/molecules22050827
Received: 12 April 2017 / Revised: 11 May 2017 / Accepted: 12 May 2017 / Published: 18 May 2017
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Abstract
Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders
[...] Read more.
Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp3 character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp3 features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium. Full article
(This article belongs to the Special Issue Natural Product Inspired Scaffolds Designs)
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Open AccessArticle New Glycosides from the Fruits of Nicandra physaloides
Molecules 2017, 22(5), 828; doi:10.3390/molecules22050828
Received: 9 April 2017 / Revised: 16 May 2017 / Accepted: 16 May 2017 / Published: 17 May 2017
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Abstract
Three new glycosides (13) and 15 known ones (418) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS.
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Three new glycosides (13) and 15 known ones (418) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (418) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values from 26.9 to 47.5 μM. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle The Impact of the Low Molecular Weight Heparin Tinzaparin on the Sensitization of Cisplatin-Resistant Ovarian Cancers—Preclinical In Vivo Evaluation in Xenograft Tumor Models
Molecules 2017, 22(5), 728; doi:10.3390/molecules22050728
Received: 28 March 2017 / Revised: 26 April 2017 / Accepted: 28 April 2017 / Published: 3 May 2017
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Abstract
Resistance formation of tumors against chemotherapeutics is the major obstacle in clinical cancer therapy. Although low molecular weight heparin (LMWH) is an important component in oncology referring to guideline-based antithrombotic prophylaxis of tumor patients, a potential interference of LMWH with chemoresistance is unknown.
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Resistance formation of tumors against chemotherapeutics is the major obstacle in clinical cancer therapy. Although low molecular weight heparin (LMWH) is an important component in oncology referring to guideline-based antithrombotic prophylaxis of tumor patients, a potential interference of LMWH with chemoresistance is unknown. We have recently shown that LMWH reverses the cisplatin resistance of A2780cis human ovarian cancer cells in vitro. Here we address the question whether this LMWH effect is also valid under in vivo conditions. Therefore, we established tumor xenografts of A2780 and cisplatin resistant A2780cis cells in nude mice and investigated the impact of daily tinzaparin applications (10 mg/kg BW) on anti-tumor activity of cisplatin (6 mg/kg BW, weekly) considering the tumor growth kinetics. Intratumoral platinum accumulation was detected by GF-AAS. Xenografts of A2780 and A2780cis cells strongly differed in cisplatin sensitivity. As an overall consideration, tinzaparin co-treatment affected the response to cisplatin of A2780cis, but not A2780 tumors in the later experimental time range. A subgroup analysis confirmed that initially smaller A2780cis tumors benefit from tinzaparin, but also small A2780 xenografts. Tinzaparin did not affect cisplatin accumulation in A2780cis xenografts, but strongly increased the platinum content in A2780, obviously related to morphological differences in both xenografts. Although we cannot directly confirm a return of A2780cis cisplatin resistance by tinzaparin, as shown in vitro, the present findings give reason to discuss heparin effects on cytostatic drug efficiency for small tumors and warrants further investigation. Full article
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Open AccessArticle Microwave-Assisted Synthesis of Imidazo[4,5-f][1,10]phenanthroline Derivatives as Apoptosis Inducers in Chemotherapy by Stabilizing Bcl-2 G-quadruplex DNA
Molecules 2017, 22(5), 829; doi:10.3390/molecules22050829
Received: 23 March 2017 / Revised: 11 May 2017 / Accepted: 14 May 2017 / Published: 20 May 2017
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Abstract
Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO2, 1; CF3, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3–94.7% at
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Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO2, 1; CF3, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3–94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC50) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially 1, exhibited excellent inhibitory activity against the growth of A549 cells with IC50 of 15.03 μM. Moreover, it’s also confirmed that 1 can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that 1 can bind to bcl-2 G-quadruplex DNA, which demonstrated by the increase of melting point of bcl-2 G4 DNA in the presence of 1, as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to the bcl-2 G-quadruplex DNA. Full article
(This article belongs to the Special Issue ECSOC-20)
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Open AccessArticle Assessing Scaffold Diversity of Kinase Inhibitors Using Alternative Scaffold Concepts and Estimating the Scaffold Hopping Potential for Different Kinases
Molecules 2017, 22(5), 730; doi:10.3390/molecules22050730
Received: 13 April 2017 / Revised: 26 April 2017 / Accepted: 1 May 2017 / Published: 3 May 2017
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Abstract
Publicly available kinase inhibitors provide a large source of information for structure–activity relationship analysis and kinase drug design. In this study, publicly available inhibitors of the human kinome were collected and analog series formed by kinase inhibitors systematically identified. Then, alternative scaffold concepts
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Publicly available kinase inhibitors provide a large source of information for structure–activity relationship analysis and kinase drug design. In this study, publicly available inhibitors of the human kinome were collected and analog series formed by kinase inhibitors systematically identified. Then, alternative scaffold concepts were applied to assess diversity and promiscuity of kinase inhibitors. Over the past two years, the number of publicly available kinase inhibitors with high-confidence activity data more than doubled, but coverage of the human kinome only slightly increased. Approximately 70% of current kinase inhibitors belonged to analog series. However, the detectable degree of promiscuity among these kinase inhibitors remained low. Approximately 76% of all inhibitors were only annotated with a single kinase, compared to ~70% two years ago. For many kinases, the assessment of scaffold diversity among their inhibitors and the distribution of differently defined scaffolds over analog series made it possible to assess scaffold hopping potential. Our analysis revealed that the consideration of conventional compound-based scaffolds most likely leads to an overestimation of scaffold hopping frequency, at least for compounds forming analog series. Full article
(This article belongs to the Special Issue Kinase Inhibitors)
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Open AccessArticle Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice
Molecules 2017, 22(5), 830; doi:10.3390/molecules22050830
Received: 11 April 2017 / Revised: 11 May 2017 / Accepted: 15 May 2017 / Published: 18 May 2017
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Abstract
An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with
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An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1β, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Template Effect of the Graphene Moiré Lattice on Phthalocyanine Assembly
Molecules 2017, 22(5), 731; doi:10.3390/molecules22050731
Received: 21 March 2017 / Revised: 27 April 2017 / Accepted: 28 April 2017 / Published: 3 May 2017
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Abstract
Superstructures of metal-free phthalocyanine (2H-Pc) molecules on graphene-covered Ir(111) have been explored by scanning tunnelling microscopy. Depending on the sub-monolayer coverage different molecular assemblies form at the surface. They reflect the transition from a graphene template effect on the 2H-Pc arrangement to molecular
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Superstructures of metal-free phthalocyanine (2H-Pc) molecules on graphene-covered Ir(111) have been explored by scanning tunnelling microscopy. Depending on the sub-monolayer coverage different molecular assemblies form at the surface. They reflect the transition from a graphene template effect on the 2H-Pc arrangement to molecular superstructures that are mainly governed by the intermolecular coupling. Full article
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Open AccessArticle Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2
Molecules 2017, 22(5), 732; doi:10.3390/molecules22050732
Received: 7 March 2017 / Revised: 25 April 2017 / Accepted: 28 April 2017 / Published: 4 May 2017
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Abstract
Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic
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Brazilian green propolis (BGP) is noted for its impressive antitumor effects and has been used as a folk medicine in various cultures for many years. It has been demonstrated that BGP could enhance the cytotoxic effect of cytostatic drugs on tumor cells. Photodynamic therapy (PDT) is a therapeutic approach used against malignant cells. To assess the synergistic effect of BGP extract on protoporphyrin IX (PpIX)-mediated photocytotoxicity, MTT assays were performed using A431 and HeLa cells. TUNEL assay and Annexin V-FITC/PI staining were performed to confirm the induction of apoptosis. Western blotting analysis was performed to examine the pro-apoptotic proteins, anti-apoptotic proteins and inflammation related proteins in A431 cells. Intracellular accumulation of PpIX was examined by flow cytometry. The synergistic effect of BGP extract in PpIX-PDT was also evaluated with a xenograft model. Our findings reveal that BGP extract increased PpIX-mediated photocytotoxicity in A431 and HeLa cells. PpIX-PDT with BGP extract treatment resulted in a decrease in Bcl-xL and an increase in NOXA, Bax and caspase-3 cleavage. The protein expression levels of p-IKKα/β, NF-κB and COX-2 were upregulated by PpIX-PDT but significantly attenuated when in combination with BGP extract. BGP extract was also found to significantly enhance the intracellular accumulation of PpIX in A431 cells. BGP extract increased PpIX-mediated photocytotoxicity in a xenograft model as well. Our findings provide evidence for a synergistic effect of BGP extract in PpIX-PDT both in vitro and in vivo. Full article
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Open AccessArticle In Vitro Assessment of Early Bacterial Activity on Micro/Nanostructured Ti6Al4V Surfaces
Molecules 2017, 22(5), 832; doi:10.3390/molecules22050832
Received: 29 March 2017 / Revised: 13 May 2017 / Accepted: 16 May 2017 / Published: 18 May 2017
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Abstract
It is imperative to understand and systematically compare the initial interactions between bacteria genre and surface properties. Thus, we fabricated a flat, anodized with 80 nm TiO2 nanotubes (NTs), and a rough Ti6Al4V surface. The materials were characterized using field-emission scanning electron
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It is imperative to understand and systematically compare the initial interactions between bacteria genre and surface properties. Thus, we fabricated a flat, anodized with 80 nm TiO2 nanotubes (NTs), and a rough Ti6Al4V surface. The materials were characterized using field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM). We cultured in vitro Staphylococcus epidermidis (S. epidermidis) and Pseudomonas aeruginosa (P. aeruginosa) to evaluate the bacterial-surface behavior by FE-SEM and viability calculation. In addition, the initial effects of human osteoblasts were tested on the materials. Gram-negative bacteria showed promoted adherence and viability over the flat and rough surface, while NTs displayed opposite activity with altered morphology. Gram-positive bacteria illustrated similar cellular architecture over the surfaces but with promoted surface adhesion bonds on the flat alloy. Rough surfaces supported S. epidermidis viability, whilst NTs exhibited lower vitality. NTs advocated promoted better osteoblast organization with enhanced vitality. Gram-positive bacteria suggested preferred adhesion capability over flat and carbon-rich surfaces. Gram-negative bacteria were strongly disturbed by NTs but largely stimulated by flat and rough materials. Our work proposed that the chemical profile of the material surface and the bacterial cell wall characteristics might play an important role in the bacteria-surface interactions. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Electrophilic Trifluoromethylselenolation of Boronic Acids
Molecules 2017, 22(5), 833; doi:10.3390/molecules22050833
Received: 1 May 2017 / Revised: 13 May 2017 / Accepted: 15 May 2017 / Published: 19 May 2017
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Abstract
Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF3SeCl and use it in various reactions. Herein, we continue our
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Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF3SeCl and use it in various reactions. Herein, we continue our study of the reactivity scope of this preformed reagent. Cross-coupling reactions with aromatic and heteroaromatic boronic acids have been investigated. The expected products have been obtained, using a stoichiometric amount of copper, with moderate yields. Full article
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Open AccessArticle In Vitro Glucuronidation and Sulfation of ε-Viniferin, a Resveratrol Dimer, in Humans and Rats
Molecules 2017, 22(5), 733; doi:10.3390/molecules22050733
Received: 14 March 2017 / Revised: 21 April 2017 / Accepted: 27 April 2017 / Published: 3 May 2017
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Abstract
ε-Viniferin is a resveratrol dimer that possesses antioxidant or anti-inflammatory activities. However little is known about the metabolism of this oligostilbene. This study was thus undertaken as a first approach to identify and characterize the metabolites of ε-viniferin and to describe the kinetic
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ε-Viniferin is a resveratrol dimer that possesses antioxidant or anti-inflammatory activities. However little is known about the metabolism of this oligostilbene. This study was thus undertaken as a first approach to identify and characterize the metabolites of ε-viniferin and to describe the kinetic profile of their appearance in humans and rats. The glucuronides and sulfates of ε-viniferin were first obtained by chemical hemi-synthesis and were fully characterized by UPLC-MS and NMR spectroscopy. Then, ε-viniferin was incubated with human or rat S9 liver fractions that led to the formation of four glucuronoconjugates and four sulfoconjugates. In both species, ε-viniferin was subjected to an intense metabolism as 70 to 80% of the molecule was converted to glucuronides and sulfates. In humans, the hepatic clearance of ε-viniferin (Vmax/Km) for glucuronidation and sulfation were 4.98 and 6.35 µL/min/mg protein, respectively, whereas, in rats, the hepatic clearance for glucuronidation was 20.08 vs. 2.59 µL/min/mg protein for sulfation. In humans, three major metabolites were observed: two glucuronides and one sulfate. By contrast, only one major glucuronide was observed in rats. This strong hepatic clearance of ε-viniferin in human and rat could explain its poor bioavailability and could help to characterize its active metabolites. Full article
(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)
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Open AccessArticle Dynamic Changes in Neutral and Acidic Ginsenosides with Different Cultivation Ages and Harvest Seasons: Identification of Chemical Characteristics for Panax ginseng Quality Control
Molecules 2017, 22(5), 734; doi:10.3390/molecules22050734
Received: 13 March 2017 / Revised: 24 April 2017 / Accepted: 27 April 2017 / Published: 4 May 2017
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Abstract
In this study, dynamic changes in ginsenoside content and ratios in the Panax ginseng root were investigated with different cultivation ages and different collection months, using high-performance liquid chromatography (HPLC). Our data indicate that changes in ginsenoside Ro and malonyl ginsenosides content were
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In this study, dynamic changes in ginsenoside content and ratios in the Panax ginseng root were investigated with different cultivation ages and different collection months, using high-performance liquid chromatography (HPLC). Our data indicate that changes in ginsenoside Ro and malonyl ginsenosides content were dependent on the ginseng cultivation age (p < 0.05); especially, the Ro content varied from 0.16 to 4.91 mg/g, with a difference about 30-fold. Further, we found that the samples of 5 and 6-year-old P. ginseng had high Ro/Re ratio, whereas two and three-year-old P. ginseng possessed low Ro/Re ratio. Thus, the Ro/Re ratio can be used as a characteristic marker for differentiating the age of the root. The relative content of ginsenosides Rg1 and Re were affected by the ginseng’s harvest season. The Re content was higher than the Rg1 content in May and June, but lower than the Rg1 content from August to October. Thus, the Rg1/Re ratio can be used as a characteristic marker for differentiating the ginseng’s harvest seasons. These results indicate that the chemical characteristics of P. ginseng at different cultivation ages and harvest seasons are clearly different, which may cause differences in pharmacological activities and therapeutic effects. In addition, we developed HPLC coupled with hierarchical cluster analysis and principal component analysis methods to identify the cultivation age and harvest season of P. ginseng using characteristic ginsenosides. Our results showed that this method can be used to discriminate the cultivation age and harvest season of P. ginseng. Full article
(This article belongs to the Special Issue Current Trends in Ginseng Research)
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Open AccessArticle Characterization of Chinese Unifloral Honeys Based on Proline and Phenolic Content as Markers of Botanical Origin, Using Multivariate Analysis
Molecules 2017, 22(5), 735; doi:10.3390/molecules22050735
Received: 5 April 2017 / Revised: 27 April 2017 / Accepted: 28 April 2017 / Published: 17 May 2017
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Abstract
The phenolic and proline content were determined in honey samples of different floral origins (rapeseed, sunflower, buckwheat and Codonopsis) from five different regions of China. The phenolic and proline profile of these samples were used to construct a statistical model to distinguish
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The phenolic and proline content were determined in honey samples of different floral origins (rapeseed, sunflower, buckwheat and Codonopsis) from five different regions of China. The phenolic and proline profile of these samples were used to construct a statistical model to distinguish honeys from different floral origins. Significant differences were identified among the studied honey samples from multivariate chemometric methods. The proline content varied among the four types of honeys, with the values decreasing in the order: buckwheat > Codonopsis > sunflower > rapeseed. Rapeseed honeys contained a high level of benzoic acid, while rutin, p-coumaric acid, p-hydroxybenzoic acid were present at relatively high levels in buckwheat honeys. Principal component analysis (PCA) revealed that rapeseed honey could be distinguished from the other three unifloral honeys, and benzoic acid, proline and kaempferol could serve as potential floral markers. Using 18 phenolic compounds and proline the honey samples were satisfactorily classified according to floral origin at 94% correct prediction by linear discriminant analysis (LDA). The results indicated that phenolic compounds and proline were useful for the identification of the floral origin of the four type honeys. Full article
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Open AccessArticle Emulsion-Based Intradermal Delivery of Melittin in Rats
Molecules 2017, 22(5), 836; doi:10.3390/molecules22050836
Received: 14 March 2017 / Revised: 16 May 2017 / Accepted: 16 May 2017 / Published: 19 May 2017
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Abstract
Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed
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Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed rat skin. A formulated emulsion containing 1% (w/v) BV was prepared. The emulsion was compared with distilled water (DW) and 25% (w/v) N-methyl-2-pyrrolidone (NMP) in DW. Permeation of melittin from aqueous solution through the dermatomed murine skin was evaluated using the Franz diffusion cells. Samples of receptor cells withdrawn at pre-determined time intervals were measured for melittin amount. After the permeation study, the same skin was used for melittin extraction. In addition, a known amount of melittin (5 μg/mL) was added to stratum corneum, epidermis, and dermis of the rat skin, and the amount of melittin was measured at pre-determined time points. The measurement of melittin from all samples was done with HPLC-MS/MS. No melittin was detected in the receptor phase at all time points in emulsion, DW, or NMP groups. When the amount of melittin was further analyzed in stratum corneum, epidermis, and dermis from the permeation study, melittin was still not detected. In an additional experiment, the amount of melittin added to all skin matrices was corrected against the amount of melittin recovered. While the total amount of melittin was retained in the stratum corneum, less than 10% of melittin remained in epidermis and dermis within 15 and 30 min, respectively. Skin microporation with BV emulsion facilitates the penetration of melittin across the stratum corneum into epidermis and dermis, where emulsified melittin could have been metabolized by locally-occurring enzymes. Full article
(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)
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Open AccessArticle Ontogenetic Variation of Individual and Total Capsaicinoids in Malagueta Peppers (Capsicum frutescens) during Fruit Maturation
Molecules 2017, 22(5), 736; doi:10.3390/molecules22050736
Received: 30 March 2017 / Revised: 28 April 2017 / Accepted: 30 April 2017 / Published: 3 May 2017
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Abstract
The ontogenetic variation of total and individual capsaicinoids (nordihydrocapsaicin (n-DHC), capsaicin (C), dihydrocapsaicin (DHC), homocapsaicin (h-C) and homodihydrocapsaicin (h-DHC)) present in Malagueta pepper (Capsicum frutescens) during fruit ripening has been studied. Malagueta peppers were grown in a greenhouse under controlled temperature
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The ontogenetic variation of total and individual capsaicinoids (nordihydrocapsaicin (n-DHC), capsaicin (C), dihydrocapsaicin (DHC), homocapsaicin (h-C) and homodihydrocapsaicin (h-DHC)) present in Malagueta pepper (Capsicum frutescens) during fruit ripening has been studied. Malagueta peppers were grown in a greenhouse under controlled temperature and humidity conditions. Capsaicinoids were extracted using ultrasound-assisted extraction (UAE) and the extracts were analyzed by ultra-performance liquid chromatography (UHPLC) with fluorescence detection. A significant increase in the total content of capsaicinoids was observed in the early days (between 12 and 33). Between day 33 and 40 there was a slight reduction in the total capsaicinoid content (3.3% decrease). C was the major capsaicinoid, followed by DHC, n-DHC, h-C and h-DHC. By considering the evolution of standardized values of the capsaicinoids it was verified that n-DHC, DHC and h-DHC (dihydrocapsaicin-like capsaicinoids) present a similar behavior pattern, while h-C and C (capsaicin-like capsaicinoids) show different evolution patterns. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis, Crystal Structures and Properties of Ferrocenyl Bis-Amide Derivatives Yielded via the Ugi Four-Component Reaction
Molecules 2017, 22(5), 737; doi:10.3390/molecules22050737
Received: 29 March 2017 / Revised: 21 April 2017 / Accepted: 27 April 2017 / Published: 4 May 2017
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Abstract
Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular
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Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular morphologies and create a 14-membered ring motif in the centro-symmetric dimers generated in the solid state. Moreover, the electrochemical behavior of these ferrocenyl bis-amides was assessed by cyclic voltammetry. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Design, Synthesis and Fungicidal Activity of 2-Substituted Phenyl-2-oxo-, 2-Hydroxy- and 2-Acyloxyethylsulfonamides
Molecules 2017, 22(5), 738; doi:10.3390/molecules22050738
Received: 10 April 2017 / Revised: 29 April 2017 / Accepted: 30 April 2017 / Published: 4 May 2017
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Abstract
Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl
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Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl derivatives. A series of thirty-eight 2-substituted phenyl-2-oxo- III, 2-hydroxy- IV and 2-acyloxyethylsulfonamides V were obtained and their structures confirmed by IR, 1H-NMR, and elemental analysis. The in vitro and in vivo bioactivities against two Botrytis cinerea strains, DL-11 and HLD-15, which differ in their sensitivity to procymidone, were evaluated. The in vitro activity results showed that the EC50 values of compounds V-1 and V-9 were 0.10, 0.01 mg L−1 against the sensitive strain DL-11 and 3.32, 7.72 mg L−1 against the resistant strain HLD-15, respectively. For in vivo activity against B. cinerea, compound V-13 and V-14 showed better control effect than the commercial fungicides procymidone and pyrimethanil. The further in vitro bioassay showed that compounds III, IV and V had broad fungicidal spectra against different phytopathogenic fungi. Most of the title compounds showed high fungicidal activities, which could be used as lead compounds for further developing novel fungicidal compounds against Botrytis cinerea. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle The Combined Use of Schizosaccharomyces pombe and Lachancea thermotolerans—Effect on the Anthocyanin Wine Composition
Molecules 2017, 22(5), 739; doi:10.3390/molecules22050739
Received: 22 February 2017 / Revised: 21 April 2017 / Accepted: 25 April 2017 / Published: 4 May 2017
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Abstract
The most popular methodology to make red wine is through the combined use of Saccharomyces cerevisiae yeast and lactic acid bacteria, for alcoholic fermentation and malolactic fermentation respectively. This classic winemaking practice produces stable red wines from a microbiological point of view. This
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The most popular methodology to make red wine is through the combined use of Saccharomyces cerevisiae yeast and lactic acid bacteria, for alcoholic fermentation and malolactic fermentation respectively. This classic winemaking practice produces stable red wines from a microbiological point of view. This study aims to investigate a recent red winemaking biotechnology, which through the combined use of Lachancea thermotolerans and Schizosaccharomyces pombe is used as an alternative to the classic malolactic fermentation. In this new methodology, Schizosaccharomyces pombe totally consumes malic acid, while Lachancea thermotolerans produces lactic acid, avoiding excessive deacidification of musts with low acidity in warm viticulture areas such as Spain. This new methodology has been reported to be a positive alternative to malolactic fermentation in low acidity wines, since it has the advantage to produce wines with a more fruity flavor, less acetic acid, less ethyl carbamate originators and less biogenic amines than the traditional wines produced via conventional fermentation techniques. The study focuses on unexplored facts related to this novel biotechnology such as color and anthocyanin profile. Full article
(This article belongs to the collection Wine Chemistry)
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Open AccessArticle Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life
Molecules 2017, 22(5), 839; doi:10.3390/molecules22050839
Received: 31 March 2017 / Revised: 5 May 2017 / Accepted: 15 May 2017 / Published: 19 May 2017
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Abstract
The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation
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The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration–effect (E/c) curves for the determination), the consequent accumulation of endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditional receptor theory-independent approach). In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidly eliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N1-propylxanthine), an irreversible A1 adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI. Full article
(This article belongs to the Special Issue Adenosine Receptors)
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Open AccessArticle Exploring the Pivotal Role of the CK2 Hinge Region Sub-Pocket in Binding with Tricyclic Quinolone Analogues by Computational Analysis
Molecules 2017, 22(5), 840; doi:10.3390/molecules22050840
Received: 14 April 2017 / Revised: 12 May 2017 / Accepted: 17 May 2017 / Published: 19 May 2017
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Abstract
Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clinical trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC50 > 500 nM)
[...] Read more.
Protein kinase CK2 has been considered as an attractive therapeutic target of cancer therapy. The tricyclic quinoline compound CX-4945 is the first representative of CK2 inhibitors used in human clinical trials. The binding of non-2,6-naphtyridine substituted compounds 27e (IC50 > 500 nM) and 27h (IC50 > 1000 nM) to CK2 is abolished. However, the unbinding mechanisms due to the key pharmacophore group replacement of compounds 27e and 27h are unveiled. In the present work, combined computational analysis was performed to investigate the underlying structural basis of the low-affinity of two systems. As indicated in the results, the loss of hydrogen bonds between the non-2,6-naphtyridine and the hinge region destroyed the proper recognition of the two complexes. Besides, the allosteric mechanisms between the deviated ligands and the changed regions (G-loop, C-loop and β4/β5 loop) are proposed. Furthermore, energetic analysis was evaluated by detailed energy calculation and residue-based energy decomposition. More importantly, the summary of known polar pharmacophore groups elucidates the pivotal roles of hinge region sub-pocket in the binding of CK2 inhibitors. These results provide rational clues to the fragment-based design of more potent CK2 inhibitors. Full article
(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)
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Open AccessArticle Off-Center Rotation of CuPc Molecular Rotor on a Bi(111) Surface and the Chiral Feature
Molecules 2017, 22(5), 740; doi:10.3390/molecules22050740
Received: 10 April 2017 / Revised: 30 April 2017 / Accepted: 2 May 2017 / Published: 4 May 2017
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Abstract
Molecular rotors with an off-center axis and the chiral feature of achiral CuPc molecules on a semi-metallic Bi(111) surface have been investigated by means of a scanning tunneling microscopy (STM) at liquid nitrogen (LN2) temperature. The rotation axis of each CuPc
[...] Read more.
Molecular rotors with an off-center axis and the chiral feature of achiral CuPc molecules on a semi-metallic Bi(111) surface have been investigated by means of a scanning tunneling microscopy (STM) at liquid nitrogen (LN2) temperature. The rotation axis of each CuPc molecular rotor is located at the end of a phthalocyanine group. As molecular coverage increases, the CuPc molecules are self-assembled into various nanoclusters and finally into two-dimensional (2D) domains, in which each CuPc molecule exhibits an apparent chiral feature. Such chiral features of the CuPc molecules can be attributed to the combined effect of asymmetric charge transfer between the CuPc and Bi(111) substrate, and the intermolecular van der Waals interactions. Full article
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Open AccessArticle Synthesis of 1,2,3-Triazolo[4,5-h]quinolone Derivatives with Novel Anti-Microbial Properties against Metronidazole Resistant Helicobacter pylori
Molecules 2017, 22(5), 841; doi:10.3390/molecules22050841
Received: 13 April 2017 / Revised: 8 May 2017 / Accepted: 15 May 2017 / Published: 20 May 2017
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Abstract
Helicobacter pylori infection can lead to gastritis, peptic ulcer, and the development of mucosa associated lymphoid tissue (MALT) lymphoma. Treatment and eradication of H. pylori infection can prevent relapse and accelerate the healing of gastric and duodenal ulcers as well as regression of
[...] Read more.
Helicobacter pylori infection can lead to gastritis, peptic ulcer, and the development of mucosa associated lymphoid tissue (MALT) lymphoma. Treatment and eradication of H. pylori infection can prevent relapse and accelerate the healing of gastric and duodenal ulcers as well as regression of malignancy. Due to the increasing emergence of antibiotic resistance among clinical isolates of H. pylori, alternative approaches using newly discovered antimicrobial agents in combination with the standard antibiotic regimens for the treatment of H. pylori are of major importance. The purpose of the present study was to investigate the effect of newly synthesized 8-amino 7-substituted fluoroquinolone and their correspondent cyclized triazolo derivatives when either alone or combined with metronidazole against metronidazole-resistant H. pylori. Based on standard antimicrobial susceptibility testing methods and checkerboard titration assay, all of the tested compounds showed interesting antimicrobial activity against 12 clinical strains of H. pylori, with best in vitro effect for compounds 4b and 4c. Fractional inhibitory concentration (FIC) mean values showed synergistic pattern in all compounds of Group 5. In addition, additive activities of some of the tested compounds of Group 4 were observed when combined with metronidazole. In contrast, the tested compounds showed no significant urease inhibition activity. These results support the potential of new fluoroquinolone derivatives to be useful in combination with anti-H. pylori drugs in the management of H. pylori-associated diseases. Full article
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Open AccessArticle A Cost-Efficient Method for Unsymmetrical Meso-Aryl Porphyrin Synthesis Using NaY Zeolite as an Inorganic Acid Catalyst
Molecules 2017, 22(5), 741; doi:10.3390/molecules22050741
Received: 7 April 2017 / Revised: 28 April 2017 / Accepted: 2 May 2017 / Published: 5 May 2017
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Abstract
Herein we report the synthesis of unsymmetrical meso-aryl substituted porphyrins, using NaY zeolite as an inorganic acid catalyst. A comparative study between this method and the several synthetic strategies available in the literature was carried out. Our method presented a better, more
[...] Read more.
Herein we report the synthesis of unsymmetrical meso-aryl substituted porphyrins, using NaY zeolite as an inorganic acid catalyst. A comparative study between this method and the several synthetic strategies available in the literature was carried out. Our method presented a better, more cost-efficient rationale and displayed a significantly lower environmental impact. Furthermore, it was possible to verify the scalability of the process as well as the reutilization of the inorganic catalyst NaY (up to 6 times) without significant yield decrease. In addition, this method was applied to the synthesis of several other unsymmetrical porphyrins, from a low melting point porphyrin to mono-carboxylated halogenated unsymmetrical porphyrins, in yields higher than those found in the literature. Additionally, for the first time, two acetamide functionalized halogenated porphyrins were prepared in high yields. This methodology opens the way to the preparation of high yielding functionalized porphyrins, which can be easily immobilized for a variety of applications, either in catalysis or in biomedicine. Full article
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Open AccessArticle Three New Abietane-Type Diterpenoids from Callicarpa macrophylla Vahl.
Molecules 2017, 22(5), 842; doi:10.3390/molecules22050842
Received: 20 March 2017 / Revised: 12 May 2017 / Accepted: 13 May 2017 / Published: 19 May 2017
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Abstract
Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and
[...] Read more.
Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). All the isolated three compounds were evaluated for inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells by using MTT assays. Compounds 1, 2 and 3 showed potent inhibitory activity, with inhibition rates of 34.47–40.13%. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle AlCl3·6H2O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone Methide Moiety of Celastrol
Molecules 2017, 22(5), 742; doi:10.3390/molecules22050742
Received: 8 March 2017 / Revised: 26 April 2017 / Accepted: 27 April 2017 / Published: 16 May 2017
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Abstract
A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl3·6H2O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %,
[...] Read more.
A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl3·6H2O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at ambient temperature and reaction time is only 3 h. The product yields range from 20% to 99%. A reaction mechanism is also proposed, based on our experiment results. Full article
(This article belongs to the Special Issue Synthesis and Modification of Natural Product)
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Open AccessCommunication Rapidly Simultaneous Determination of Six Effective Components in Cistanche tubulosa by Near Infrared Spectroscopy
Molecules 2017, 22(5), 843; doi:10.3390/molecules22050843
Received: 11 April 2017 / Revised: 6 May 2017 / Accepted: 16 May 2017 / Published: 19 May 2017
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Abstract
Quantitative determination of multiple effective components in a given plant usually requires a very large amount of authentic natural products. In this study, we proposed a rapid and non-destructive method for the simultaneous determination of echinacoside, verbascoside, mannitol, sucrose, glucose and fructose in
[...] Read more.
Quantitative determination of multiple effective components in a given plant usually requires a very large amount of authentic natural products. In this study, we proposed a rapid and non-destructive method for the simultaneous determination of echinacoside, verbascoside, mannitol, sucrose, glucose and fructose in Cistanche tubulosa by near infrared spectroscopy (NIRS). Near infrared diffuse reflectance spectroscopy (DRS) and high performance liquid chromatography (HPLC) were conducted on 116 batches of C. tubulosa samples. The DRS data were processed using standard normal variety (SNV) and multiplicative scatter correction (MSC) methods. Partial least squares regression (PLSR) was utilized to build calibration models for components-of-interest in C. tubulosa. All models were then assessed by calculating the root mean square error of calibration (RMSEC), correlation coefficient of calibration (r). The r values of all six calibration models were determined to be greater than 0.94, suggesting each model is reliable. Therefore, the quantitative NIR models reported in this study can be qualified to accurately quantify the contents of six medicinal components in C. tubulosa. Full article
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Open AccessArticle Enhanced Production of Gypenoside LXXV Using a Novel Ginsenoside-Transforming β-Glucosidase from Ginseng-Cultivating Soil Bacteria and Its Anti-Cancer Property
Molecules 2017, 22(5), 844; doi:10.3390/molecules22050844
Received: 14 March 2017 / Revised: 7 May 2017 / Accepted: 12 May 2017 / Published: 19 May 2017
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Abstract
Minor ginsenosides, such as compound K, Rg3(S), which can be produced by deglycosylation of ginsenosides Rb1, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb
[...] Read more.
Minor ginsenosides, such as compound K, Rg3(S), which can be produced by deglycosylation of ginsenosides Rb1, showed strong anti-cancer effects. However, the anticancer effects of gypenoside LXXV, which is one of the deglycosylated shapes of ginsenoside Rb1, is still unknown due to the rarity of its content in plants. Here, we cloned and characterized a novel ginsenoside-transforming β-glucosidase (BglG167b) derived from Microbacterium sp. Gsoil 167 which can efficiently hydrolyze gypenoside XVII into gypenoside LXXV, and applied it to the production of gypenoside LXXV at the gram-scale with high specificity. In addition, the anti-cancer activity of gypenoside LXXV was investigated against three cancer cell lines (HeLa, B16, and MDA-MB231) in vitro. Gypenoside LXXV significantly reduced cell viability, displaying an enhanced anti-cancer effect compared to gypenoside XVII and Rb1. Taken together, this enzymatic method would be useful in the preparation of gypenoside LXXV for the functional food and pharmaceutical industries. Full article
(This article belongs to the Special Issue Synthesis and Modification of Natural Product)
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Open AccessArticle Quercetin from Polygonum capitatum Protects against Gastric Inflammation and Apoptosis Associated with Helicobacter pylori Infection by Affecting the Levels of p38MAPK, BCL-2 and BAX
Molecules 2017, 22(5), 744; doi:10.3390/molecules22050744
Received: 30 March 2017 / Revised: 28 April 2017 / Accepted: 28 April 2017 / Published: 6 May 2017
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Abstract
Helicobacter pylori-associated gastritis is a major threat to public health and Polygonum capitatum (PC) may have beneficial effects on the disease. However, the molecular mechanism remains unknown. Quercetin was isolated from PC and found to be a main bioactive compound. The effects
[...] Read more.
Helicobacter pylori-associated gastritis is a major threat to public health and Polygonum capitatum (PC) may have beneficial effects on the disease. However, the molecular mechanism remains unknown. Quercetin was isolated from PC and found to be a main bioactive compound. The effects of quercetin on human gastric cancer cells GES-1 were determined by xCELLigence. H. pylori-infected mouse models were established. All mice were divided into three groups: control (CG, healthy mice), model (MG, H. pylori infection) and quercetin (QG, mouse model treated by quercetin) groups. IL-8 (interleukin-8) levels were detected via enzyme-linked immunosorbent assay (ELISA). Cell cycle and apoptosis were measured by flow cytometry (FCM). Quantitative reverse transcription PCR (qRT-PCR) and Western Blot were used to detect the levels of p38MAPK (38-kD tyrosine phosphorylated protein kinase), apoptosis regulator BCL-2-associated protein X (BAX) and B cell lymphoma gene 2 (BCL-2). The levels of IL-8 were increased by 8.1-fold in a MG group and 4.3-fold in a QG group when compared with a CG group. In a MG group, G0–G1(phases of the cell cycle)% ratio was higher than a CG group while S phase fraction was lower in a model group than in a control group (p < 0.01). After quercetin treatment, G0–G1% ratio was lower in a QG group than a MG group while S phase fraction was higher than a MG group (p < 0.01). Quercetin treatment reduced the levels of p38MAPK and BAX, and increased the levels of BCL-2 when compared with a MG group (p < 0.05). Quercetin regulates the balance of gastric cell proliferation and apoptosis to protect against gastritis. Quercetin protects against gastric inflammation and apoptosis associated with H. pylori infection by affecting the levels of p38MAPK, BCL-2 and BAX. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Preparation and In Vitro Photodynamic Activity of Glucosylated Zinc(II) Phthalocyanines as Underlying Targeting Photosensitizers
Molecules 2017, 22(5), 845; doi:10.3390/molecules22050845
Received: 17 April 2017 / Revised: 9 May 2017 / Accepted: 15 May 2017 / Published: 19 May 2017
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Abstract
Two novel glucosylated zinc(ІІ) phthalocyanines 7a–7b, as well as the acetyl-protected counterparts 6a–6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical,
[...] Read more.
Two novel glucosylated zinc(ІІ) phthalocyanines 7a–7b, as well as the acetyl-protected counterparts 6a–6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a–7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake. Upon illumination, both photosensitizers show high cytotoxicity with IC50 as low as 0.032 µM toward MCF-7 cells, which are attributed to their high cellular uptake and low aggregation tendency in the biological media, promoting the generation of intracellular reactive oxygen species (ROS). Confocal laser fluorescence microscopic studies have also revealed that they have high and selective affinities to the lysosomes, but not the mitochondria, of MCF-7 cells. The results show that these two glucosylated zinc(II) phthalocyanines are potential anticancer agents for targeting photodynamic therapy. Full article
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Open AccessArticle Modulation of HO-1 by Ferulic Acid Attenuates Adipocyte Differentiation in 3T3-L1 Cells
Molecules 2017, 22(5), 745; doi:10.3390/molecules22050745
Received: 11 March 2017 / Revised: 28 April 2017 / Accepted: 3 May 2017 / Published: 5 May 2017
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Abstract
Ferulic acid (FA) is phenolic compound found in fruits. Many studies have reported that FA has diverse therapeutic effects against metabolic diseases. However, the mechanism by which FA modulates adipogenesis via the expression of heme oxygenase-1 (HO-1) implicated in suppression of adipocyte differentiation
[...] Read more.
Ferulic acid (FA) is phenolic compound found in fruits. Many studies have reported that FA has diverse therapeutic effects against metabolic diseases. However, the mechanism by which FA modulates adipogenesis via the expression of heme oxygenase-1 (HO-1) implicated in suppression of adipocyte differentiation is not fully understood. We investigated whether HO-1 can be activated by FA and suppress adipogenic factors in 3T3-L1. Our results showed that FA suppresses triglyceride-synthesizing enzymes, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). We observed that the expression of CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) were suppressed by FA. In addition, HO-1 inhibitor stimulated lipid accumulation, while FA attenuated lipid accumulation in 3T3-L1 treated with HO-1 inhibitor. We also observed that the expression of HO-1 had the same tendency as C/EBP homologous protein 10 (CHOP10) during the mitotic clonal expansion (MCE) of adipogenesis. We next employed siRNA against HO-1 to clarify whether HO-1 regulates CHOP10. The results indicated that CHOP10 is downstream of HO-1. Furthermore, FA-mediated HO-1/CHOP10 axis activation prevented the initiation of MCE. Therefore, we demonstrated that FA is a positive regulator of HO-1 in 3T3-L1, and may be an effective bioactive compound to reduce adipocyte tissue mass. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Roles of Glycoproteins in the Diagnosis and Differential Diagnosis of Chronic and Latent Keshan Disease
Molecules 2017, 22(5), 746; doi:10.3390/molecules22050746
Received: 27 March 2017 / Revised: 29 April 2017 / Accepted: 2 May 2017 / Published: 8 May 2017
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Abstract
We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50
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We aimed to explore the roles of glycoproteins in the pathogenesis of chronic and latent Keshan disease (CKD and LKD), and screen the lectins as indicators of significant differences in glycoproteins of KD saliva and serum. Blood and saliva were collected from 50 CKD, 50 LKD patients and 54 normal individuals. Saliva and serum lectin microarrays and saliva and serum microarrays were used to screen and verify the differences in the levels of lectin among the three groups. In the male saliva lectin microarray, Solanum tuberosum (potato) lectin (STL) and other 9 lectins showed differences between CKD and normal; STL and other 9 lectins showed differences between LKD and normal; Aleuria aurantia lectin (AAL) and other 15 lectins showed differences between CKD and LKD. In the female saliva microarray, Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I) and other 9 lectins showed differences between CKD and normal; STL and other 7 lectins showed differences between LKD and normal; Maackia amurensis lectin I (MAL-I) and Triticum vulgaris (WGA) showed difference between CKD and LKD. In the male serum lectin microarray, Psophocarpus tetragonolobus lectin I (PTL-I) and other 16 lectins showed differences between CKD and normal; Ulexeuropaeus agglutinin I (UEA-I) and other 9 lectins showed differences between LKD and normal; AAL and other 13 lectins showed differences between CKD and LKD. In the female serum lectin microarray, WGA and other 13 lectins showed differences between CKD and normal; Euonymus europaeus lectin (EEL) and other 6 lectins showed differences between LKD and normal; MAL-I and other 14 lectins showed differences between CKD and LKD. Carbohydrate chain GlcNAc and α-Gal may play crucial roles in the pathogenesis of KD. STL may be considered the diagnostic biomarker for male CKD and LKD, while WGA may be useful in distinguishing between the two stages. STL may be considered the diagnostic biomarker for female LKD. Full article
(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)
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Open AccessArticle Study on the Alkylation Reactions of N(7)-Unsubstituted 1,3-Diazaoxindoles
Molecules 2017, 22(5), 846; doi:10.3390/molecules22050846
Received: 9 April 2017 / Revised: 13 May 2017 / Accepted: 16 May 2017 / Published: 19 May 2017
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Abstract
The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were
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The chemistry of the 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1,3-diazaoxindole) compound family, possessing a drug-like scaffold, is unexplored. In this study, the alkylation reactions of N(7)-unsubstituted 5-isopropyl-1,3-diazaoxindoles bearing various substituents at the C(2) position have been investigated. The starting compounds were synthesized from the C(5)-unsubstituted parent compounds by condensation with acetone and subsequent catalytic reduction of the 5-isopropylidene moiety. Alkylation of the thus obtained 5-isopropyl derivatives with methyl iodide or benzyl bromide in the presence of a large excess of sodium hydroxide led to 5,7-disubstituted derivatives. Use of butyllithium as the base rendered alkylation in the C(5) position possible with reasonable selectivity, without affecting the N(7) atom. During the study on the alkylation reactions, some interesting by-products were also isolated and characterized. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Functional Mitochondria Are Important for the Effect of Resveratrol
Molecules 2017, 22(5), 847; doi:10.3390/molecules22050847
Received: 13 March 2017 / Revised: 15 May 2017 / Accepted: 16 May 2017 / Published: 20 May 2017
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Abstract
Resveratrol (Resv) is a polyphenol reported to modulate mitochondrial activity. The aim was to use HeLa and 143B cells to characterize the action of Resv on mitochondrial activity, cell size and proliferation using wild type (WT) and Rho 0 cells deficient in mitochondrial
[...] Read more.
Resveratrol (Resv) is a polyphenol reported to modulate mitochondrial activity. The aim was to use HeLa and 143B cells to characterize the action of Resv on mitochondrial activity, cell size and proliferation using wild type (WT) and Rho 0 cells deficient in mitochondrial DNA. In both HeLa WT and Rho 0 cells, the oxygen consumption rate (OCR) was increased at 20 µM Resv after 24 h, whereas only a non-significant increase of OCR was observed in 143B WT cells. Resv decreased cell number concentration-dependently in both WT and Rho 0 cell types. An increased cell diameter was observed in HeLa WT, but not in Rho 0 when treated with Resv. Overall, the findings presented indicate that functional mitochondria are a prerequisite for cell enlargement by Resv. Full article
(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)
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Open AccessArticle In Vitro Anticancer Activity and Structural Characterization of Ubiquinones from Antrodia cinnamomea Mycelium
Molecules 2017, 22(5), 747; doi:10.3390/molecules22050747
Received: 23 March 2017 / Revised: 22 April 2017 / Accepted: 3 May 2017 / Published: 6 May 2017
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Abstract
Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae) mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones
[...] Read more.
Two new ubiquinones, named antrocinnamone and 4-acetylantrocamol LT3, were isolated along with six known ubiquinones from Antrodia cinnamomea (Polyporaceae) mycelium. The developed HPLC analysis methods successfully identified eight different ubiquinones, two benzenoids, and one maleic acid derivative from A. cinnamomea. The ubiquinones 18 exhibited potential and selective cytotoxic activity against three human cancer cell lines, with IC50 values ranging from 0.001 to 35.883 μM. We suggest that the different cytotoxicity levels were related to their chemical structures, especially the 4-hydroxycyclohex-2-enone ring and the presence of a free hydroxyl group in the side chain. The suppression by 4-acetylantrocamol LT3 stopped the cell cycle at the beginning of the G2-M phase thus making the cell cycle arrest at the sub-G1 phase as compared with control cells. Full article
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Open AccessArticle Anti-Onchocerca and Anti-Caenorhabditis Activity of a Hydro-Alcoholic Extract from the Fruits of Acacia nilotica and Some Proanthocyanidin Derivatives
Molecules 2017, 22(5), 748; doi:10.3390/molecules22050748
Received: 7 April 2017 / Revised: 2 May 2017 / Accepted: 3 May 2017 / Published: 6 May 2017
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Abstract
Acacia nilotica fruits with high tannin content are used in the northern parts of Cameroon as anti-filarial remedies by traditional healers. In this study, the hydro-alcoholic fruit extract (crude extract (CE)) and, one of the main constituents in its most active fractions, (+)-catechin-3-
[...] Read more.
Acacia nilotica fruits with high tannin content are used in the northern parts of Cameroon as anti-filarial remedies by traditional healers. In this study, the hydro-alcoholic fruit extract (crude extract (CE)) and, one of the main constituents in its most active fractions, (+)-catechin-3-O-gallate (CG), as well as four related proanthocyanidins, (−)-epicatechin-3-O-gallate (ECG), (+)-gallocatechin (GC), (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-O-gallate (EGCG), were assessed for their potential in vitro anthelmintic properties against the free-living model organism Caenorhabditis elegans and against the cattle filarial parasite Onchocerca ochengi. Worms were incubated in the presence of different concentrations of fruit extract, fractions and pure compounds. The effects on mortality were monitored after 48 h. The plant extract and all of the pure tested compounds were active against O. ochengi (LC50 ranging from 1.2 to 11.5 µg/mL on males) and C. elegans (LC50 ranging from 33.8 to 350 µg/mL on wild type). While high LC50 were required for the effects of the compounds on C. elegans, very low LC50 were required against O. ochengi. Importantly, tests for acute oral toxicity (lowest dose: 10 mg/kg) in Wistar rats demonstrated that crude extract and pure compounds were non-toxic and safe to use. Additionally, the results of cytotoxicity tests with the Caco-2 cell line (CC50 ranging from 47.1 to 93.2 µg/mL) confirmed the absence of significant toxicity of the crude extract and pure compounds. These results are in good accordance with the use of A. nilotica against nematode infections by traditional healers, herdsmen and pastoralists in Cameroon. Full article
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Open AccessArticle Photoreactions of Endohedral Metallofullerene with Siliranes: Electronic Properties of Carbosilylated Lu3N@Ih-C80
Molecules 2017, 22(5), 850; doi:10.3390/molecules22050850
Received: 29 April 2017 / Revised: 16 May 2017 / Accepted: 17 May 2017 / Published: 20 May 2017
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Abstract
Photochemical carbosilylation of Lu3N@Ih-C80 was performed using siliranes (silacyclopropanes) to afford the corresponding [5,6]- and [6,6]-adducts. Electrochemical studies indicated that the redox potentials of the carbosilylated derivatives were shifted cathodically in comparison with those of the [5,6]-pyrrolidino
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Photochemical carbosilylation of Lu3N@Ih-C80 was performed using siliranes (silacyclopropanes) to afford the corresponding [5,6]- and [6,6]-adducts. Electrochemical studies indicated that the redox potentials of the carbosilylated derivatives were shifted cathodically in comparison with those of the [5,6]-pyrrolidino adducts. The electronic effect of the silirane addends on Lu3N@Ih-C80 was verified on the basis of density functional theory calculations. Full article
(This article belongs to the Special Issue Cutting-Edge Organic Chemistry in Japan)
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Open AccessArticle A Molecular Electron Density Theory Study of the Reactivity of Azomethine Imine in [3+2] Cycloaddition Reactions
Molecules 2017, 22(5), 750; doi:10.3390/molecules22050750
Received: 10 April 2017 / Revised: 28 April 2017 / Accepted: 30 April 2017 / Published: 6 May 2017
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Abstract
The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using Density Functional Theory (DFT) calculations at the MPWB1K/6-311G(d) level. Topological analysis of the electron localisation
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The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using Density Functional Theory (DFT) calculations at the MPWB1K/6-311G(d) level. Topological analysis of the electron localisation function reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterises this three-atom-component (TAC) as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with moderate activation energy, 8.7 kcal·mol−1. A bonding evolution theory study indicates that this reaction takes place through a non-concerted [2n + 2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the activation energy is only 0.4 kcal·mol−1, in complete agreement with the high polar character of the more favourable regioisomeric transition state structure. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pseudo(mono)radical type (pmr-type) of reactivity. Full article
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Open AccessArticle Constrained Geometry Organotitanium Catalysts Supported on Nanosized Silica for Ethylene (co)Polymerization
Molecules 2017, 22(5), 751; doi:10.3390/molecules22050751
Received: 24 April 2017 / Accepted: 3 May 2017 / Published: 5 May 2017
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Abstract
Supported olefin polymerization catalysts can prevent reactor-fouling problems and produce uniform polymer particles. Constrained geometry complexes (CGCs) have less sterically hindered active sites than bis-cyclopentadienyl metallocene catalysts. In the literature, micrometer-sized silica particles were used for supporting CGC catalysts, which might have strong
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Supported olefin polymerization catalysts can prevent reactor-fouling problems and produce uniform polymer particles. Constrained geometry complexes (CGCs) have less sterically hindered active sites than bis-cyclopentadienyl metallocene catalysts. In the literature, micrometer-sized silica particles were used for supporting CGC catalysts, which might have strong mass transfer limitations. This study aims to improve the activity of supported CGC catalysts by using nanometer-sized silica. Ti[(C5Me4)SiMe2(NtBu)]Cl2, a “constrained-geometry” titanium catalyst, was supported on MAO-treated silicas (nano-sized and micro-sized) by an impregnation method. Ethylene homo-polymerization and co-polymerization with 1-octene were carried out in a temperature range of 80–120 °C using toluene as the solvent. Catalysts prepared and polymers produced were characterized. For both catalysts and for both reactions, the maximum activities occurred at 100 °C, which is significantly higher than that (60 °C) reported before for supported bis-cyclopentadienyl metallocene catalysts containing zirconium, and is lower than that (≥140 °C) used for unsupported Ti[(C5Me4)SiMe2(NtBu)]Me2 catalyst. Activities of nano-sized catalyst were 2.6 and 1.6 times those of micro-sized catalyst for homopolymerization and copolymerization, respectively. The former produced polymers with higher crystallinity and melting point than the latter. In addition, copolymer produced with nanosized catalyst contained more 1-octene than that produced with microsized catalyst. Full article
(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)
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Open AccessArticle Rapid and Cost-Effective Quantification of Glucosinolates and Total Phenolic Content in Rocket Leaves by Visible/Near-Infrared Spectroscopy
Molecules 2017, 22(5), 851; doi:10.3390/molecules22050851
Received: 27 April 2017 / Revised: 17 May 2017 / Accepted: 17 May 2017 / Published: 20 May 2017
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Abstract
The potential of visible-near infrared spectroscopy to predict glucosinolates and total phenolic content in rocket (Eruca vesicaria) leaves has been evaluated. Accessions of the E. vesicaria species were scanned by NIRS as ground leaf, and their reference values regressed against different
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The potential of visible-near infrared spectroscopy to predict glucosinolates and total phenolic content in rocket (Eruca vesicaria) leaves has been evaluated. Accessions of the E. vesicaria species were scanned by NIRS as ground leaf, and their reference values regressed against different spectral transformations by modified partial least squares (MPLS) regression. The coefficients of determination in the external validation (R2VAL) for the different quality components analyzed in rocket ranged from 0.59 to 0.84, which characterize those equations as having from good to excellent quantitative information. These results show that the total glucosinolates, glucosativin and glucoerucin equations obtained, can be used to identify those samples with low and high contents. The glucoraphanin equation obtained can be used for rough predictions of samples and in case of total phenolic content, the equation showed good correlation. The standard deviation (SD) to standard error of prediction ratio (RPD) and SD to range (RER) were variable for the different quality compounds and showed values that were characteristic of equations suitable for screening purposes or to perform accurate analyses. From the study of the MPLS loadings of the first three terms of the different equations, it can be concluded that some major cell components such as protein and cellulose, highly participated in modelling the equations for glucosinolates. Full article
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Open AccessArticle Synthesis and Excellent Duplex Stability of Oligonucleotides Containing 2′-Amino-LNA Functionalized with Galactose Units
Molecules 2017, 22(5), 852; doi:10.3390/molecules22050852
Received: 3 May 2017 / Revised: 17 May 2017 / Accepted: 17 May 2017 / Published: 21 May 2017
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Abstract
A convenient method for the preparation of oligonucleotides containing internally-attached galactose and triantennary galactose units has been developed based on click chemistry between 2′-N-alkyne 2′-amino-LNA nucleosides and azido-functionalized galactosyl building blocks. The synthesized oligonucleotides show excellent binding affinity and selectivity towards
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A convenient method for the preparation of oligonucleotides containing internally-attached galactose and triantennary galactose units has been developed based on click chemistry between 2′-N-alkyne 2′-amino-LNA nucleosides and azido-functionalized galactosyl building blocks. The synthesized oligonucleotides show excellent binding affinity and selectivity towards complementary DNA/RNA strands with an increase in the melting temperature of up to +23.5 °C for triply-modified variants. Full article
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
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Open AccessArticle Synthesis of Europium-Doped Fluorapatite Nanorods and Their Biomedical Applications in Drug Delivery
Molecules 2017, 22(5), 753; doi:10.3390/molecules22050753
Received: 5 April 2017 / Revised: 23 April 2017 / Accepted: 4 May 2017 / Published: 6 May 2017
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Abstract
Europium (Eu)-doped fluorapatite (FA) nanorods have a biocompatibility similar to that of hydroxyapatite (HA) for use as cell imaging biomaterials due to their luminescent property. Here, we discuss the new application of europium-doped fluorapatite (Eu-FA) nanorods as an anticancer drug carrier. The Eu-FA
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Europium (Eu)-doped fluorapatite (FA) nanorods have a biocompatibility similar to that of hydroxyapatite (HA) for use as cell imaging biomaterials due to their luminescent property. Here, we discuss the new application of europium-doped fluorapatite (Eu-FA) nanorods as an anticancer drug carrier. The Eu-FA nanorods were prepared by using a hydrothermal method. The morphology, crystal structure, fluorescence, and composition were investigated. The specific crystal structure enables the effective loading of drug molecules. Doxorubicin (DOX), which was used as a model anticancer drug, effectively loaded onto the surface of the nanorods. The DOX release was pH-dependent and occurred more rapidly at pH 5.5 than at pH 7.4. The intracellular penetration of the DOX-loaded Eu-FA nanorods (Eu-FA/DOX) can be imaged in situ due to the self-fluorescence property. Treatment of melanoma A375 cells with Eu-FA/DOX elicited a more effective apoptosis rate than direct DOX treatment. Overall, Eu-FA exhibits potential for tracking and treating tumors and may be potentially useful as a multifunctional carrier system to effectively load and sustainably deliver drugs. Full article
(This article belongs to the Special Issue Lanthanide Luminescence: Fundamental Research and Applications)
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Open AccessArticle Phytochemical Composition and Antioxidant Capacity of Seven Saskatoon Berry (Amelanchier alnifolia Nutt.) Genotypes Grown in Poland
Molecules 2017, 22(5), 853; doi:10.3390/molecules22050853
Received: 5 April 2017 / Revised: 18 May 2017 / Accepted: 18 May 2017 / Published: 21 May 2017
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Abstract
The basic chemical composition, bioactive compounds, and antioxidant capacity of fruits of three new Polish breeding clones (No. 5/6, type S, and type N) and four Canadian cultivars (cvs.) (“Martin”, “Smoky”, “Pembina”, and “Honeywood”) grown in Poland in 2016 were investigated. Fruits were
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The basic chemical composition, bioactive compounds, and antioxidant capacity of fruits of three new Polish breeding clones (No. 5/6, type S, and type N) and four Canadian cultivars (cvs.) (“Martin”, “Smoky”, “Pembina”, and “Honeywood”) grown in Poland in 2016 were investigated. Fruits were analyzed for their contents of triterpenoids, carotenoids, chlorophylls, and polyphenolics with the ultra-performance liquid chromatography photodiode detector-quadrupole/time-of-flight mass spectrometry (UPLC-PDA-Q/TOF-MS) method, sugar with the high-performance liquid chromatography–evaporative light scattering detector (HPLC-ELSD) method, and antioxidant capacity with the ability to reduce free radical (ABTS) and ferric reducing ability of plasma (FRAP) method. Thirty-eight bioactive compounds, including twenty-eight polyphenolic compounds (four anthocyanins, nine phenolic acids, nine flavonols, and seven flavan-3-ols), four carotenoids, two chlorophylls, and three triterpenoids were identified in the fruits. The fruits of the tested Saskatoon berry genotypes were found to be rich in phenolic compounds (3773.94–6390.36 mg/100 g·dm), triterpenoids (66.55–91.31 mg/kg·dm), and carotenoids (478.62–561.57 mg/kg·dm), with high ABTS and FRAP capacity (10.38–34.49 and 9.66–25.34 mmol·Trolox/100 g·dm, respectively). Additionally, the berries of these genotypes seemed to be a good source of sugar (9.02–19.69 g/100 g), pectins (0.67%–1.33%), and ash (0.59%–0.67%). Some genotypes of Saskatoon berry, especially the clones type S, type N, and cvs. “Honeywood” and “Smoky”, may be selected for their potential applications in commercial cultivation to produce fruits with valuable health-promoting nutritional effects on human health. Additionally, three new genotypes that may offer new functional materials can be recommended for fruit growers. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Protective Effects of Amarogentin against Carbon Tetrachloride-Induced Liver Fibrosis in Mice
Molecules 2017, 22(5), 754; doi:10.3390/molecules22050754
Received: 14 March 2017 / Revised: 30 April 2017 / Accepted: 1 May 2017 / Published: 6 May 2017
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Abstract
Amarogentin, a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots, has been suggested to exhibit many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. The present study was designed to evaluate the protective effects of amarogentin on carbon tetrachloride-induced liver
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Amarogentin, a secoiridoid glycoside that is mainly extracted from Swertia and Gentiana roots, has been suggested to exhibit many biological effects, including anti-oxidative, anti-tumour, and anti-diabetic activities. The present study was designed to evaluate the protective effects of amarogentin on carbon tetrachloride-induced liver fibrosis in vivo and the underlying mechanism. Fibrosis was induced by subcutaneous injections of 6 mL/kg of 20% carbon tetrachloride (dissolved in olive oil) twice per week for seven weeks. Mice were orally treated with 25, 50, and 100 mg/kg amarogentin and with colchicine as a positive control. Biochemical assays and histopathological investigations showed that amarogentin delayed the formation of liver fibrosis; decreased alanine aminotransferase, aspartate aminotransferase, malondialdehyde and hydroxyproline levels; and increased albumin, cyclic guanosine monophosphate, glutathione peroxidase, and superoxide dismutase levels. Moreover, amarogentin exhibited downregulation of α-smooth muscle actin and transforming growth factor-β1 levels in immunohistochemical and Western blot analyses. The levels of phosphorylated extracellular regulated protein kinases, c-Jun N-terminal kinase, and p38 were also significantly reduced in all amarogentin-treated groups in a dose-dependent manner. These findings demonstrated that amarogentin exerted significant hepatoprotective effects against carbon tetrachloride-induced liver fibrosis in mice and suggested that the effect of amarogentin against liver fibrosis may be by anti-oxidative properties and suppressing the mitogen-activated protein kinase signalling pathway. Full article
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