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Molecules, Volume 19, Issue 10 (October 2014), Pages 15361-17065

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Editorial

Jump to: Research, Review, Other

Open AccessEditorial Editorial to the Organophosphorus Chemistry Special Issue of Molecules (2012–2014)
Molecules 2014, 19(10), 15408-15410; doi:10.3390/molecules191015408
Received: 19 September 2014 / Revised: 21 September 2014 / Accepted: 22 September 2014 / Published: 26 September 2014
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Abstract
The review entitled “Organophosphorus Chemistry for the Synthesis of Dendrimers” gives an overview of the methods of synthesis of phosphorus-containing dendrimers, with emphasis on the various roles played by the chemistry of phosphorus [1]. It is demonstrated that the presence of phosphorus atom(s)
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The review entitled “Organophosphorus Chemistry for the Synthesis of Dendrimers” gives an overview of the methods of synthesis of phosphorus-containing dendrimers, with emphasis on the various roles played by the chemistry of phosphorus [1]. It is demonstrated that the presence of phosphorus atom(s) at each branching point of the dendrimeric structure is particularly important and highly valuable. Full article
(This article belongs to the Special Issue Organophosphorus Chemistry)
Open AccessEditorial Special Issue: Intramolecular Hydrogen Bonding
Molecules 2014, 19(10), 15783-15785; doi:10.3390/molecules191015783
Received: 26 September 2014 / Revised: 27 September 2014 / Accepted: 27 September 2014 / Published: 29 September 2014
Cited by 7 | PDF Full-text (610 KB) | HTML Full-text | XML Full-text
Abstract
Intramolecular hydrogen bonds play critical structure- and function-serving roles in biological and synthetic molecular systems. This special issue, through eight contributions, showcases the prominence of these non-covalent interactions within several scientific disciplines, and in various structural contexts and environments. Reported, for example, are
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Intramolecular hydrogen bonds play critical structure- and function-serving roles in biological and synthetic molecular systems. This special issue, through eight contributions, showcases the prominence of these non-covalent interactions within several scientific disciplines, and in various structural contexts and environments. Reported, for example, are the consequences of intramolecular hydrogen bonds on the structures of molecules that show biological activity, for biological mechanisms, and for the conformational switching of functional synthetic molecules. Also showcased in the contributions are the state-of-the-art experimental and theoretical methods available for the characterization of intramolecular hydrogen bonds, which critically report on their strengths, geometries, and spectroscopic signatures in the gas, solid, and solution phases. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)

Research

Jump to: Editorial, Review, Other

Open AccessArticle Biological Evaluation of the Activity of Some Benzimidazole-4,7-dione Derivatives
Molecules 2014, 19(10), 15361-15373; doi:10.3390/molecules191015361
Received: 30 July 2014 / Revised: 9 September 2014 / Accepted: 11 September 2014 / Published: 26 September 2014
Cited by 2 | PDF Full-text (1219 KB) | HTML Full-text | XML Full-text
Abstract
The study presented here is a follow up of the authors’ interest in the approach to selective and cytotoxic bioreductive anticancer prodrugs. The current work is devoted to explore both the biological activity of some previously obtained compounds and the search for an
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The study presented here is a follow up of the authors’ interest in the approach to selective and cytotoxic bioreductive anticancer prodrugs. The current work is devoted to explore both the biological activity of some previously obtained compounds and the search for an explanation of their target(s) in hypoxic pathways. In this work the biological activity of some benzimidazole-4,7-diones was evaluated. These compounds were examined as potential bioreductive agents specific for the hypoxic environment found in tumor cells. The main aim was concerned with establishing their cytotoxic properties by using proliferation, apoptosis and DNA destruction tests on selected tumor cells. Their cytotoxic effects on two tumor cell lines (human lung adenocarcinoma A549 cells line and human malignant melanoma WM115) was compared by means of a WST-1 test. Next, the mode of cytotoxicity behind the selected tumor cells’ death was determined by the caspase 3/7 test. The last point referred to the DNA destruction of A549 and WM115 cells and the in situ DNA Assay Kit test was applied. The cytotoxic tests confirmed their activity against the tumor cells and target hypoxia (compounds 2b, 2a, 2d). The screening test of the caspase-dependent apoptosis proved that the exposure of the tested tumor cells in hypoxia to these benzimidazole-4,7-diones promoted the apoptotic cell death. Additionally, the DNA damage test established that benzimidazole-4,7-diones can be potential hypoxia-selective agents for tumor cells, especially compound 2b. All results classify the tested benzimidazole-4,7-diones as promising, lead molecules and provide a rationale for further molecular studies to explain their usefulness as potential inhibitors of the hypoxia-inducible factor 1 (HIF1). Full article
Open AccessArticle Identification of Three Elicitins and a Galactan-Based Complex Polysaccharide from a Concentrated Culture Filtrate of Phytophthora infestans Efficient against Pectobacterium atrosepticum
Molecules 2014, 19(10), 15374-15390; doi:10.3390/molecules191015374
Received: 29 July 2014 / Revised: 10 September 2014 / Accepted: 15 September 2014 / Published: 26 September 2014
Cited by 3 | PDF Full-text (1047 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The induction of plant immunity by Pathogen Associated Molecular Patterns (PAMPs) constitutes a powerful strategy for crop protection. PAMPs indeed induce general defense responses in plants and thus increase plant resistance to pathogens. Phytophthora infestans culture filtrates (CCFs) are known to induce defense
[...] Read more.
The induction of plant immunity by Pathogen Associated Molecular Patterns (PAMPs) constitutes a powerful strategy for crop protection. PAMPs indeed induce general defense responses in plants and thus increase plant resistance to pathogens. Phytophthora infestans culture filtrates (CCFs) are known to induce defense responses and decrease the severity of soft rot due to Pectobacterium atrosepticum in potato tubers. The aim of this study was to identify and characterize the active compounds from P. infestans filtrate. The filtrate was fractionated by gel filtration, and the protection effects against P. atrosepticum and the ability to induce PAL activity were tested for each fraction. The fraction active in protection (F1) also induced PAL activity, as did the whole filtrate. Three elicitins (INF1, INF4 and INF5) were identified in F1b, subfraction of F1, by MALDI-TOF-MS and MS/MS analyses. However, deproteinized F1b still showed biological activity against the bacterium, revealing the presence of an additional active compound. GC-MS analyses of the deproteinized fraction highlighted the presence of a galactan-based complex polysaccharide. These experiments demonstrate that the biological activity of the CCF against P. atrosepticum results from a combined action of three elicitins and a complex polysaccharide, probably through the activation of general defense responses. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Design and Synthesis of C-Terminal Modified Cyclic Peptides as VEGFR1 Antagonists
Molecules 2014, 19(10), 15391-15407; doi:10.3390/molecules191015391
Received: 7 August 2014 / Revised: 12 September 2014 / Accepted: 17 September 2014 / Published: 26 September 2014
Cited by 4 | PDF Full-text (1728 KB) | HTML Full-text | XML Full-text
Abstract
Previously designed cyclic peptide antagonist c[YYDEGLEE]-NH2 disrupts the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). It represents a promising tool in the fight against cancer and age-related macular degeneration. We described in this paper the optimization of the
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Previously designed cyclic peptide antagonist c[YYDEGLEE]-NH2 disrupts the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). It represents a promising tool in the fight against cancer and age-related macular degeneration. We described in this paper the optimization of the lead peptide by C-terminal modification. A new strategy for the synthesis of cyclic peptides is developed, improving the cyclisation efficiency. At 100 µM, several new peptides with an aromatic group flexibly linked at C-terminal end showed significantly increased receptor binding affinities in competition ELISA test. The most active peptide carrying a coumarin group may be a useful tool in anti-angiogenic biological studies. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Open AccessArticle Design and Synthesis of Thiazolo[5,4-f]quinazolines as DYRK1A Inhibitors, Part II
Molecules 2014, 19(10), 15411-15439; doi:10.3390/molecules191015411
Received: 7 August 2014 / Revised: 15 September 2014 / Accepted: 16 September 2014 / Published: 26 September 2014
Cited by 12 | PDF Full-text (940 KB) | HTML Full-text | XML Full-text
Abstract
The convenient synthesis of a focused library (forty molecules) of novel 6,6,5-tricyclic thiazolo[5,4-f]quinazolines was realized mainly under microwave irradiation. A novel 6-aminobenzo[d]thiazole-2,7-dicarbonitrile (1) was used as a versatile molecular platform for the synthesis of various derivatives. Kinase
[...] Read more.
The convenient synthesis of a focused library (forty molecules) of novel 6,6,5-tricyclic thiazolo[5,4-f]quinazolines was realized mainly under microwave irradiation. A novel 6-aminobenzo[d]thiazole-2,7-dicarbonitrile (1) was used as a versatile molecular platform for the synthesis of various derivatives. Kinase inhibition, of the obtained final compounds, was evaluated on a panel of two kinases (DYRK1A/1B) together with some known reference DYRK1A and DYRK1B inhibitors (harmine, TG003, NCGC-00189310 and leucettine L41). Compound IC50 values were obtained and compared. Five of the novel thiazolo[5,4-f]quinazoline derivatives prepared, EHT 5372 (8c), EHT 6840 (8h), EHT 1610 (8i), EHT 9851 (8k) and EHT 3356 (9b) displayed single-digit nanomolar or subnanomolar IC50 values and are among the most potent DYRK1A/1B inhibitors disclosed to date. DYRK1A/1B kinases are known to be involved in the regulation of various molecular pathways associated with oncology, neurodegenerative diseases (such as Alzheimer disease, AD, or other tauopathies), genetic diseases (such as Down Syndrome, DS), as well as diseases involved in abnormal pre-mRNA splicing. The compounds described in this communication constitute a highly potent set of novel molecular probes to evaluate the biology/pharmacology of DYR1A/1B in such diseases. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessArticle A New Isoflavonoid from Seeds of Lepidium sativum L. and Its Protective Effect on Hepatotoxicity Induced by Paracetamol in Male Rats
Molecules 2014, 19(10), 15440-15451; doi:10.3390/molecules191015440
Received: 2 July 2014 / Revised: 30 July 2014 / Accepted: 26 August 2014 / Published: 26 September 2014
Cited by 3 | PDF Full-text (886 KB) | HTML Full-text | XML Full-text
Abstract
A new isoflavonoid, 5,6-dimethoxy-2',3'-methylenedioxy-7-C-β-d-gluco-pyranosyl isoflavone was isolated from the seeds of Lepidium sativum L. along with two known isoflavonoids, 7-hydroxy-4',5,6-trimethoxyisoflavone and 7-hydroxy-5,6-dimethoxy-2',3'-methylenedioxyisoflavone. The structures of all compounds were elucidated with NMR spectrometry. Compounds 1, 2 and the new isoflavonoid 3 were evaluated
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A new isoflavonoid, 5,6-dimethoxy-2',3'-methylenedioxy-7-C-β-d-gluco-pyranosyl isoflavone was isolated from the seeds of Lepidium sativum L. along with two known isoflavonoids, 7-hydroxy-4',5,6-trimethoxyisoflavone and 7-hydroxy-5,6-dimethoxy-2',3'-methylenedioxyisoflavone. The structures of all compounds were elucidated with NMR spectrometry. Compounds 1, 2 and the new isoflavonoid 3 were evaluated for their ability to reduce the hepatotoxicity induced by paracetamol in male rats by reducing the damage and toxicity effects on liver cells with a significant improvement of total antioxidant capacity, normalizing the levels of liver enzymes GSH, SOD, GPX, CAT and GST compared to control group. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Phytotoxicity of 4,8-Dihydroxy-1-tetralone Isolated from Carya cathayensis Sarg. to Various Plant Species
Molecules 2014, 19(10), 15452-15467; doi:10.3390/molecules191015452
Received: 19 August 2014 / Revised: 15 September 2014 / Accepted: 16 September 2014 / Published: 26 September 2014
Cited by 3 | PDF Full-text (1486 KB) | HTML Full-text | XML Full-text
Abstract
The aqueous extract from Carya cathayensis Sarg. exocarp was centrifuged, filtered, and separated into 11 elution fractions by X-5 macroporous resin chromatography. A phenolic compound, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from the fractions with the strongest phytotoxicity by bioassy-guided fractionation, and investigated for phytotoxicity
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The aqueous extract from Carya cathayensis Sarg. exocarp was centrifuged, filtered, and separated into 11 elution fractions by X-5 macroporous resin chromatography. A phenolic compound, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from the fractions with the strongest phytotoxicity by bioassy-guided fractionation, and investigated for phytotoxicity on lettuce (Latuca sativa L.), radish (Raphanus sativus L.), cucumber (Cucumis sativus L.), onion (Allium cepa L.) and wheat (Triticum aestivum L.). The testing results showed that the treatment with 0.6 mM 4,8-DHT could significantly depress the germination vigor of lettuce and wheat, reduce the germination rate of lettuce and cucumber, and also inhibit radicle length, plumule length, and fresh weight of seedlings of lettuce and onion, but could significantly promote plumule length and fresh weight of seedlings of cucumber (p < 0.05). For the tested five plants, the 4,8-DHT was the most active to the seed germination and seedling growth of lettuce, indicating that the phytotoxicity of 4,8-DHT had the selectivity of dosage, action target (plant type) and content (seed germination or seedling growth). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effect Analysis of Mineral Salt Concentrations on Nosiheptide Production by Streptomyces actuosus Z-10 Using Response Surface Methodology
Molecules 2014, 19(10), 15507-15520; doi:10.3390/molecules191015507
Received: 21 July 2014 / Revised: 2 September 2014 / Accepted: 12 September 2014 / Published: 26 September 2014
Cited by 4 | PDF Full-text (1359 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to develop an optimal combination of mineral salts in the fermentation medium for nosiheptide (Nsh) production using statistical methodologies. A Plackett-Burman design (PBD) was used to evaluate the impacts of eight mineral salts on Nsh production. The
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The objective of this study was to develop an optimal combination of mineral salts in the fermentation medium for nosiheptide (Nsh) production using statistical methodologies. A Plackett-Burman design (PBD) was used to evaluate the impacts of eight mineral salts on Nsh production. The results showed that among the no-significant factors, CaCO3, and K2HPO4·3H2O had positive effects, whereas FeSO4·7H2O, CuSO4·5H2O, and ZnSO4·7H2O had negative effects on Nsh production. The other three significant factors (Na2SO4, MnSO4·H2O, and MgSO4·7H2O) were further optimized by using a five-level three-factor central composite design (CCD). Experimental data were fitted to a quadratic polynomial model, which provided an effective way to determine the interactive effect of metal salts on Nsh production. The optimal values were determined to be 2.63, 0.21, and 3.37 g/L, respectively. The model also ensured a good fitting of scale-up Nsh batch fermentation with a maximum production of 1501 mg/L, representing a 1.56-fold increase compared to the original standard condition. All these results revealed that statistical optimization methodology had the potential to achieve comprehensive optimization in Nsh fermentation behaviors, which indicates a possibility to establish economical large-scale production of Nsh. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Five New Iridoids from Roots of Salvia digitaloides
Molecules 2014, 19(10), 15521-15534; doi:10.3390/molecules191015521
Received: 19 August 2014 / Revised: 30 August 2014 / Accepted: 11 September 2014 / Published: 29 September 2014
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Abstract
Five new iridoids, salvialosides A–E (compounds 15), together with fifty known compounds were isolated from the roots of Salvia digitaloides. The structures of the new compounds were completely elucidated using a combination of 2D NMR techniques (COSY, NOESY, HMQC
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Five new iridoids, salvialosides A–E (compounds 15), together with fifty known compounds were isolated from the roots of Salvia digitaloides. The structures of the new compounds were completely elucidated using a combination of 2D NMR techniques (COSY, NOESY, HMQC and HMBC) and HR-ESI-MS analyses. The known compounds were identified by comparison of their spectroscopic and physical data with those reported in the literature. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Unusual Structure-Energy Correlations in Intramolecular Diels–Alder Reaction Transition States
Molecules 2014, 19(10), 15535-15545; doi:10.3390/molecules191015535
Received: 23 July 2014 / Revised: 1 September 2014 / Accepted: 16 September 2014 / Published: 29 September 2014
Cited by 3 | PDF Full-text (825 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Detailed analysis of calculated data from an experimental/computational study of intramolecular furan Diels–Alder reactions has led to the unusual discovery that the mean contraction of the newly forming C-C σ-bonds from the transition state to the product shows a linear correlation with both
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Detailed analysis of calculated data from an experimental/computational study of intramolecular furan Diels–Alder reactions has led to the unusual discovery that the mean contraction of the newly forming C-C σ-bonds from the transition state to the product shows a linear correlation with both reaction Gibbs free energies and reverse energy barriers. There is evidence for a similar correlation in other intramolecular Diels–Alder reactions involving non-aromatic dienes. No such correlation is found for intermolecular Diels–Alder reactions. Full article
(This article belongs to the Special Issue Cycloaddition Chemistry)
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Open AccessArticle Design and Synthesis of Thiazolo[5,4-f]quinazolines as DYRK1A Inhibitors, Part I
Molecules 2014, 19(10), 15546-15571; doi:10.3390/molecules191015546
Received: 29 July 2014 / Revised: 19 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 12 | PDF Full-text (960 KB) | HTML Full-text | XML Full-text
Abstract
The convenient synthesis of a library of novel 6,6,5-tricyclic thiazolo[5,4-f] quinazolines (forty molecules) was achieved mainly under microwave irradiation. Dimroth rearrangement and 4,5-dichloro-1,2,3,-dithiazolium chloride (Appel salt) chemistry were associated for the synthesis of a novel 6-aminobenzo[d]thiazole-2,7-dicarbonitrile (16)
[...] Read more.
The convenient synthesis of a library of novel 6,6,5-tricyclic thiazolo[5,4-f] quinazolines (forty molecules) was achieved mainly under microwave irradiation. Dimroth rearrangement and 4,5-dichloro-1,2,3,-dithiazolium chloride (Appel salt) chemistry were associated for the synthesis of a novel 6-aminobenzo[d]thiazole-2,7-dicarbonitrile (16) a versatile molecular platform for the synthesis of various bioactive derivatives. Kinase inhibition of the final compounds was evaluated on a panel of four Ser/Thr kinases (DYRK1A, CDK5, CK1 and GSK3) chosen for their strong implications in various regulation processes, especially Alzheimer’s disease (AD). In view of the results of this preliminary screening, thiazolo[5,4-f]quinazoline scaffolds constitutes a promising source of inspiration for the synthesis of novel bioactive molecules. Among the compounds of this novel chemolibrary, 7i, 8i and 9i inhibited DYRK1A with IC50 values ranging in the double-digit nanomolar range (40, 47 and 50 nM, respectively). Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessArticle Development of an Advanced Synthetic Route to Macrosphelides and Its Application to the Discovery of a More Potent Macrosphelide Derivative
Molecules 2014, 19(10), 15572-15583; doi:10.3390/molecules191015572
Received: 12 August 2014 / Revised: 22 September 2014 / Accepted: 24 September 2014 / Published: 29 September 2014
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Abstract
The discovery of a more cytotoxic macrosphelide derivative, including its total synthesis and bioassay are described. Application of the Koide protocol to a readily available propagylic alcohol allowed the rapid and practical synthesis of a macrosphelide A skeleton. This strategy enabled the successful
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The discovery of a more cytotoxic macrosphelide derivative, including its total synthesis and bioassay are described. Application of the Koide protocol to a readily available propagylic alcohol allowed the rapid and practical synthesis of a macrosphelide A skeleton. This strategy enabled the successful improvement of the cytotoxic activity of the macrosphelide derivative. Full article
(This article belongs to the Special Issue Heterocyclic and Medicinal Chemistry)
Open AccessArticle Anti-Fibrosis Effect of Scutellarin via Inhibition of Endothelial–Mesenchymal Transition on Isoprenaline-Induced Myocardial Fibrosis in Rats
Molecules 2014, 19(10), 15611-15623; doi:10.3390/molecules191015611
Received: 22 July 2014 / Revised: 14 September 2014 / Accepted: 15 September 2014 / Published: 29 September 2014
Cited by 13 | PDF Full-text (1882 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Scutellarin (SCU) is the major active component of breviscapine and has been reported to be capable of decreasing myocardial fibrosis. The aim of the present study is to investigate whether SCU treatment attenuates isoprenaline-induced myocardial fibrosis and the mechanisms of its action. Rats
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Scutellarin (SCU) is the major active component of breviscapine and has been reported to be capable of decreasing myocardial fibrosis. The aim of the present study is to investigate whether SCU treatment attenuates isoprenaline-induced myocardial fibrosis and the mechanisms of its action. Rats were injected subcutaneously with isoprenaline (Iso) to induce myocardial fibrosis and rats in the SCU treatment groups were intraperitoneally infused with SCU (10 mg·kg−1·d−1 or 20 mg·kg−1·d−1, for 14 days). Post-treatment, cardiac functional measurements and the left and right ventricular weight indices (LVWI and RVWI, respectively) were analysed. Pathological alteration, expression of type I and III collagen, Von Willebrand factor, α-smooth muscle actin, cluster of differentiation-31 (CD31), and the Notch signalling proteins (Notch1, Jagged1 and Hes1) were examined. The administration of SCU resulted in a significant improvement in cardiac function and decrease in the cardiac weight indices; reduced fibrous tissue proliferation; reduced levels of type I and III collagen; increased microvascular density; and decreased expression of α-smooth muscle actin and increased expression of CD31, Notch1, Jagged1 and Hes1 in isoprenaline-induced myocardial fibrosis in rats. Our results suggest that SCU prevents isoprenaline-induced myocardial fibrosis via inhibition of cardiac endothelial-mesenchymal transition potentially, which may be associated with the Notch pathway. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Anti-Inflammatory Effect of 3-O-[(6'-O-Palmitoyl)-β-D-glucopyranosyl Sitosterol] from Agave angustifolia on Ear Edema in Mice
Molecules 2014, 19(10), 15624-15637; doi:10.3390/molecules191015624
Received: 11 June 2014 / Revised: 11 September 2014 / Accepted: 12 September 2014 / Published: 29 September 2014
Cited by 6 | PDF Full-text (1820 KB) | HTML Full-text | XML Full-text
Abstract
In Mexico Agave angustifolia has traditionally been used to treat inflammation. The aim of this study was to measure the anti-inflammatory effect of the extract of A. angustifolia, the isolation and identification of active compounds. From the acetone extract two active fractions
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In Mexico Agave angustifolia has traditionally been used to treat inflammation. The aim of this study was to measure the anti-inflammatory effect of the extract of A. angustifolia, the isolation and identification of active compounds. From the acetone extract two active fractions were obtained, (AsF13 and AaF16). For the characterization of pharmacological activity, the acute inflammatory model of mouse ear edema induced with TPA was used. The tissue exposed to TPA and treatments were subjected to two analysis, cytokine quantification (IL-1β, IL-6, IL-10 and TNF-α) and histopathological evaluation. The active fraction (AaF16) consisted principally of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranpsyl] sitosterol. In AaF13 fraction was identified β-sitosteryl glucoside (2) and stigmasterol (3). The three treatments tested showed a concentration-dependent anti-inflammatory effect (AaAc Emax = 33.10%, EC50 = 0.126 mg/ear; AaF13 Emax = 54.22%, EC50 = 0.0524 mg/ear; AaF16 Emax = 61.01%, EC50 = 0.050 mg/ear). The application of TPA caused a significant increase on level of IL-1β, IL-6 and TNFα compared with basal condition, which was countered by any of the experimental treatments. Moreover, the experimental treatments induced a significant increase in the levels of IL-4 and IL-10, compared to the level observed when stimulated with TPA. Therefore, the anti-inflammatory effect of Agave angustifolia, is associated with the presence of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranosyl] sitosterol. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Eckol Enhances Heme Oxygenase-1 Expression through Activation of Nrf2/JNK Pathway in HepG2 Cells
Molecules 2014, 19(10), 15638-15652; doi:10.3390/molecules191015638
Received: 29 July 2014 / Revised: 13 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 18 | PDF Full-text (1179 KB) | HTML Full-text | XML Full-text
Abstract
Eckol isolated from Ecklonia stolonifera was previously reported to exhibit cytoprotective activity with its intrinsic antioxidant activity in in vitro studies. In this study, we characterized the mechanism underlying the eckol-mediated the expression of heme oxygenase-1 (HO-1). Eckol suppressed the production of intracellular
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Eckol isolated from Ecklonia stolonifera was previously reported to exhibit cytoprotective activity with its intrinsic antioxidant activity in in vitro studies. In this study, we characterized the mechanism underlying the eckol-mediated the expression of heme oxygenase-1 (HO-1). Eckol suppressed the production of intracellular reactive oxygen species and increased glutathione level in HepG2 cells. Eckol treatment enhanced the expression of HO-1 at the both level of protein and mRNA in HepG2 cells. Enhanced expression of HO-1 by eckol was presumed to be the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2) demonstrated by its nuclear translocation and increased transcriptional activity. c-Jun NH2-terminal kinases (JNKs) and PI3K/Akt contributed to Nrf2-mediated HO-1 expression. These results demonstrate that the eckol-mediated expression of HO-1 in HepG2 cells is regulated by Nrf2 activation via JNK and PI3K/Akt signaling pathways, suggesting that eckol may be used as a natural antioxidant and cytoprotective agent. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity
Molecules 2014, 19(10), 15653-15672; doi:10.3390/molecules191015653
Received: 14 August 2014 / Revised: 14 September 2014 / Accepted: 18 September 2014 / Published: 29 September 2014
Cited by 3 | PDF Full-text (1827 KB) | HTML Full-text | XML Full-text
Abstract
A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and
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A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effects toward Candida spp. In particular, the two derivatives exhibited potent antifungal activities toward the fluconazole-resistant isolate C. albicans 64110, with both having MIC values of 8 µg/mL. In addition, they had significant inhibitory effects toward two Gram-positive bacteria, Staphylococcus aureus UA1758 (compound 31: MIC = 8 µg/mL; compound 42: MIC = 4 µg/mL) and Staphylococcus epidermidis UF843 (compound 31: MIC = 8 µg/mL; compound 42: MIC = 8 µg/mL). The results of an animal experiment indicated that both compounds could improve the survival rate of model mice infected with ATCC 90028 (fluconazole-susceptible isolate). More importantly, the two compounds exhibited notable in vivo effects toward the fluconazole-resistant C. albicans isolate, which is promising with regard to the clinical problem posed by fluconazole-resistant Candida species. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Combined Mass Spectrometry-Based Metabolite Profiling of Different Pigmented Rice (Oryza sativa L.) Seeds and Correlation with Antioxidant Activities
Molecules 2014, 19(10), 15673-15686; doi:10.3390/molecules191015673
Received: 8 August 2014 / Revised: 26 September 2014 / Accepted: 27 September 2014 / Published: 29 September 2014
Cited by 17 | PDF Full-text (1165 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nine varieties of pigmented rice (Oryza sativa L.) seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography (GC) TOF-MS, to measure antioxidant activities. Clear grouping patterns determined
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Nine varieties of pigmented rice (Oryza sativa L.) seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography (GC) TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA) derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD) and Ilpoom (IP) species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Recent Advances in the Synthesis of Thiophene Derivatives by Cyclization of Functionalized Alkynes
Molecules 2014, 19(10), 15687-15719; doi:10.3390/molecules191015687
Received: 28 August 2014 / Revised: 19 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 26 | PDF Full-text (869 KB) | HTML Full-text | XML Full-text
Abstract
This review is intended to highlight some recent and particularly interesting examples of the synthesis of thiophene derivatives by heterocyclization of readily available S-containing alkyne substrates. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Phytochemical Analysis of Pfaffia glomerata Inflorescences by LC-ESI-MS/MS
Molecules 2014, 19(10), 15720-15734; doi:10.3390/molecules191015720
Received: 4 August 2014 / Revised: 15 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 17 | PDF Full-text (998 KB) | HTML Full-text | XML Full-text
Abstract
Pfaffia glomerata contains high levels of β-ecdysone, which has shown a range of beneficial pharmacological effects. The present study demonstrated that inflorescences of P. glomerata contain other important bioactive compounds in addition to β-ecdysone. The identification of compounds from inflorescences using liquid chromatography
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Pfaffia glomerata contains high levels of β-ecdysone, which has shown a range of beneficial pharmacological effects. The present study demonstrated that inflorescences of P. glomerata contain other important bioactive compounds in addition to β-ecdysone. The identification of compounds from inflorescences using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was performed for the first time. The eight compounds identified were β-ecdysone, flavonoid glycosides such as quercetin-3-O-glucoside, kaempferol-3-O-glucoside and kaempferol-3-O-(6-p-coumaroyl)-glucoside, oleanane-type triterpenoid saponins such as ginsenoside Ro and chikusetsusaponin IV, in addition to oleanonic acid and gluconic acid. This study provided information on the phytochemicals contained in P. glomerata inflorescences revealing the potential application of this plant part as raw material for the phytotherapeutic and cosmetic industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Multi-Scale Computational Study on the Mechanism of Streptococcus pneumoniae Nicotinamidase (SpNic)
Molecules 2014, 19(10), 15735-15753; doi:10.3390/molecules191015735
Received: 28 August 2014 / Revised: 20 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 6 | PDF Full-text (2441 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nicotinamidase (Nic) is a key zinc-dependent enzyme in NAD metabolism that catalyzes the hydrolysis of nicotinamide to give nicotinic acid. A multi-scale computational approach has been used to investigate the catalytic mechanism, substrate binding and roles of active site residues of Nic from
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Nicotinamidase (Nic) is a key zinc-dependent enzyme in NAD metabolism that catalyzes the hydrolysis of nicotinamide to give nicotinic acid. A multi-scale computational approach has been used to investigate the catalytic mechanism, substrate binding and roles of active site residues of Nic from Streptococcus pneumoniae (SpNic). In particular, density functional theory (DFT), molecular dynamics (MD) and ONIOM quantum mechanics/molecular mechanics (QM/MM) methods have been employed. The overall mechanism occurs in two stages: (i) formation of a thioester enzyme-intermediate (IC2) and (ii) hydrolysis of the thioester bond to give the products. The polar protein environment has a significant effect in stabilizing reaction intermediates and in particular transition states. As a result, both stages effectively occur in one step with Stage 1, formation of IC2, being rate limiting barrier with a cost of 53.5 kJ•mol−1 with respect to the reactant complex, RC. The effects of dispersion interactions on the overall mechanism were also considered but were generally calculated to have less significant effects with the overall mechanism being unchanged. In addition, the active site lysyl (Lys103) is concluded to likely play a role in stabilizing the thiolate of Cys136 during the reaction. Full article
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Open AccessArticle Design, Synthesis and SAR Studies of NAD Analogues as Potent Inhibitors towards CD38 NADase
Molecules 2014, 19(10), 15754-15767; doi:10.3390/molecules191015754
Received: 25 July 2014 / Revised: 22 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 16 | PDF Full-text (825 KB) | HTML Full-text | XML Full-text
Abstract
Nicotinamide adenine dinucleotide (NAD), one of the most important coenzymes in the cells, is a substrate of the signaling enzyme CD38, by which NAD is converted to a second messenger, cyclic ADP-ribose, which releases calcium from intracellular calcium stores. Starting with 2′-deoxy-2′-fluoroarabinosyl-β-nicotinamide adenine
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Nicotinamide adenine dinucleotide (NAD), one of the most important coenzymes in the cells, is a substrate of the signaling enzyme CD38, by which NAD is converted to a second messenger, cyclic ADP-ribose, which releases calcium from intracellular calcium stores. Starting with 2′-deoxy-2′-fluoroarabinosyl-β-nicotinamide adenine dinucleotide (ara-F NAD), a series of NAD analogues were synthesized and their activities to inhibit CD38 NAD glycohydrolase (NADase) were evaluated. The adenosine-modified analogues showed potent inhibitory activities, among which 2′-deoxy-2′-fluoroarabinosyl-β-nicotinamide guanine dinucleotide (ara-F NGD) was the most effective one. The structure-activity relationship of NAD analogues was also discussed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Immobilization of Horseradish Peroxidase on NH2-Modified Magnetic Fe3O4/SiO2 Particles and Its Application in Removal of 2,4-Dichlorophenol
Molecules 2014, 19(10), 15768-15782; doi:10.3390/molecules191015768
Received: 14 May 2014 / Revised: 9 August 2014 / Accepted: 7 September 2014 / Published: 29 September 2014
Cited by 37 | PDF Full-text (1766 KB) | HTML Full-text | XML Full-text
Abstract
Fe3O4 nanoparticles were prepared by a co-precipitation method with the assistance of ultrasound irradiation, and then coated with silica generated by hydrolysis and condensation of tetraethoxysilane. The silica-coated Fe3O4 nanoparticles were further modified with 3-aminopropyltriethoxysilane, resulting in
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Fe3O4 nanoparticles were prepared by a co-precipitation method with the assistance of ultrasound irradiation, and then coated with silica generated by hydrolysis and condensation of tetraethoxysilane. The silica-coated Fe3O4 nanoparticles were further modified with 3-aminopropyltriethoxysilane, resulting in anchoring of primary amine groups on the surface of the particles. Horseradish peroxidase (HRP) was then immobilized on the magnetic core-shell particles by using glutaraldehyde as a crosslinking agent. Immobilization conditions were optimized to obtain the highest relative activity of the immobilized enzyme. It was found the durability of the immobilized enzyme to heating and pH variation were improved in comparison with free HRP. The apparent Michaelis constants of the immobilized HRP and free HRP with substrate were compared, showing that the enzyme activity of the immobilized HRP was close to that of free HRP. The HRP immobilized particles, as an enzyme catalyst, were used to activate H2O2 for degrading 2,4-dichlorophenol. The rapid degradation of 2,4-dichlorophenol indicated that the immobilized enzyme has potential applications for removing organic pollutants. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
Open AccessArticle Pinocembrin Protects the Brain against Ischemia-Reperfusion Injury and Reverses the Autophagy Dysfunction in the Penumbra Area
Molecules 2014, 19(10), 15786-15798; doi:10.3390/molecules191015786
Received: 31 July 2014 / Revised: 6 September 2014 / Accepted: 15 September 2014 / Published: 30 September 2014
Cited by 12 | PDF Full-text (2692 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate the effects of pinocembrin on brain ischemia/reperfusion (I/R) injury and the potential involvement of autophagy activity changes in the penumbra area in the mechanisms of pinocembrin activity. Focal cerebral I/R model was induced by middle
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The aim of this study was to investigate the effects of pinocembrin on brain ischemia/reperfusion (I/R) injury and the potential involvement of autophagy activity changes in the penumbra area in the mechanisms of pinocembrin activity. Focal cerebral I/R model was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h reperfusion. Pinocembrin was administered intravenously at different doses (1, 3, and 10 mg/kg, respectively) at the onset of reperfusion. Neurological function, brain infarction and brain swelling ratio were evaluated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and immunohistochemical analysis (Caspase-3) were used to evaluate apoptosis in the penumbra cortex. Two key proteins of autophagy, LC3B and Beclin1, were detected by western blot. The results showed that pinocembrin-treatment could significantly reduce neurological deficit scores, infarct volume, cerebral edema and improve pathological lesion in the I/R rats. Pinocembrin-treatment could also reduce the number of TUNEL-positive and Caspase-3-positive neurons, and upregulate the expression of LC3B and Beclin1 in penumbra area. These results suggested that pinocembrin could protect the brain against I/R injury, and the possible mechanisms might be attributed to inhibition of apoptosis and reversed autophagy activity in penumbra area. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle New Derivatives of 3,4-Dihydroisoquinoline-3-carboxylic Acid with Free-Radical Scavenging, D-Amino Acid Oxidase, Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activity
Molecules 2014, 19(10), 15866-15890; doi:10.3390/molecules191015866
Received: 14 August 2014 / Revised: 17 September 2014 / Accepted: 22 September 2014 / Published: 30 September 2014
Cited by 3 | PDF Full-text (2460 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·−) and nitric oxide radical (·NO) assays. We
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A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·−) and nitric oxide radical (·NO) assays. We also studied D-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Photochemical Aryl Radical Cyclizations to Give (E)-3-Ylideneoxindoles
Molecules 2014, 19(10), 15891-15899; doi:10.3390/molecules191015891
Received: 2 September 2014 / Revised: 19 September 2014 / Accepted: 24 September 2014 / Published: 30 September 2014
Cited by 2 | PDF Full-text (815 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
(E)-3-Ylideneoxindoles are prepared in methanol in reasonable to good yields, as adducts of photochemical 5-exo-trig of aryl radicals, in contrast to previously reported analogous radical cyclizations initiated by tris(trimethylsilyl)silane and azo-initiators that gave reduced oxindole adducts. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessArticle New Water-Soluble Carbamate Ester Derivatives of Resveratrol
Molecules 2014, 19(10), 15900-15917; doi:10.3390/molecules191015900
Received: 27 August 2014 / Revised: 22 September 2014 / Accepted: 24 September 2014 / Published: 1 October 2014
Cited by 12 | PDF Full-text (416 KB) | HTML Full-text | XML Full-text
Abstract
Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism
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Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of carbamate ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol)-350 (mPEG-350) or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport. Full article
(This article belongs to the Special Issue Resveratrol)
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Open AccessArticle Stereoselective Synthesis and Cytoselective Toxicity of Monoterpene-Fused 2-Imino-1,3-thiazines
Molecules 2014, 19(10), 15918-15937; doi:10.3390/molecules191015918
Received: 27 August 2014 / Revised: 22 September 2014 / Accepted: 24 September 2014 / Published: 2 October 2014
Cited by 3 | PDF Full-text (1441 KB) | HTML Full-text | XML Full-text
Abstract
Starting from pinane-, apopinane- and carane-based 1,3-amino alcohols obtained from monoterpene-based β-amino acids, a library of monoterpene-fused 2-imino-1,3-thiazines as main products and 2-thioxo-1,3-oxazines as side-products were prepared via two- or three-step syntheses. When thiourea adducts prepared from 1,3-amino alcohols and aryl isothiocyanates were
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Starting from pinane-, apopinane- and carane-based 1,3-amino alcohols obtained from monoterpene-based β-amino acids, a library of monoterpene-fused 2-imino-1,3-thiazines as main products and 2-thioxo-1,3-oxazines as side-products were prepared via two- or three-step syntheses. When thiourea adducts prepared from 1,3-amino alcohols and aryl isothiocyanates were reacted with CDI under mild conditions, O-imidazolylcarbonyl intermediates were isolated which could be transformed to the desired 1,3-thiazines under microwave conditions. 1,3-Thiazines and 2-thioxo-1,3-oxazine side-products could also be prepared in one-step reactions through the application of CDI and microwave irradiation. The ring-closure process was extended to cycloalkane-based γ-hydroxythioureas. The carane- and apopinane-based derivatives exhibited marked antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, A2780, MCF7 and A431). Full article
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Open AccessArticle Lessons from Chlorophylls: Modifications of Porphyrinoids Towards Optimized Solar Energy Conversion
Molecules 2014, 19(10), 15938-15954; doi:10.3390/molecules191015938
Received: 21 April 2014 / Revised: 20 August 2014 / Accepted: 5 September 2014 / Published: 3 October 2014
Cited by 9 | PDF Full-text (582 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Practical applications of photosynthesis-inspired processes depend on a thorough understanding of the structures and physiochemical features of pigment molecules such as chlorophylls and bacteriochlorophylls. Consequently, the major structural features of these pigments have been systematically examined as to how they influence the S
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Practical applications of photosynthesis-inspired processes depend on a thorough understanding of the structures and physiochemical features of pigment molecules such as chlorophylls and bacteriochlorophylls. Consequently, the major structural features of these pigments have been systematically examined as to how they influence the S1 state energy, lifetimes, quantum yields, and pigment photostability. In particular, the effects of the macrocyclic π-electron system, central metal ion (CMI), peripheral substituents, and pigment aggregation, on these critical parameters are discussed. The results obtained confirm that the π-electron system of the chromophore has the greatest influence on the light energy conversion capacity of porphyrinoids. Its modifications lead to changes in molecular symmetry, which determine the energy levels of frontier orbitals and hence affect the S1 state properties. In the case of bacteriochlorophylls aggregation can also strongly decrease the S1 energy. The CMI may be considered as another influential structural feature which only moderately influences the ground-state properties of bacteriochlorophylls but strongly affects the singlet excited-state. An introduction of CMIs heavier than Mg2+ significantly improves pigments' photostabilities, however, at the expense of S1 state lifetime. Modifications of the peripheral substituents may also influence the S1 energy, and pigments’ redox potentials, which in turn influence their photostability. Full article
(This article belongs to the Special Issue Macrocyclic Chemistry)
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Open AccessArticle Synthesis of New Perhydropyrrolo[1,2-a]pyrazine Derivatives and Their Evaluation in Animal Models of Epilepsy
Molecules 2014, 19(10), 15955-15981; doi:10.3390/molecules191015955
Received: 20 August 2014 / Revised: 24 September 2014 / Accepted: 26 September 2014 / Published: 7 October 2014
PDF Full-text (680 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel stereochemically pure derivatives of the investigative broad-spectrum anticonvulsant ADD408003 was designed and synthesized. Five-center four-component (U-5C-4CR) and four-center three-component (U-4C-3CR) variants of Ugi reaction were used in the key step of the synthetic pathways. The compounds obtained were evaluated
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A series of novel stereochemically pure derivatives of the investigative broad-spectrum anticonvulsant ADD408003 was designed and synthesized. Five-center four-component (U-5C-4CR) and four-center three-component (U-4C-3CR) variants of Ugi reaction were used in the key step of the synthetic pathways. The compounds obtained were evaluated for the anticonvulsant activitiy in the maximal electroshock seizure (MES), subcutaneous Metrazole (scMET) and minimal clonic seizure (6 Hz) animal models of epilepsy. The efficacies of most derivatives in the 6 Hz model of pharmacoresistant partial seizures were markedly higher than in the ‘classical’ MES and scMET models. The most active compounds, (4R,8aR)-3a, and (4S,8aS)-6 displayed median effective doses (ED50) of 47.90 and 126.19 mg/kg, respectively, for the 6 Hz test. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Efficient Biotransformation of Polysialogangliosides for Preparation of GM1 by Cellulosimicrobium sp. 21
Molecules 2014, 19(10), 16001-16012; doi:10.3390/molecules191016001
Received: 1 September 2014 / Revised: 28 September 2014 / Accepted: 29 September 2014 / Published: 8 October 2014
Cited by 1 | PDF Full-text (2528 KB) | HTML Full-text | XML Full-text
Abstract
A new ganglioside transformed strain isolated from soil was identified as Cellulosimicrobium sp. 21. It produced a sialidase which transformed polysialo-gangliosides GD1 and GT1 into a monosialoterahexosylganglioside, i.e., ganglioside GM1. The sialidase had both NeuAc-α-2,3- and NeuAc-α-2,8-sialidase activity without producing asiolo-GM1. The
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A new ganglioside transformed strain isolated from soil was identified as Cellulosimicrobium sp. 21. It produced a sialidase which transformed polysialo-gangliosides GD1 and GT1 into a monosialoterahexosylganglioside, i.e., ganglioside GM1. The sialidase had both NeuAc-α-2,3- and NeuAc-α-2,8-sialidase activity without producing asiolo-GM1. The optimum conditions were evaluated and it was found that the transformation was optimally performed at 30 °C and pH 7.0. The substrate should be added at the beginning of the reaction and the concentration of substrate was 3% (w/v). Under these optimum conditions, Cellulosimicrobium sp. 21 converted GD1 and GT1 into GM1 in inorganic medium in a 5 L bioreactor with the recovery rate of 69.3%. The product contained 50.3% GM1 and was purified on silica to give the product with 95% of GM1 with a recovery rate of 30.5%. Therefore, Cellulosimicrobium sp. 21 has potential to be applied in the production of GM1 in the pharmaceutical industry. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Ethanolic Extract of Taheebo Attenuates Increase in Body Weight and Fatty Liver in Mice Fed a High-Fat Diet
Molecules 2014, 19(10), 16013-16023; doi:10.3390/molecules191016013
Received: 2 September 2014 / Revised: 26 September 2014 / Accepted: 29 September 2014 / Published: 8 October 2014
Cited by 6 | PDF Full-text (2728 KB) | HTML Full-text | XML Full-text
Abstract
We evaluated whether intake of an ethanolic extract of Taheebo (TBE) from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD)-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w) for 11
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We evaluated whether intake of an ethanolic extract of Taheebo (TBE) from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD)-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w) for 11 weeks. The diet of control (HFD) mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage); the diet of experimental (TBE) mice was supplemented with TBE (150 mg/kg body weight/day by gavage). Mice administered TBE had significantly reduced body weight gain, fat accumulation in the liver, and fat pad weight, compared to HFD mice. Reduced hypertrophy of fat cells was also observed in TBE mice. Mice administered TBE also showed significantly lower serum levels of triglycerides, insulin, and leptin. Lipid profiles and levels of mRNAs and proteins related to lipid metabolism were determined in liver and white adipose tissue of the mice. Expression of mRNA and proteins related to lipogenesis were decreased in TBE-administered mice compared to mice fed HFD alone. These results suggest that TBE inhibits obesity and fat accumulation by regulation of gene expression related to lipid metabolism in HFD-induced obesity in mice. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Epoxidized Vegetable Oils Plasticized Poly(lactic acid) Biocomposites: Mechanical, Thermal and Morphology Properties
Molecules 2014, 19(10), 16024-16038; doi:10.3390/molecules191016024
Received: 25 July 2014 / Revised: 21 September 2014 / Accepted: 22 September 2014 / Published: 8 October 2014
Cited by 28 | PDF Full-text (2300 KB) | HTML Full-text | XML Full-text
Abstract
Plasticized poly(lactic acid) PLA with epoxidized vegetable oils (EVO) were prepared using a melt blending method to improve the ductility of PLA. The plasticization of the PLA with EVO lowers the Tg as well as cold-crystallization temperature. The tensile properties demonstrated that
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Plasticized poly(lactic acid) PLA with epoxidized vegetable oils (EVO) were prepared using a melt blending method to improve the ductility of PLA. The plasticization of the PLA with EVO lowers the Tg as well as cold-crystallization temperature. The tensile properties demonstrated that the addition of EVO to PLA led to an increase of elongation at break, but a decrease of tensile modulus. Plasticized PLA showed improvement in the elongation at break by 2058% and 4060% with the addition of 5 wt % epoxidized palm oil (EPO) and mixture of epoxidized palm oil and soybean oil (EPSO), respectively. An increase in the tensile strength was also observed in the plasticized PLA with 1 wt % EPO and EPSO. The use of EVO increases the mobility of the polymeric chains, thereby improving the flexibility and plastic deformation of PLA. The SEM micrograph of the plasticized PLA showed good compatible morphologies without voids resulting from good interfacial adhesion between PLA and EVO. Based on the results of this study, EVO may be used as an environmentally friendly plasticizer that can improve the overall properties of PLA. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Characterization and Quantification of the Compounds of the Ethanolic Extract from Caesalpinia ferrea Stem Bark and Evaluation of Their Mutagenic Activity
Molecules 2014, 19(10), 16039-16057; doi:10.3390/molecules191016039
Received: 30 June 2014 / Revised: 23 September 2014 / Accepted: 23 September 2014 / Published: 8 October 2014
Cited by 10 | PDF Full-text (1757 KB) | HTML Full-text | XML Full-text
Abstract
Caesalpinia ferrea Martius has traditionally been used in Brazil for many medicinal purposes, such as the treatment of bronchitis, diabetes and wounds. Despite its use as a medicinal plant, there is still no data regarding the genotoxic effect of the stem bark. This
[...] Read more.
Caesalpinia ferrea Martius has traditionally been used in Brazil for many medicinal purposes, such as the treatment of bronchitis, diabetes and wounds. Despite its use as a medicinal plant, there is still no data regarding the genotoxic effect of the stem bark. This present work aims to assess the qualitative and quantitative profiles of the ethanolic extract from the stem bark of C. ferrea and to evaluate its mutagenic activity, using a Salmonella/microsome assay for this species. As a result, a total of twenty compounds were identified by Flow Injection Analysis Electrospray Ionization Ion Trap Mass Spectrometry (FIA-ESI-IT-MS/MSn) in the ethanolic extract from the stem bark of C. ferrea. Hydrolyzable tannins predominated, principally gallic acid derivatives. The HPLC-DAD method was developed for rapid quantification of six gallic acid compounds and ellagic acid derivatives. C. ferrea is widely used in Brazil, and the absence of any mutagenic effect in the Salmonella/microsome assay is important for pharmacological purposes and the safe use of this plant. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis and Sar Study of Diarylpentanoid Analogues as New Anti-Inflammatory Agents
Molecules 2014, 19(10), 16058-16081; doi:10.3390/molecules191016058
Received: 8 August 2014 / Revised: 15 September 2014 / Accepted: 18 September 2014 / Published: 9 October 2014
Cited by 10 | PDF Full-text (1343 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83
[...] Read more.
A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure–activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Studies Regarding As(V) Adsorption from Underground Water by Fe-XAD8-DEHPA Impregnated Resin. Equilibrium Sorption and Fixed-Bed Column Tests
Molecules 2014, 19(10), 16082-16101; doi:10.3390/molecules191016082
Received: 11 July 2014 / Revised: 12 September 2014 / Accepted: 18 September 2014 / Published: 9 October 2014
Cited by 5 | PDF Full-text (770 KB) | HTML Full-text | XML Full-text
Abstract
The characteristics of arsenic adsorption onto Fe-XAD8-DEHPA resin were studied on the laboratory scale using aqueous solutions and natural underground waters. Amberlite XAD8 resin was impregnated with di(2-ethylhexyl) phosphoric acid (DEHPA) via the dry method of impregnation. Fe(III) ions were loaded onto the
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The characteristics of arsenic adsorption onto Fe-XAD8-DEHPA resin were studied on the laboratory scale using aqueous solutions and natural underground waters. Amberlite XAD8 resin was impregnated with di(2-ethylhexyl) phosphoric acid (DEHPA) via the dry method of impregnation. Fe(III) ions were loaded onto the impregnated resin by exploiting the high affinity of arsenic towards iron. The studies were conducted by both in contact and continuous modes. Kinetics data revealed that the removal of arsenic by Fe-XAD8-DEHPA resin is a pseudo-second-order reaction. The equilibrium data were modelled with Freundlich Langmuir and Dubinin Radushkevich (D-R) isotherms and it was found that the Freundlich model give the poorest correlation coefficient. The maximum adsorption capacity obtained from the Langmuir isotherm is 22.6 µg As(V)/g of Fe-XAD8-DEHPA resin. The mean free energy of adsorption was found in this study to be 7.2 kJ/mol and the Δvalue negative (−9.2 kJ/mol). This indicates that the sorption process is exothermal, spontaneous and physical in nature. The studied Fe-XAD8-DEHPA resin showed excellent arsenic removal performance by sorption, both from synthetic solution and the natural water sample, and could be regenerated simply by using aqueous NaOH or HCl solutions. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle State-Dependent Molecular Dynamics
Molecules 2014, 19(10), 16122-16145; doi:10.3390/molecules191016122
Received: 24 July 2014 / Revised: 4 September 2014 / Accepted: 17 September 2014 / Published: 9 October 2014
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Abstract
This paper proposes a new mixed quantum mechanics (QM)—molecular mechanics (MM) approach, where MM is replaced by quantum Hamilton mechanics (QHM), which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of
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This paper proposes a new mixed quantum mechanics (QM)—molecular mechanics (MM) approach, where MM is replaced by quantum Hamilton mechanics (QHM), which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics. Full article
Open AccessArticle Electro-Acupuncture at Neiguan Pretreatment Alters Genome-Wide Gene Expressions and Protects Rat Myocardium against Ischemia-Reperfusion
Molecules 2014, 19(10), 16158-16178; doi:10.3390/molecules191016158
Received: 21 June 2014 / Revised: 12 September 2014 / Accepted: 15 September 2014 / Published: 9 October 2014
Cited by 10 | PDF Full-text (3210 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study investigated genome-wide gene expressions and the cardioprotective effects of electro-acupuncture pretreatment at the PC6 Neiguan acupoint on myocardial ischemia reperfusion (I/R) injury. Male SD rats were randomly divided into four groups: sham operation (SO), I/R, electro-acupuncture at the PC6 Neiguan acupoint
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This study investigated genome-wide gene expressions and the cardioprotective effects of electro-acupuncture pretreatment at the PC6 Neiguan acupoint on myocardial ischemia reperfusion (I/R) injury. Male SD rats were randomly divided into four groups: sham operation (SO), I/R, electro-acupuncture at the PC6 Neiguan acupoint pretreatment (EA) and electro-acupuncture at non-acupoint pretreatment (NA). Compared with the I/R group, the survival rate of the EA group was significantly increased, the arrhythmia score, infarction area, serum concentrations of CK, LDH and CK-Mb and plasma level of cTnT were significantly decreased. RNA-seq results showed that 725 genes were up-regulated and 861 genes were down-regulated under I/R conditions compared to the SO group; both EA and NA reversed some of these gene expression levels (592 in EA and 238 in NA group). KEGG pathway analysis indicated that these genes were involved in multiple pathways, including ECM, MAPK signaling, apoptosis, cytokine and leukocyte pathways. In addition, some pathways were uniquely regulated by EA, but not NA pretreatment, such as oxidative stress, cardiac muscle contraction, gap junction, vascular smooth muscle contraction, hypertrophic, NOD-like receptor, and P53 and B-cell receptor pathways. This study was first to reveal the gene expression signatures of acute myocardial I/R injury and electro-acupuncture pretreatment in rats. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Recombinant Expressed Vector pET32a (+) S Constructed by Ligation Independent Cloning
Molecules 2014, 19(10), 16179-16189; doi:10.3390/molecules191016179
Received: 5 August 2014 / Revised: 9 September 2014 / Accepted: 9 September 2014 / Published: 10 October 2014
Cited by 2 | PDF Full-text (1911 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this work was to develop a new method for constructing vectors, named ligation-independent cloning (LIC) method. We constructed the S label expression vector and recombinant pET32a (+) S-phoN2 by LIC. The recombinant proteins were expressed in E. coli at a
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The aim of this work was to develop a new method for constructing vectors, named ligation-independent cloning (LIC) method. We constructed the S label expression vector and recombinant pET32a (+) S-phoN2 by LIC. The recombinant proteins were expressed in E. coli at a high level, and then the specificity of the recombinant proteins was identified by western blot. The target band was detected by S monoclonal antibody and Apyrase polyclonal antibodies but not Trx monoclonal antibody and HIS monoclonal antibody. Finally, we obtained protein Apyrase in E. coli (BL21), with a protein-only expression S tag. Collectively, our results demonstrated that LIC is effective for the construction of new vectors and recombinant plasmids. Free from the limitations of restriction enzyme sites and with a higher positive rate, LIC processes should find broad applications in molecular biology research. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Structural Elucidation of the DFG-Asp in and DFG-Asp out States of TAM Kinases and Insight into the Selectivity of Their Inhibitors
Molecules 2014, 19(10), 16223-16239; doi:10.3390/molecules191016223
Received: 31 July 2014 / Revised: 24 September 2014 / Accepted: 26 September 2014 / Published: 10 October 2014
Cited by 4 | PDF Full-text (2603 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members
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Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
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Open AccessCommunication Photoregeneration of Trimethylsilyl Cellulose as a Tool for Microstructuring Ultrathin Cellulose Supports
Molecules 2014, 19(10), 16266-16273; doi:10.3390/molecules191016266
Received: 18 August 2014 / Revised: 22 September 2014 / Accepted: 28 September 2014 / Published: 10 October 2014
Cited by 2 | PDF Full-text (886 KB) | HTML Full-text | XML Full-text
Abstract
Microstructured thin films based on cellulose, the most abundant biopolymer on Earth, have been obtained by UV-irradiation of acid-labile trimethylsilyl cellulose thin films in the presence of N-hydroxynaphtalimide triflate as photoacid generator. We demonstrate that this photoregeneration process can be exploited for
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Microstructured thin films based on cellulose, the most abundant biopolymer on Earth, have been obtained by UV-irradiation of acid-labile trimethylsilyl cellulose thin films in the presence of N-hydroxynaphtalimide triflate as photoacid generator. We demonstrate that this photoregeneration process can be exploited for the manufacture of cellulose patterns having feature sizes down to 1 μm, with potential applications in life sciences. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
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Open AccessArticle Exploration of Piperidinols as Potential Antitubercular Agents
Molecules 2014, 19(10), 16274-16290; doi:10.3390/molecules191016274
Received: 14 July 2014 / Revised: 9 September 2014 / Accepted: 24 September 2014 / Published: 10 October 2014
Cited by 6 | PDF Full-text (1074 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Novel drugs to treat tuberculosis are required and the identification of potential targets is important. Piperidinols have been identified as potential antimycobacterial agents (MIC < 5 μg/mL), which also inhibit mycobacterial arylamine N-acetyltransferase (NAT), an enzyme essential for mycobacterial survival inside macrophages.
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Novel drugs to treat tuberculosis are required and the identification of potential targets is important. Piperidinols have been identified as potential antimycobacterial agents (MIC < 5 μg/mL), which also inhibit mycobacterial arylamine N-acetyltransferase (NAT), an enzyme essential for mycobacterial survival inside macrophages. The NAT inhibition involves a prodrug-like mechanism in which activation leads to the formation of bioactive phenyl vinyl ketone (PVK). The PVK fragment selectively forms an adduct with the cysteine residue in the active site. Time dependent inhibition of the NAT enzyme from Mycobacterium marinum (M. marinum) demonstrates a covalent binding mechanism for all inhibitory piperidinol analogues. The structure activity relationship highlights the importance of halide substitution on the piperidinol benzene ring. The structures of the NAT enzymes from M. marinum and M. tuberculosis, although 74% identical, have different residues in their active site clefts and allow the effects of amino acid substitutions to be assessed in understanding inhibitory potency. In addition, we have used the piperidinol 3-dimensional shape and electrostatic properties to identify two additional distinct chemical scaffolds as inhibitors of NAT. While one of the scaffolds has anti-tubercular activity, both inhibit NAT but through a non-covalent mechanism. Full article
(This article belongs to the Special Issue Prodrugs)
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Open AccessArticle LC-MS/MS Determination and Pharmacokinetic Study of Dehydrocorydaline in Rat Plasma after Oral Administration of Dehydrocorydaline and Corydalis yanhusuo Extract
Molecules 2014, 19(10), 16312-16326; doi:10.3390/molecules191016312
Received: 9 July 2014 / Revised: 14 August 2014 / Accepted: 18 September 2014 / Published: 13 October 2014
Cited by 5 | PDF Full-text (375 KB) | HTML Full-text | XML Full-text
Abstract
A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC-MS/MS) was developed and validated for determination of dehydrocorydaline (DHC) in rat plasma using nitidine chloride as an internal standard. The analytes were solid-phase extracted and eluted on a C18 chromatography column using
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A rapid, sensitive and selective liquid chromatography/tandem mass spectrometry method (LC-MS/MS) was developed and validated for determination of dehydrocorydaline (DHC) in rat plasma using nitidine chloride as an internal standard. The analytes were solid-phase extracted and eluted on a C18 chromatography column using a mobile phase of acetonitrile and water (containing 0.8% formic acid and 10 mM ammonium acetate) (28:72, v/v). Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range 0.625–250 ng/mL with a quantification limit of 0.625 ng/mL. The precision was <13.7%, the accuracy >93.1%, and extraction recovery ranged from 92.1% to 107%. The validated method was successfully applied to the pharmacokinetics and excretion study of DHC in rat plasma after oral administration of pure DHC and an effective fraction of Corydalis yanhusuo (EFY). The pharmacokinetic parameters showed that DHC from EFY was absorbed more rapidly and eliminated more slowly than pure DHC. The result suggests that the differences might be due to the presence of P-glycoprotein (P-gp) inhibitors and that other alkaloids co-existing in the EFY may compete with DHC for transportation by P-gp, metabolization by P450, and binding to plasma proteins. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Biological Evaluation of Novel Curcuminoid Derivatives
Molecules 2014, 19(10), 16349-16372; doi:10.3390/molecules191016349
Received: 15 September 2014 / Revised: 26 September 2014 / Accepted: 29 September 2014 / Published: 13 October 2014
PDF Full-text (1015 KB) | HTML Full-text | XML Full-text
Abstract
Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11ah, 15ah and 19ad) with enhanced bioactivity have been synthesized. Among the synthesized
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Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11ah, 15ah and 19ad) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 µM /mL against selected medically important Gram-positive cocci (S. aureus and S. viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 µM. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication The Effect of Freeze/Thaw Cycles on Reproducibility of Metabolic Profiling of Marine Microalgal Extracts Using Direct Infusion High-Resolution Mass Spectrometry (HR-MS)
Molecules 2014, 19(10), 16373-16380; doi:10.3390/molecules191016373
Received: 23 July 2014 / Revised: 3 October 2014 / Accepted: 9 October 2014 / Published: 13 October 2014
Cited by 4 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
During normal sample preparation, storage in freezers and subsequent freeze/thaw cycles are commonly introduced. The effect of freeze/thaw cycles on the metabolic profiling of microalgal extracts using HR-MS was investigated. Methanolic extracts of monocultures of Arctic marine diatoms were analyzed immediately after extraction,
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During normal sample preparation, storage in freezers and subsequent freeze/thaw cycles are commonly introduced. The effect of freeze/thaw cycles on the metabolic profiling of microalgal extracts using HR-MS was investigated. Methanolic extracts of monocultures of Arctic marine diatoms were analyzed immediately after extraction, after seven days of storage at −78 °C (one freeze/thaw cycle), and after additional seven days at −20 °C (two freeze/thaw cycles). Repeated direct infusion high-resolution mass spectrometry analysis of microalgae extracts of the same sample showed that reproducibility was ca. 90% when a fresh (unfrozen) sample was analyzed. The overall reproducibility decreased further by ca. 10% after the first freeze/thaw-cycle, and after one more freeze/thaw cycle the reproducibility decreased further by ca. 7%. The decrease in reproducibility after freeze-thaw cycles could be attributed to sample degradation and not to instrument variability. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Biopharmaceutical Profiling of New Antitumor Pyrazole Derivatives
Molecules 2014, 19(10), 16381-16401; doi:10.3390/molecules191016381
Received: 29 August 2014 / Revised: 26 September 2014 / Accepted: 29 September 2014 / Published: 13 October 2014
Cited by 10 | PDF Full-text (1854 KB) | HTML Full-text | XML Full-text
Abstract
Several new pyrazole derivatives have demonstrated promising antiproliferative and cytotoxic effects, but their poor solubility raised concerns over possible biopharmaceutical limitations. In order to improve their pharmaceutical potential we performed the biopharmaceutical profiling for nine pyrazole compounds using in vitro and computational methods.
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Several new pyrazole derivatives have demonstrated promising antiproliferative and cytotoxic effects, but their poor solubility raised concerns over possible biopharmaceutical limitations. In order to improve their pharmaceutical potential we performed the biopharmaceutical profiling for nine pyrazole compounds using in vitro and computational methods. The experimental solubility was determined in five different media using a validated HPLC method. Although the experimental solubility was lower than the predicted one, a good linear relationship was observed. The results also indicated a minimal impact of endogenous tensioactives on solubility, suggesting dissolution rate limited absorption. The in silico experiments were focused on identification of molecular determinants of solubility, evaluation of drug-likeness, prediction of in vivo absorption based on mechanistic models, as well as identification of the main factors that could impact on the oral bioavailability. The results suggested that dose, solubility and particle size are the main determinants of absorption, whereas permeability has little effect, confirming the BCS Class II behavior of the compounds. The present investigation was able to rank the tested compounds in terms of biopharmaceutical behavior, and indicated the B3 series compounds as having a more favorable absorption profile making them the main candidates for advance to the pre-clinical in vivo studies. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Characterization and Development of EST-SSR Markers Derived from Transcriptome of Yellow Catfish
Molecules 2014, 19(10), 16402-16415; doi:10.3390/molecules191016402
Received: 6 August 2014 / Revised: 28 September 2014 / Accepted: 29 September 2014 / Published: 13 October 2014
Cited by 9 | PDF Full-text (1752 KB) | HTML Full-text | XML Full-text
Abstract
Yellow catfish (Pelteobagrus fulvidraco) is one of the most important freshwater fish due to its delicious flesh and high nutritional value. However, lack of sufficient simple sequence repeat (SSR) markers has hampered the progress of genetic selection breeding and molecular research
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Yellow catfish (Pelteobagrus fulvidraco) is one of the most important freshwater fish due to its delicious flesh and high nutritional value. However, lack of sufficient simple sequence repeat (SSR) markers has hampered the progress of genetic selection breeding and molecular research for yellow catfish. To this end, we aimed to develop and characterize polymorphic expressed sequence tag (EST)–SSRs from the 454 pyrosequencing transcriptome of yellow catfish. Totally, 82,794 potential EST-SSR markers were identified and distributed in the coding and non-coding regions. Di-nucleotide (53,933) is the most abundant motif type, and AC/GT, AAT/ATT, AAAT/ATTT are respective the most frequent di-, tri-, tetra-nucleotide repeats. We designed primer pairs for all of the identified EST-SSRs and randomly selected 300 of these pairs for further validation. Finally, 263 primer pairs were successfully amplified and 57 primer pairs were found to be consistently polymorphic when four populations of 48 individuals were tested. The number of alleles for the 57 loci ranged from 2 to 17, with an average of 8.23. The observed heterozygosity (HO), expected heterozygosity (HE), polymorphism information content (PIC) and fixation index (fis) values ranged from 0.04 to 1.00, 0.12 to 0.92, 0.12 to 0.91 and −0.83 to 0.93, respectively. These EST-SSR markers generated in this study could greatly facilitate future studies of genetic diversity and molecular breeding in yellow catfish. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Optimization of Extraction Conditions of Areca Seed Polyphenols and Evaluation of Their Antioxidant Activities
Molecules 2014, 19(10), 16416-16427; doi:10.3390/molecules191016416
Received: 21 August 2014 / Revised: 9 October 2014 / Accepted: 9 October 2014 / Published: 13 October 2014
Cited by 8 | PDF Full-text (598 KB) | HTML Full-text | XML Full-text
Abstract
Polyphenols are functional compounds in plants, which possess many bioactivities beneficial for humans. The aim of this study was to establish a highly efficient method for extracting polyphenol compounds from areca seeds and further to identify polyphenols and antioxidant properties of the seeds.
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Polyphenols are functional compounds in plants, which possess many bioactivities beneficial for humans. The aim of this study was to establish a highly efficient method for extracting polyphenol compounds from areca seeds and further to identify polyphenols and antioxidant properties of the seeds. A quadratic general rotary unitized design was used to determine the optimal extraction process. The polyphenols were identified using LC-TOF-MS. By comparison with ascorbic acid (Vc), the antioxidant activities of the ethanol extracts were evaluated using three complementary in vitro assays: inhibition of the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging activity, hydroxyl radical-scavenging activity, and reducing ability. The two major polyphenols obtained were epicatechin and syringic acid. The ethanol extracts of areca seeds showed significantly greater antioxidant activity (p < 0.05) than Vc using the DPPH and reducing power assay, but lower ability (p < 0.05) using the hydroxyl radical assay. The results indicate that the areca seed is an excellent food material with potential antioxidant properties. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Stumps of Eucalyptus globulus as a Source of Antioxidant and Antimicrobial Polyphenols
Molecules 2014, 19(10), 16428-16446; doi:10.3390/molecules191016428
Received: 1 September 2014 / Revised: 29 September 2014 / Accepted: 10 October 2014 / Published: 13 October 2014
Cited by 15 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text
Abstract
These past years have seen an enormous development of the area of natural antioxidants and antimicrobials. Eucalyptus globulus is widely cultivated in subtropical and Mediterranean regions in intensive short rotation coppice plantations. In the Portuguese context, E. globulus is the third species in
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These past years have seen an enormous development of the area of natural antioxidants and antimicrobials. Eucalyptus globulus is widely cultivated in subtropical and Mediterranean regions in intensive short rotation coppice plantations. In the Portuguese context, E. globulus is the third species in terms of forest area. The stump is the basal part of the tree, including the near-the-ground stem portion and the woody roots that remain after stem felling. The purpose of this work was to study the phytochemical profile and to evaluate the antioxidant and antimicrobial properties of several crude stump wood and stump bark extracts of E. globulus, comparing it with similar extracts of E. globulus wood (industrial chips). The results showed the presence of high concentrations of total phenolic compounds (>200 mg GAE/g extract) and flavonoids (>10 mg QE/g extract) in E. globulus stump extracts. Generally the stump wood extracts stands out from the other ones, presenting the highest percentages of inhibition of linoleic acid oxidation. It was also possible to conclude that the extracts were more active against Gram-positive bacteria, presenting low MIC values. This study thus provides information supporting the economic valorization of E. globulus stump wood. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Synthesis, Crystal Structure, and Biological Evaluation of a Series of Phloretin Derivatives
Molecules 2014, 19(10), 16447-16457; doi:10.3390/molecules191016447
Received: 12 August 2014 / Revised: 10 September 2014 / Accepted: 23 September 2014 / Published: 13 October 2014
Cited by 4 | PDF Full-text (519 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A one-step synthesis of phloretin derivatives 211 from phloretin in good to excellent yields is reported. Their structures were characterized by 1H-NMR, 13C-NMR and MS, and the structures of 8 and 11 were determined by X-ray diffraction analysis. A
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A one-step synthesis of phloretin derivatives 211 from phloretin in good to excellent yields is reported. Their structures were characterized by 1H-NMR, 13C-NMR and MS, and the structures of 8 and 11 were determined by X-ray diffraction analysis. A mechanism for the formation of 911 is proposed. Compared with the anticancer drug docetaxel, phloretin, phloretin derivatives and phlorizin exhibited moderate cytotoxicity toward the MDA-MB-231, SPC-A1, A549, MCF-7 and EC109 cell lines. Among all of the tested compounds, 7 exhibited the strongest cytotoxicity toward the five cell lines and was more active than docetaxel in MDA-MB-231 cells. Our findings suggest that these derivatives hold great promise for further development as anticancer agents. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Design of Composite Photocatalyst of TiO2 and Y-Zeolite for Degradation of 2-Propanol in the Gas Phase under UV and Visible Light Irradiation
Molecules 2014, 19(10), 16477-16488; doi:10.3390/molecules191016477
Received: 4 August 2014 / Revised: 22 September 2014 / Accepted: 30 September 2014 / Published: 13 October 2014
Cited by 7 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text
Abstract
Hydrophobic Y-zeolite (SiO2/Al2O3 = 810) and TiO2 composite photocatalysts were designed by using two different types of TiO2 precursors, i.e., titanium ammonium oxalate and ammonium hexafluorotitanate. The porous structure, surface property and state of TiO
[...] Read more.
Hydrophobic Y-zeolite (SiO2/Al2O3 = 810) and TiO2 composite photocatalysts were designed by using two different types of TiO2 precursors, i.e., titanium ammonium oxalate and ammonium hexafluorotitanate. The porous structure, surface property and state of TiO2 were investigated by various characterization techniques. By using an ammonium hexafluorotitanate as a precursor, hydrophobic modification of the Y-zeolite surface and realizing visible light sensitivity was successfully achieved at the same time after calcination at 773 K in the air. The prepared sample still maintained the porous structure of Y-zeolite and a large surface area. Highly crystalline anatase TiO2 was also formed on the Y-zeolite surface by the role of fluorine in the precursor. The usages of ammonium hexafluorotitanate were effective for the improvement of the photocatalytic performance of the composite in the degradation of 2-propanol in the gas phase under UV and visible light (λ > 420 nm) irradiation. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessArticle The Anthraquinone Derivatives from the Fungus Alternaria sp. XZSBG-1 from the Saline Lake in Bange, Tibet, China
Molecules 2014, 19(10), 16529-16542; doi:10.3390/molecules191016529
Received: 7 August 2014 / Revised: 17 September 2014 / Accepted: 19 September 2014 / Published: 14 October 2014
Cited by 4 | PDF Full-text (1023 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four new anthraquinone derivatives 14 were obtained along with seven known compounds 511 from the extracts of the fungal strain Alternaria sp. XZSBG-1 which was isolated from the sediments of the carbonate saline lake in Bange, Tibet, China.
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Four new anthraquinone derivatives 14 were obtained along with seven known compounds 511 from the extracts of the fungal strain Alternaria sp. XZSBG-1 which was isolated from the sediments of the carbonate saline lake in Bange, Tibet, China. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectra. Compound 1 is a novel tetrahydroanthraquinone with an epoxy ether bond between C-4a and C-9a. In the primary bioassays, compound 3 (alterporriol T) exhibited inhibition of a-glucosidase with a IC50 value 7.2 μM, and compound 9 showed good inhibitory activity against the HCT-116 and HeLa cell lines, with IC50 values of 3.03 and 8.09 μM, respectively. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Playing with Opening and Closing of Heterocycles: Using the Cusmano-Ruccia Reaction to Develop a Novel Class of Oxadiazolothiazinones, Active as Calcium Channel Modulators and P-Glycoprotein Inhibitors
Molecules 2014, 19(10), 16543-16572; doi:10.3390/molecules191016543
Received: 20 June 2014 / Revised: 15 August 2014 / Accepted: 4 September 2014 / Published: 14 October 2014
Cited by 3 | PDF Full-text (4448 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As a result of the ring-into-ring conversion of nitrosoimidazole derivatives, we obtained a molecular scaffold that, when properly decorated, is able to decrease inotropy by blocking L-type calcium channels. Previously, we used this scaffold to develop a quantitative structure-activity relationship (QSAR) model, and
[...] Read more.
As a result of the ring-into-ring conversion of nitrosoimidazole derivatives, we obtained a molecular scaffold that, when properly decorated, is able to decrease inotropy by blocking L-type calcium channels. Previously, we used this scaffold to develop a quantitative structure-activity relationship (QSAR) model, and we used the most potent oxadiazolothiazinone as a template for ligand-based virtual screening. Here, we enlarge the diversity of chemical decorations, present the synthesis and in vitro data for 11 new derivatives, and develop a new 3D-QSAR model with recent in silico techniques. We observed a key role played by the oxadiazolone moiety: given the presence of positively charged calcium ions in the transmembrane channel protein, we hypothesize the formation of a ternary complex between the oxadiazolothiazinone, the Ca2+ ion and the protein. We have supported this hypothesis by means of pharmacophore generation and through the docking of the pharmacophore into a homology model of the protein. We also studied with docking experiments the interaction with a homology model of P-glycoprotein, which is inhibited by this series of molecules, and provided further evidence toward the relevance of this scaffold in biological interactions. Full article
(This article belongs to the Special Issue In-Silico Drug Design and In-Silico Screening)
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Open AccessArticle Effects of Croton rhamnifolioides Essential Oil on Aedes aegypti Oviposition, Larval Toxicity and Trypsin Activity
Molecules 2014, 19(10), 16573-16587; doi:10.3390/molecules191016573
Received: 17 July 2014 / Revised: 15 September 2014 / Accepted: 26 September 2014 / Published: 14 October 2014
Cited by 10 | PDF Full-text (294 KB) | HTML Full-text | XML Full-text
Abstract
Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its
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Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its effects on oviposition and survival of larvae of the dengue fever mosquito Aedes aegypti. In addition, we have established a possible mechanism of action for the larvicidal activity of the essential oil. GC-MS analyses revealed marked differences in the composition of oil that had been freshly isolated and that of a sample that had been stored in a sealed amber-glass vial under refrigeration for three years. However, both fresh and stored oil exhibited substantial larvicidal activities with LC50 values of 122.35 and 89.03 ppm, respectively, and oviposition deterrent effects against gravid females at concentrations of 50 and 100 µg·mL−1. These results demonstrate that the larvicidal effect of the essential oil was unchanged during three years of storage even though its chemical composition altered. Hence, the essential oil could be used in the preparation of commercial products. In addition, we observed that the trypsin-like activity of mosquito larvae was inhibited in vitro by the essential oil of C. rhamnifolioides, suggesting that the larvicidal effect may be associated with inhibition of this enzyme. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro
Molecules 2014, 19(10), 16588-16608; doi:10.3390/molecules191016588
Received: 15 August 2014 / Revised: 16 September 2014 / Accepted: 23 September 2014 / Published: 15 October 2014
Cited by 22 | PDF Full-text (1648 KB) | HTML Full-text | XML Full-text
Abstract
Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects,
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Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects, including antiproliferative and anticarcinogenic activities, in several cancers. In the present study, we determined if deguelin would inhibit migration and invasion in U-2 OS human osteosarcoma cells. Deguelin significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells which was associated with a reduction of activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). Furthermore, results from western blotting indicated that deguelin decreased the cell proliferation and cell growth-associated protein levels, such as SOS1, PKC, Ras, PI3K, p-AKT(Ser473), IRE-1α, MEKK3, iNOS, COX2, p-ERK1/2, p-JNK1/2, p-p38; the cell motility and focal adhesion-associated protein levels, such as Rho A, FAK, ROCK-1; the invasion-associated protein levels, such as TIMP1, uPA, MMP-2. MMP-9, MMP-13, MMP-1 and VEGF in U-2 OS cells. Confocal microscopy revealed that deguelin reduced NF-κB p65, Rho A and ROCK-1 protein levels in cytosol. MMP-7, MMP-9 and Rho A mRNA levels were suppressed by deguelin. These in vitro results provide evidence that deguelin may have potential as a novel anti-cancer agent for the treatment of osteosarcoma and provides the rationale for in vivo studies in animal models. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Anti-Inflammatory Potential of Newly Synthesized 4-[(Butylsulfinyl)methyl]-1,2-benzenediol in Lipopolysaccharide-Stimulated BV2 Microglia
Molecules 2014, 19(10), 16609-16623; doi:10.3390/molecules191016609
Received: 28 July 2014 / Revised: 4 October 2014 / Accepted: 8 October 2014 / Published: 15 October 2014
Cited by 3 | PDF Full-text (1030 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we investigated the anti-inflammatory effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) in lipopolysaccharide (LPS)-stimulated BV2 microglia and the subsequent signaling events. Following stimulation with LPS, elevated production of nitric oxide (NO) and prostaglandin E2 (PGE2) was detected in
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In this study, we investigated the anti-inflammatory effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) in lipopolysaccharide (LPS)-stimulated BV2 microglia and the subsequent signaling events. Following stimulation with LPS, elevated production of nitric oxide (NO) and prostaglandin E2 (PGE2) was detected in BV2 cells; however, SMBD pretreatment inhibited the production of NO and PGE2 through suppressing gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, at non-toxic concentrations. LPS-stimulated gene expression and production of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were also significantly reduced by SMBD. The anti-inflammatory effects of SMBD were associated with suppression of LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), and phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a phosphatidylinositol 3-kinase (PI3K) downstream effector. Therefore, the present results demonstrate that SMBD down-regulates inflammatory gene expression by inhibiting the activation of NF-κB through interference with the activation of MAPKs and PI3K/Akt signaling. Taken together, our data suggest that SMBD may have potential to be developed into an effective anti-inflammatory agent. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Photocatalytic Solar Tower Reactor for the Elimination of a Low Concentration of VOCs
Molecules 2014, 19(10), 16624-16639; doi:10.3390/molecules191016624
Received: 28 August 2014 / Revised: 29 September 2014 / Accepted: 8 October 2014 / Published: 15 October 2014
Cited by 1 | PDF Full-text (3030 KB) | HTML Full-text | XML Full-text
Abstract
We developed a photocatalytic solar tower reactor for the elimination of low concentrations of volatile organic compounds (VOCs) typically emitted from small industrial establishments. The photocatalytic system can be installed in a narrow space, as the reactor is cylindrical-shaped. The photocatalytic reactor was
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We developed a photocatalytic solar tower reactor for the elimination of low concentrations of volatile organic compounds (VOCs) typically emitted from small industrial establishments. The photocatalytic system can be installed in a narrow space, as the reactor is cylindrical-shaped. The photocatalytic reactor was placed vertically in the center of a cylindrical scattering mirror, and this vertical reactor was irradiated with scattered sunlight generated by the scattering mirror. About 5 ppm toluene vapor, used as representative VOC, was continuously photodegraded and converted to CO2 almost stoichiometrically under sunny conditions. Toluene removal depended only on the intensity of sunlight. The performance of the solar tower reactor did not decrease with half a year of operation, and the average toluene removal was 36% within this period. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
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Open AccessArticle Influence of Sulfur Fumigation on the Chemical Constituents and Antioxidant Activity of Buds of Lonicera japonica
Molecules 2014, 19(10), 16640-16655; doi:10.3390/molecules191016640
Received: 6 September 2014 / Revised: 7 October 2014 / Accepted: 9 October 2014 / Published: 15 October 2014
Cited by 9 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lonicera japonica flos is widely used as a pharmaceutical resource and a commonly-employed ingredient in healthy food, soft beverages and cosmetics in China. Sometimes, sulfur fumigation is used during post-harvest handling. In this study, a comprehensive comparison of the chemical profile between sun-dried
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Lonicera japonica flos is widely used as a pharmaceutical resource and a commonly-employed ingredient in healthy food, soft beverages and cosmetics in China. Sometimes, sulfur fumigation is used during post-harvest handling. In this study, a comprehensive comparison of the chemical profile between sun-dried and sulfur-fumigated samples was conducted by HPLC fingerprints and simultaneous quantification of nine constituents, including secologanic acid, along with another eight usually-analyzed markers. Secologanic acid was destroyed, and its sulfonates were generated, whereas caffeoylquinic acids were protected from being oxidized. The residual sulfur dioxide in sulfur-fumigated samples was significantly higher than that in sun-dried samples, which might increase the potential incidence of toxicity to humans. Meanwhile, compared with sun-dried samples, sulfur-fumigated samples have significantly stronger antioxidant activity, which could be attributed to the joint effect of protected phenolic acids and flavonoids, as well as newly-generated iridoid sulfonates. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Anti-Obesity Effects of Hispidin and Alpinia zerumbet Bioactives in 3T3-L1 Adipocytes
Molecules 2014, 19(10), 16656-16671; doi:10.3390/molecules191016656
Received: 31 August 2014 / Revised: 22 September 2014 / Accepted: 10 October 2014 / Published: 15 October 2014
Cited by 8 | PDF Full-text (574 KB) | HTML Full-text | XML Full-text
Abstract
Obesity and its related disorders have become leading metabolic diseases. In the present study, we used 3T3-L1 adipocytes to investigate the anti-obesity activity of hispidin and two related compounds that were isolated from Alpinia zerumbet (alpinia) rhizomes. The results showed that hispidin, dihydro-5,6-dehydrokawain
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Obesity and its related disorders have become leading metabolic diseases. In the present study, we used 3T3-L1 adipocytes to investigate the anti-obesity activity of hispidin and two related compounds that were isolated from Alpinia zerumbet (alpinia) rhizomes. The results showed that hispidin, dihydro-5,6-dehydrokawain (DDK), and 5,6-dehydrokawain (DK) have promising anti-obesity properties. In particular, all three compounds significantly increased intracellular cyclic adenosine monophosphate (cAMP) concentrations by 81.2% ± 0.06%, 67.0% ± 1.62%, and 56.9% ± 0.19%, respectively. Hispidin also stimulated glycerol release by 276.4% ± 0.8% and inhibited lipid accumulation by 47.8% ± 0.16%. Hispidin and DDK decreased intracellular triglyceride content by 79.5% ± 1.37% and 70.2% ± 1.4%, respectively, and all three compounds inhibited glycerol-3-phosphate dehydrogenase (GPDH) and pancreatic lipase, with hispidin and DDK being the most potent inhibitors. Finally, none of the three compounds reduced 3T3-L1 adipocyte viability. These results highlight the potential for developing hispidin and its derivatives as anti-obesity compounds. Full article
(This article belongs to the Special Issue Prodrugs)
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Open AccessArticle Optimization of Natural Lipstick Formulation Based on Pitaya (Hylocereus polyrhizus) Seed Oil Using D-Optimal Mixture Experimental Design
Molecules 2014, 19(10), 16672-16683; doi:10.3390/molecules191016672
Received: 11 August 2014 / Revised: 25 September 2014 / Accepted: 26 September 2014 / Published: 16 October 2014
Cited by 9 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text
Abstract
The D-optimal mixture experimental design was employed to optimize the melting point of natural lipstick based on pitaya (Hylocereus polyrhizus) seed oil. The influence of the main lipstick components—pitaya seed oil (10%–25% w/w), virgin coconut oil (25%–45% w/w), beeswax (5%–25% w/w),
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The D-optimal mixture experimental design was employed to optimize the melting point of natural lipstick based on pitaya (Hylocereus polyrhizus) seed oil. The influence of the main lipstick components—pitaya seed oil (10%–25% w/w), virgin coconut oil (25%–45% w/w), beeswax (5%–25% w/w), candelilla wax (1%–5% w/w) and carnauba wax (1%–5% w/w)—were investigated with respect to the melting point properties of the lipstick formulation. The D-optimal mixture experimental design was applied to optimize the properties of lipstick by focusing on the melting point with respect to the above influencing components. The D-optimal mixture design analysis showed that the variation in the response (melting point) could be depicted as a quadratic function of the main components of the lipstick. The best combination of each significant factor determined by the D-optimal mixture design was established to be pitaya seed oil (25% w/w), virgin coconut oil (37% w/w), beeswax (17% w/w), candelilla wax (2% w/w) and carnauba wax (2% w/w). With respect to these factors, the 46.0 °C melting point property was observed experimentally, similar to the theoretical prediction of 46.5 °C. Carnauba wax is the most influential factor on this response (melting point) with its function being with respect to heat endurance. The quadratic polynomial model sufficiently fit the experimental data. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Production of Anti-Cancer Agent Using Microbial Biotransformation
Molecules 2014, 19(10), 16684-16692; doi:10.3390/molecules191016684
Received: 4 September 2014 / Revised: 10 October 2014 / Accepted: 11 October 2014 / Published: 16 October 2014
Cited by 1 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text
Abstract
Microbial biotransformation is a great model system to produce drugs and biologically active compounds. In this study, we elucidated the fermentation and production of an anti-cancer agent from a microbial process for regiospecific hydroxylation of resveratrol. Among the strains examined, a potent strain
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Microbial biotransformation is a great model system to produce drugs and biologically active compounds. In this study, we elucidated the fermentation and production of an anti-cancer agent from a microbial process for regiospecific hydroxylation of resveratrol. Among the strains examined, a potent strain showed high regiospecific hydroxylation activity to produce piceatannol. In a 5 L (w/v 3 L) jar fermentation, this wild type Streptomyces sp. in the batch system produced 205 mg of piceatannol (i.e., 60% yields) from 342 mg of resveratrol in 20 h. Using the product, an in vitro anti-cancer study was performed against a human cancer cell line (HeLa). It showed that the biotransformed piceatannol possessed a significant anticancer activity. This result demonstrates that a biotransformation screening method might be of therapeutic interest with respect to the identification of anti-cancer drugs. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Changes in Nutritional Metabolites of Young Ginger (Zingiber officinale Roscoe) in Response to Elevated Carbon Dioxide
Molecules 2014, 19(10), 16693-16706; doi:10.3390/molecules191016693
Received: 8 July 2014 / Revised: 23 September 2014 / Accepted: 23 September 2014 / Published: 16 October 2014
PDF Full-text (243 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The increase of atmospheric CO2 due to global climate change or horticultural practices has direct and indirect effects on food crop quality. One question that needs to be asked, is whether CO2 enrichment affects the nutritional quality of Malaysian young ginger
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The increase of atmospheric CO2 due to global climate change or horticultural practices has direct and indirect effects on food crop quality. One question that needs to be asked, is whether CO2 enrichment affects the nutritional quality of Malaysian young ginger plants. Responses of total carbohydrate, fructose, glucose, sucrose, protein, soluble amino acids and antinutrients to either ambient (400 μmol/mol) and elevated (800 μmol/mol) CO2 treatments were determined in the leaf and rhizome of two ginger varieties namely Halia Bentong and Halia Bara. Increasing of CO2 level from ambient to elevated resulted in increased content of total carbohydrate, sucrose, glucose, and fructose in the leaf and rhizome of ginger varieties. Sucrose was the major sugar followed by glucose and fructose in the leaf and rhizome extract of both varieties. Elevated CO2 resulted in a reduction of total protein content in the leaf (H. Bentong: 38.0%; H. Bara: 35.4%) and rhizome (H. Bentong: 29.0%; H. Bara: 46.2%). In addition, under CO2 enrichment, the concentration of amino acids increased by approximately 14.5% and 98.9% in H. Bentong and 12.0% and 110.3% in H. Bara leaf and rhizome, respectively. The antinutrient contents (cyanide and tannin) except phytic acid were influenced significantly (P ≤ 0.05) by CO2 concentration. Leaf extract of H. Bara exposed to elevated CO2 exhibited highest content of cyanide (336.1 mg HCN/kg DW), while, highest content of tannin (27.5 g/kg DW) and phytic acid (54.1 g/kg DW) were recorded from H.Bara rhizome grown under elevated CO2. These results demonstrate that the CO2 enrichment technique could improve content of some amino acids and antinutrients of ginger as a food crop by enhancing its nutritional and health-promoting properties. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans
Molecules 2014, 19(10), 16707-16723; doi:10.3390/molecules191016707
Received: 10 July 2014 / Revised: 22 August 2014 / Accepted: 15 September 2014 / Published: 16 October 2014
Cited by 5 | PDF Full-text (1012 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number
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Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa). A subset of monosubstituted 5-aryl-2-aminoimidazoles showed a moderate safety window, with therapeutic indices (TIs) ranging between 3 and 20. Whereas introduction of a (cyclo-)alkyl chain at the N1-position strongly reduced the TI, introduction of a (cyclo-)alkyl chain or a triazole moiety at the 2N-position increased the TI up to 370. Since a promising application of preventive anti-biofilm agents is their use in anti-biofilm coatings for orthopedic implants, their effects on cell viability and functional behavior of human osteoblasts and bone marrow derived mesenchymal stem cells were tested. The 2N-substituted 5-aryl-2-aminoimidazoles consistently showed the lowest toxicity and allowed survival of the bone cells for up to 4 weeks. Moreover they did not negatively affect the osteogenic differentiation potential of the bone cells. Finally, we examined the effect of the compounds on the survival of Caenorhabditis elegans, which confirmed the higher safety window of 2N-substituted 5-aryl-2-aminoimidazoles. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Impact of Trans-Resveratrol-Sulfates and -Glucuronides on Endothelial Nitric Oxide Synthase Activity, Nitric Oxide Release and Intracellular Reactive Oxygen Species
Molecules 2014, 19(10), 16724-16736; doi:10.3390/molecules191016724
Received: 29 August 2014 / Revised: 30 September 2014 / Accepted: 13 October 2014 / Published: 17 October 2014
Cited by 13 | PDF Full-text (920 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen
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Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings. Full article
(This article belongs to the Special Issue Resveratrol)
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Open AccessArticle Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines
Molecules 2014, 19(10), 16737-16756; doi:10.3390/molecules191016737
Received: 31 July 2014 / Revised: 26 September 2014 / Accepted: 13 October 2014 / Published: 17 October 2014
Cited by 7 | PDF Full-text (378 KB) | HTML Full-text | XML Full-text
Abstract
The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of
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The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics. Full article
(This article belongs to the Special Issue Cycloaddition Chemistry)
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Open AccessArticle Pharmacokinetic Comparisons of Benzoylmesaconine in Rats Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry after Administration of Pure Benzoylmesaconine and Wutou Decoction
Molecules 2014, 19(10), 16757-16769; doi:10.3390/molecules191016757
Received: 11 September 2014 / Revised: 8 October 2014 / Accepted: 8 October 2014 / Published: 17 October 2014
Cited by 5 | PDF Full-text (662 KB) | HTML Full-text | XML Full-text
Abstract
Wutou decoction is widely used in China because of its therapeutic effect on rheumatoid arthritis. Benzoylmesaconine (BMA), the most abundant component of Wutou decoction, was used as the marker compound for the pharmacokinetic study of Wutou decoction. The aim of the present study
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Wutou decoction is widely used in China because of its therapeutic effect on rheumatoid arthritis. Benzoylmesaconine (BMA), the most abundant component of Wutou decoction, was used as the marker compound for the pharmacokinetic study of Wutou decoction. The aim of the present study was to compare the pharmacokinetics of BMA in rats after oral administration of pure BMA and Wutou decoction. Pure BMA (5 mg/kg) and Wutou decoction (0.54 g/kg, equivalent to 5 mg/kg BMA) were orally administered to rats with blood samples collected over 10 h. Quantification of BMA in rat plasma was achieved using sensitive and validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Specifically, the half-life (T1/2) and mean residence time values of pure BMA were 228.3 ± 117.0 min and 155.0 ± 33.2 min, respectively, whereas those of BMA in Wutou decoction were decreased to 61.8 ± 35.1 min and 55.8 ± 16.4 min, respectively. The area under the curve (AUC) of BMA after administration of Wutou decoction was significantly decreased (five-fold) compared with that of pure BMA. The results indicate that the elimination of BMA in rats after the administration of Wutou decoction was significantly faster compared with that of pure BMA. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A New Urease Inhibitor from Viola betonicifolia
Molecules 2014, 19(10), 16770-16778; doi:10.3390/molecules191016770
Received: 13 August 2014 / Revised: 24 September 2014 / Accepted: 25 September 2014 / Published: 17 October 2014
Cited by 7 | PDF Full-text (589 KB) | HTML Full-text | XML Full-text
Abstract
Urease has attracted much attention, as it is directly involved in the formation of infection stones and contributes to the pathogenesis of urolithiasis, pyelonephritis, ammonia and hepatic encephalopathy, hepatic coma and urinary catheter encrustation. Moreover, urease is the major cause of pathologies induced
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Urease has attracted much attention, as it is directly involved in the formation of infection stones and contributes to the pathogenesis of urolithiasis, pyelonephritis, ammonia and hepatic encephalopathy, hepatic coma and urinary catheter encrustation. Moreover, urease is the major cause of pathologies induced by H. pylori, such as gastritis and peptic ulcer. In the present work, the new natural compound, 3-methoxydalbergione, was isolated from Viola betonicifolia. A mechanistic study of this compound as a natural urease inhibitor was performed by using enzyme kinetics and docking studies. 3-Methoxydalbergione could be considered as a lead molecule for drugs useful in the urease associated diseases. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Biomimetic Adhesive Materials Containing Cyanoacryl Group for Medical Application
Molecules 2014, 19(10), 16779-16793; doi:10.3390/molecules191016779
Received: 17 August 2014 / Revised: 19 September 2014 / Accepted: 25 September 2014 / Published: 17 October 2014
Cited by 3 | PDF Full-text (1642 KB) | HTML Full-text | XML Full-text
Abstract
For underwater adhesives with biocompatible and more flexible bonds using biomimetic adhesive groups, DOPA-like adhesive molecules were modified with cyanoacrylates to obtain different repeating units and chain length copolymers. The goal of this work is to copy the mechanisms of underwater bonding to
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For underwater adhesives with biocompatible and more flexible bonds using biomimetic adhesive groups, DOPA-like adhesive molecules were modified with cyanoacrylates to obtain different repeating units and chain length copolymers. The goal of this work is to copy the mechanisms of underwater bonding to create synthetic water-borne underwater medical adhesives through blending of the modified DOPA and a triblock copolymer (PEO-PPO-PEO) for practical application to repair wet living tissues and bones, and in turn, to use the synthetic adhesives to test mechanistic hypotheses about the natural adhesive. The highest values in stress and modulus of the biomimetic adhesives prepared in wet state were 165 kPa and 33 MPa, respectively. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Substrate Specificity and Enzyme Recycling Using Chitosan Immobilized Laccase
Molecules 2014, 19(10), 16794-16809; doi:10.3390/molecules191016794
Received: 16 May 2014 / Revised: 22 September 2014 / Accepted: 8 October 2014 / Published: 17 October 2014
Cited by 9 | PDF Full-text (389 KB) | HTML Full-text | XML Full-text
Abstract
The immobilization of laccase (Aspergillus sp.) on chitosan by cross-linking and its application in bioconversion of phenolic compounds in batch reactors were studied. Investigation was performed using laccase immobilized via chemical cross-linking due to the higher enzymatic operational stability of this method
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The immobilization of laccase (Aspergillus sp.) on chitosan by cross-linking and its application in bioconversion of phenolic compounds in batch reactors were studied. Investigation was performed using laccase immobilized via chemical cross-linking due to the higher enzymatic operational stability of this method as compared to immobilization via physical adsorption. To assess the influence of different substrate functional groups on the enzyme’s catalytic efficiency, substrate specificity was investigated using chitosan-immobilized laccase and eighteen different phenol derivatives. It was observed that 4-nitrophenol was not oxidized, while 2,5-xylenol, 2,6-xylenol, 2,3,5-trimethylphenol, syringaldazine, 2,6-dimetoxyphenol and ethylphenol showed reaction yields up 90% at 40 °C. The kinetic of process, enzyme recyclability and operational stability were studied. In batch reactors, it was not possible to reuse the enzyme when it was applied to syringaldazne bioconversion. However, when the enzyme was applied to bioconversion of 2,6-DMP, the activity was stable for eight reaction batches. Full article
(This article belongs to the Special Issue Enzyme Immobilization)
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Open AccessArticle Physicochemical and Antioxidant Properties of Black Garlic
Molecules 2014, 19(10), 16811-16823; doi:10.3390/molecules191016811
Received: 11 August 2014 / Revised: 22 September 2014 / Accepted: 29 September 2014 / Published: 20 October 2014
Cited by 12 | PDF Full-text (547 KB) | HTML Full-text | XML Full-text
Abstract
Black garlic (BG) is a processed garlic product prepared by heat treatment of whole garlic bulbs (Allium sativum L.) at high temperature under high humidity for several days, resulting in black cloves with a sweet taste. BG has recently been introduced to
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Black garlic (BG) is a processed garlic product prepared by heat treatment of whole garlic bulbs (Allium sativum L.) at high temperature under high humidity for several days, resulting in black cloves with a sweet taste. BG has recently been introduced to the Korean market as a product beneficial to health. To clarify how BG changes during the 35 day aging period, the physicochemical characteristics, antioxidant contents, and antioxidant activities were evaluated under controlled conditions of 70 °C and 90% relative humidity. Reducing sugar and total acidity of BG increased during the aging period, whereas pH decreased from pH 6.33 to 3.74. Lightness and yellowness values of BG radically decreased during the aging period, whereas redness values increased significantly. Antioxidant components, including the total polyphenol and total flavonoids contents of BG, increased significantly until the 21st day of aging (p < 0.05) and correspondingly, the antioxidant activities of BG, measured by DPPH, ABTS, FRAP, and reducing power assays, were highest on the 21st day of aging. These results indicate that BG can be considered to not only possess antioxidant properties during the aging period, but also to reach its optimal antioxidant properties at the 21st day of aging. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Quality Evaluation of Pharmaceutical Formulations Containing Hydrochlorothiazide
Molecules 2014, 19(10), 16824-16836; doi:10.3390/molecules191016824
Received: 23 July 2014 / Revised: 13 October 2014 / Accepted: 15 October 2014 / Published: 20 October 2014
Cited by 2 | PDF Full-text (338 KB) | HTML Full-text | XML Full-text
Abstract
Hydrochlorothiazide is a diuretic used to treat hypertension that belongs to class IV of the Biopharmaceutics Classification System. The drug was evaluated by quality control, thermal characterization tests, and pharmaceutical formulation compatibility studies. It was concluded that the generic drug, Lab 2, was
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Hydrochlorothiazide is a diuretic used to treat hypertension that belongs to class IV of the Biopharmaceutics Classification System. The drug was evaluated by quality control, thermal characterization tests, and pharmaceutical formulation compatibility studies. It was concluded that the generic drug, Lab 2, was not a pharmaceutical equivalent. The compounded drugs, Lab 5 and Lab 6, produced unsatisfactory but expected results, since there is no requirement for dissolution and dissolution profile testing for the commercialization of these products. In a compatibility study, lactose and mannitol were shown to be incompatible with HCTZ, which may explain the lack of equivalence of the generic pharmaceutical product, associated with other situations. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Effect of Tea Polyphenols on Lipid Peroxidation and Antioxidant Activity of Litchi (Litchi chinensis Sonn.) Fruit during Cold Storage
Molecules 2014, 19(10), 16837-16850; doi:10.3390/molecules191016837
Received: 23 August 2014 / Revised: 29 September 2014 / Accepted: 8 October 2014 / Published: 20 October 2014
Cited by 5 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
To understand the potential of application of tea polyphenols to the shelf life extension and quality maintenance of litchi (Litchi chinensis Sonn.) fruit, the fruits were dipped into a solution of 1% tea phenols for 5 min before cold storage at 4
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To understand the potential of application of tea polyphenols to the shelf life extension and quality maintenance of litchi (Litchi chinensis Sonn.) fruit, the fruits were dipped into a solution of 1% tea phenols for 5 min before cold storage at 4 °C. Changes in browning index, contents of anthocyanins and phenolic compounds, superoxide dismutase (SOD) and peroxidase (POD) activities, O2.− production rate and H2O2 content, levels of relative leakage rate and lipid peroxidation, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were measured after 0, 10, 20 and 30 days of cold storage. The results showed that application of tea polyphenols markedly delayed pericarp browning, alleviated the decreases in contents of total soluble solids (TSS) and ascorbic acid, and maintained relatively high levels of total phenolics and anthocyanins of litchi fruit after 30 days of cold storage. Meanwhile, the treatment reduced the increases in relative leakage rate and lipid peroxidation content, delayed the increases in both O2.− production rate and H2O2 contents, and increased SOD activity but reduced POD activity throughout this storage period. These data indicated that the delayed pericarp browning of litchi fruit by the treatment with tea polyphenols could be due to enhanced antioxidant capability, reduced accumulations of reactive oxygen species and lipid peroxidation, and improved membrane integrity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle The Use of Headspace Solid-Phase Microextraction (HS-SPME) to Assess the Quality and Stability of Fruit Products: An Example Using Red Mombin Pulp (Spondias purpurea L.)
Molecules 2014, 19(10), 16851-16860; doi:10.3390/molecules191016851
Received: 10 April 2014 / Revised: 18 June 2014 / Accepted: 27 June 2014 / Published: 21 October 2014
Cited by 1 | PDF Full-text (560 KB) | HTML Full-text | XML Full-text
Abstract
The present study aimed to evaluate the volatiles profile of red mombin (Spondias purpurea) pulp and its powder produced by spray-drying (SD) as an example to show utility of headspace solid-phase microextraction (HS-SPME) in the analysis of parameters such as the
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The present study aimed to evaluate the volatiles profile of red mombin (Spondias purpurea) pulp and its powder produced by spray-drying (SD) as an example to show utility of headspace solid-phase microextraction (HS-SPME) in the analysis of parameters such as the quality and stability of fruit products. Volatiles profiles of the pulp were identified by gas chromatography-mass spectrometry (GC-MS), quantified by gas chromatography-flame ionization detector (GC-FID) and compared to the profile of the powder stored at 0, 60 and 120 days in plastic (PP) or laminated packages (LP). The results showed that the technique was able to identify 36 compounds in the red mombin pulp, 17 out of which have been described for the first time in this fruit, showing that red mombin fresh pulp appears to be unique in terms of volatiles composition. However, only 24 compounds were detected in the powder. This decrease is highly correlated (r2 = 0.99), at least for the majority of compounds, to the degree of volatility of compounds. Furthermore, the powder stored in PP or LP showed no statistical differences in the amounts of its components for a period of 120 days of storage. Finally, this work shows how HS-SPME analysis can be a valuable tool to assess the quality and stability of fruit products. Full article
(This article belongs to the Special Issue Microextraction)
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Open AccessArticle Ionization States, Cellular Toxicity and Molecular Modeling Studies of Midazolam Complexed with Trimethyl-β-Cyclodextrin
Molecules 2014, 19(10), 16861-16876; doi:10.3390/molecules191016861
Received: 10 September 2014 / Revised: 6 October 2014 / Accepted: 15 October 2014 / Published: 21 October 2014
Cited by 5 | PDF Full-text (783 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We investigated the ionization profiles for open-ring (OR) and closed-ring (CR) forms of midazolam and drug-binding modes with heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (trimethyl-β-cyclodextrin; TRIMEB) using molecular modeling techniques and quantum mechanics methods. The results indicated that the total net charges for different molecular forms of midazolam
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We investigated the ionization profiles for open-ring (OR) and closed-ring (CR) forms of midazolam and drug-binding modes with heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (trimethyl-β-cyclodextrin; TRIMEB) using molecular modeling techniques and quantum mechanics methods. The results indicated that the total net charges for different molecular forms of midazolam tend to be cationic for OR and neutral for CR at physiological pH levels. The thermodynamic calculations demonstrated that CR is less water-soluble than OR, mainly due to the maximal solvation energy (\(\Delta G_{solv}^{CR}\) = −9.98 kcal·mol\(^{−1}\)), which has a minimal \(\Delta G_{solv}^{OR}\) of −67.01 kcal·mol\(^{−1}\). A cell viability assay did not detect any signs of TRIMEB and OR/CR-TRIMEB complex toxicity on the cEND cells after 24 h of incubation in either Dulbecco's Modified Eagles Medium or in heat-inactivated human serum. The molecular docking studies identified the more flexible OR form of midazolam as being a better binder to TRIMEB with the fluorophenyl ring introduced inside the amphiphilic cavity of the host molecule. The OR binding affinity was confirmed by a minimal Gibbs free energy of binding (\(\Delta G_{bind}\)) value of −5.57 ± 0.02 kcal·mol\(^{−1}\), an equilibrium binding constant (\(K_{b}\)) of 79.89 ± 2.706 μM, and a ligand efficiency index (\(LE_{lig}\)) of −0.21 ± 0.001. Our current data suggest that in order to improve the clinical applications of midazolam via its complexation with trimethyl-β-cyclodextrin to increase drug's overall aqueous solubility, it is important to concern the different forms and ionization states of this anesthetic. All mean values are indicated with their standard deviations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Radiation-Induced High-Temperature Conversion of Cellulose
Molecules 2014, 19(10), 16877-16908; doi:10.3390/molecules191016877
Received: 9 September 2014 / Revised: 22 September 2014 / Accepted: 28 September 2014 / Published: 21 October 2014
Cited by 3 | PDF Full-text (906 KB) | HTML Full-text | XML Full-text
Abstract
Thermal decomposition of cellulose can be upgraded by means of an electron-beam irradiation to produce valuable organic products via chain mechanisms. The samples being irradiated decompose effectively at temperatures below the threshold of pyrolysis inception. Cellulose decomposition resembles local “explosion” of the glucopyranose
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Thermal decomposition of cellulose can be upgraded by means of an electron-beam irradiation to produce valuable organic products via chain mechanisms. The samples being irradiated decompose effectively at temperatures below the threshold of pyrolysis inception. Cellulose decomposition resembles local “explosion” of the glucopyranose unit when fast elimination of carbon dioxide and water precede formation of residual carbonyl or carboxyl compounds. The dry distillation being performed during an irradiation gives a liquid condensate where furfural and its derivatives are dominant components. Excessively fast heating is adverse, as it results in a decrease of the yield of key organic products because pyrolysis predominates over the radiolytic-controlled decomposition of feedstock. Most likely, conversion of cellulose starts via radiolytic formation of macroradicals do not conform with each other, resulting in instability of the macroradical. As a consequence, glucosidic bond cleavage, elimination of light fragments (water, carbon oxides, formaldehyde, etc.) and formation of furfural take place. Full article
(This article belongs to the Special Issue New Trends in Cellulose and Chitin Chemistry)
Open AccessArticle Effects of Yerba maté, a Plant Extract Formulation (“YGD”) and Resveratrol in 3T3-L1 Adipogenesis
Molecules 2014, 19(10), 16909-16924; doi:10.3390/molecules191016909
Received: 27 June 2014 / Revised: 24 September 2014 / Accepted: 9 October 2014 / Published: 21 October 2014
Cited by 7 | PDF Full-text (846 KB) | HTML Full-text | XML Full-text
Abstract
We aimed to evaluate the in vitro effects of yerba maté, YGD (a herbal preparation containing yerba maté, guarana and damiana), and resveratrol on adipogenesis. The anti-adipogenic effects of yerba mate, YGD, resveratrol and YGD + resveratrol and yerba mate
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We aimed to evaluate the in vitro effects of yerba maté, YGD (a herbal preparation containing yerba maté, guarana and damiana), and resveratrol on adipogenesis. The anti-adipogenic effects of yerba mate, YGD, resveratrol and YGD + resveratrol and yerba mate + resveratrol combinations were evaluated in 3T3-L1 cells by Oil Red staining, cellular triglyceride content, and PCR quantitative array. The results demonstrated that all of the tested compounds inhibited adipogenesis. Yerba maté extract significantly down-regulated the expression of genes that play an important role in regulating adipogenesis, such as Adig, Axin, Cebpa, Fgf10, Lep, Lpl, and Pparγ2. In addition, these genes, YGD also repressed Bmp2, Ccnd1, Fasn, and Srebf1. Resveratrol also modulated the expression of Adig, Bmp2, Ccnd1, C/EBPα, Fasn, Fgf10, Lep, Lpl, and Pparγ2. Moreover, resveratrol repressed Cebpb, Cdk4, Fgf2, and Klf15. The yerba maté extract and YGD up-regulated the expression of genes involved in inhibiting adipogenesis, such as Dlk-1, Klf2, and Ucp1. Resveratrol also induced the expression of Klf2 and Ucp1. In addition resveratrol modulated the Ddit3, Foxo1, Sirt1, and Sirt2. The combined effects of these compounds on gene expression showed similar results observed from individual treatments. Our data indicates that the synergy between the compounds favors the inhibition of adipogenesis. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Effects of Ginsenoside Rg1 on the Expression of Toll-Like Receptor 3, 4 and Their Signalling Transduction Factors in the NG108-15 Murine Neuroglial Cell Line
Molecules 2014, 19(10), 16925-16936; doi:10.3390/molecules191016925
Received: 10 August 2014 / Revised: 7 October 2014 / Accepted: 8 October 2014 / Published: 22 October 2014
Cited by 9 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text
Abstract
As one of the most important components of Panax ginseng, ginsenoside Rg1 has certain anti-aging effects, improving the activity of learning and memory. Studies have showed that ginsenoside Rg1 improves the memory impairment associated with Alzheimer’s disease (AD). In this study, the
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As one of the most important components of Panax ginseng, ginsenoside Rg1 has certain anti-aging effects, improving the activity of learning and memory. Studies have showed that ginsenoside Rg1 improves the memory impairment associated with Alzheimer’s disease (AD). In this study, the effects of ginsenoside Rg1 were investigated through the activity of toll-like receptor (TLR) 3, TLR4 and their signaling transduction pathways in amyloid β peptide 25–35 (Aβ25–35) induced AD cell model. Thus we investigated several critical components of the TLR pathway. The neuroglial cell line NG108-15 was stimulated with or without Aβ25–35, while different concentrations of ginsenoside Rg1 were administered. After 24 h, tumor necrosis factor-α (TNF-α), interferon-β (IFN-β) in cell supernatant and inducible nitric oxide synthase (iNOS) in cell lysate supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). The mRNA and protein expression of TLR3, TLR4, nuclear factor kappa B (NF-κB) and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were detected by real-time PCR and western blot methods, respectively. The experimental results showed that Aβ25–35 could markedly raise the level of TNF-α, IFN-β and iNOS, and increase the expressions of mRNA and TLR3, TLR4, NF-κB and TRAF-6 protein in the NG108-15 cells. At the same time, the ginsenoside Rg1 significantly reduced the expressions of proteins and mRNA of TLR3, TLR4, NF-κB and TRAF-6, and down-regulated the levels of TNF-α, IFN-β of cell supernatant and iNOS of cell lysate supernatant in a concentration-dependent manner. In conclusion, ginsenoside Rg1 has good activity for suppressing the signaling transduction pathway of TLR3 and TLR4, and decreasing the inflammation factors induced by Aβ25–35 in NG108-15 cells, and this may be the mechanism of ginsenoside Rg1 action in AD treatment, but more studies are needed to identify its specificity. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Identification and Characterization of Amlexanox as a G Protein-Coupled Receptor Kinase 5 Inhibitor
Molecules 2014, 19(10), 16937-16949; doi:10.3390/molecules191016937
Received: 8 September 2014 / Revised: 11 October 2014 / Accepted: 14 October 2014 / Published: 22 October 2014
Cited by 12 | PDF Full-text (1098 KB) | HTML Full-text | XML Full-text
Abstract
G protein-coupled receptor kinases (GRKs) have been implicated in human diseases ranging from heart failure to diabetes. Previous studies have identified several compounds that selectively inhibit GRK2, such as paroxetine and balanol. Far fewer selective inhibitors have been reported for GRK5, a target
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G protein-coupled receptor kinases (GRKs) have been implicated in human diseases ranging from heart failure to diabetes. Previous studies have identified several compounds that selectively inhibit GRK2, such as paroxetine and balanol. Far fewer selective inhibitors have been reported for GRK5, a target for the treatment of cardiac hypertrophy, and the mechanism of action of reported compounds is unknown. To identify novel scaffolds that selectively inhibit GRK5, a differential scanning fluorometry screen was used to probe a library of 4480 compounds. The best hit was amlexanox, an FDA-approved anti-inflammatory, anti-allergic immunomodulator. The crystal structure of amlexanox in complex with GRK1 demonstrates that its tricyclic aromatic ring system forms ATP-like interactions with the hinge of the kinase domain, which is likely similar to how this drug binds to IκB kinase ε (IKKε), another kinase known to be inhibited by this compound. Amlexanox was also able to inhibit myocyte enhancer factor 2 transcriptional activity in neonatal rat ventricular myocytes in a manner consistent with GRK5 inhibition. The GRK1 amlexanox structure thus serves as a springboard for the rational design of inhibitors with improved potency and selectivity for GRK5 and IKKε. Full article
(This article belongs to the Special Issue Design and Study of Kinase Inhibitors)
Open AccessArticle Antioxidant, 5-Lipoxygenase Inhibitory and Cytotoxic Activities of Compounds Isolated from the Ferula lutea Flowers
Molecules 2014, 19(10), 16959-16975; doi:10.3390/molecules191016959
Received: 27 August 2014 / Revised: 11 October 2014 / Accepted: 15 October 2014 / Published: 22 October 2014
Cited by 18 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text
Abstract
A phytochemical investigation of the Ferula lutea (Poir.) Maire flowers has led to the isolation of a new compound, (E)-5-ethylidenefuran-2(5H)-one-5-O-β-D-glucopyranoside (1), designated ferunide, 4-hydroxy-3-methylbut-2-enoic acid (2), reported for the first time as a natural product,
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A phytochemical investigation of the Ferula lutea (Poir.) Maire flowers has led to the isolation of a new compound, (E)-5-ethylidenefuran-2(5H)-one-5-O-β-D-glucopyranoside (1), designated ferunide, 4-hydroxy-3-methylbut-2-enoic acid (2), reported for the first time as a natural product, together with nine known compounds, verbenone-5-O-β-D-glucopyranoside (3), 5-O-caffeoylquinic acid (4), methyl caffeate (5), methyl 3,5-O-dicaffeoylquinate (6), 3,5-O-dicaffeoylquinic acid (7), isorhamnetin-3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside, narcissin (8), (−)-marmesin (9), isoimperatorin (10) and 2,3,6-trimethylbenzaldehyde (11). Compounds 310 were identified for the first time in Ferula genus. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments, mass spectroscopy and X-ray diffraction analysis (compound 2), as well as by comparison with literature data. The antioxidant, anti-inflammatory and cytotoxic activities of isolated compounds were evaluated. Results showed that compound 7 exhibited the highest antioxidant activity with IC50 values of 18 ± 0.5 µmol/L and 19.7 ± 0.7 µmol/L by DPPH radical and ABTS radical cation, respectively. The compound 6 exhibited the highest anti-inflammatory activity with an IC50 value of 5.3 ± 0.1 µmol/L against 5-lipoxygenase. In addition, compound 5 was found to be the most cytotoxic, with IC50 values of 22.5 ± 2.4 µmol/L, 17.8 ± 1.1 µmol/L and 25 ± 1.1 µmol/L against the HCT-116, IGROV-1 and OVCAR-3 cell lines, respectively. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Formation of Mixed-Ligand Complexes of Pd2+ with Nucleoside 5'-Monophosphates and Some Metal-Ion-Binding Nucleoside Surrogates
Molecules 2014, 19(10), 16976-16986; doi:10.3390/molecules191016976
Received: 16 September 2014 / Revised: 8 October 2014 / Accepted: 17 October 2014 / Published: 22 October 2014
Cited by 6 | PDF Full-text (449 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Formation of mixed-ligand Pd2+ complexes between canonical nucleoside 5'-monophosphates and five metal-ion-binding nucleoside analogs has been studied by 1H-NMR spectroscopy to test the ability of these nucleoside surrogates to discriminate between unmodified nucleobases by Pd2+-mediated base pairing. The nucleoside
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Formation of mixed-ligand Pd2+ complexes between canonical nucleoside 5'-monophosphates and five metal-ion-binding nucleoside analogs has been studied by 1H-NMR spectroscopy to test the ability of these nucleoside surrogates to discriminate between unmodified nucleobases by Pd2+-mediated base pairing. The nucleoside analogs studied included 2,6-bis(3,5-dimethylpyrazol-1-yl)-, 2,6-bis(1-methylhydrazinyl)- and 6-(3,5-dimethylpyrazol-1-yl)-substituted 9-(β-d-ribofuranosyl)purines 13, and 2,4-bis(3,5-dimethylpyrazol-1-yl)- and 2,4-bis(1-methylhydrazinyl)-substituted 5-(β-d-ribofuranosyl)-pyrimidines 45. Among these, the purine derivatives 1-3 bound Pd2+ much more tightly than the pyrimidine derivatives 4, 5 despite apparently similar structures of the potential coordination sites. Compounds 1 and 2 formed markedly stable mixed-ligand Pd2+ complexes with UMP and GMP, UMP binding favored by 1 and GMP by 2. With 3, formation of mixed-ligand complexes was retarded by binding of two molecules of 3 to Pd2+. Full article
(This article belongs to the Special Issue Nucleoside Modifications) Printed Edition available
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Open AccessArticle Accumulation of Kaempferitrin and Expression of Phenyl-Propanoid Biosynthetic Genes in Kenaf (Hibiscus cannabinus)
Molecules 2014, 19(10), 16987-16997; doi:10.3390/molecules191016987
Received: 3 September 2014 / Revised: 8 October 2014 / Accepted: 15 October 2014 / Published: 23 October 2014
Cited by 5 | PDF Full-text (604 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Kenaf (Hibiscus cannabinus) is cultivated worldwide for its fiber; however, the medicinal properties of this plant are currently attracting increasing attention. In this study, we investigated the expression levels of genes involved in the biosynthesis of kaempferitrin, a compound with
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Kenaf (Hibiscus cannabinus) is cultivated worldwide for its fiber; however, the medicinal properties of this plant are currently attracting increasing attention. In this study, we investigated the expression levels of genes involved in the biosynthesis of kaempferitrin, a compound with many biological functions, in different kenaf organs. We found that phenylalanine ammonia lyase (HcPAL) was more highly expressed in stems than in other organs. Expression levels of cinnamate 4-hydroxylase (HcC4H) and 4-coumarate-CoA ligase (Hc4CL) were highest in mature leaves, followed by stems and young leaves, and lowest in roots and mature flowers. The expression of chalcone synthase (HcCHS), chalcone isomerase (HcCHI), and flavone 3-hydroxylase (HcF3H) was highest in young flowers, whereas that of flavone synthase (HcFLS) was highest in leaves. An analysis of kaempferitrin accumulation in the different organs of kenaf revealed that the accumulation of this compound was considerably higher (>10-fold) in leaves than in other organs. On the basis of a comparison of kaempferitrin contents with the expression levels of different genes in different organs, we speculate that HcFLS plays an important regulatory role in the kaempferitrin biosynthetic pathway in kenaf. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Structural Diversity of Copper(II) Complexes with N-(2-Pyridyl)Imidazolidin-2-Ones(Thiones) and Their in Vitro Antitumor Activity
Molecules 2014, 19(10), 17026-17051; doi:10.3390/molecules191017026
Received: 29 August 2014 / Revised: 30 September 2014 / Accepted: 13 October 2014 / Published: 23 October 2014
Cited by 6 | PDF Full-text (2038 KB) | HTML Full-text | XML Full-text
Abstract
Six series of structurally different mono- and binuclear copper(II) complexes 510 were obtained by reacting N-(2-pyridyl)imidazolidin-2-ones (1al), N,N'-bis(2-pyridyl)imidazolidin-2-ones (2a,b), N-acyl-N'(2-pyridyl)imidazolodin-2-ones (3aj) and
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Six series of structurally different mono- and binuclear copper(II) complexes 510 were obtained by reacting N-(2-pyridyl)imidazolidin-2-ones (1al), N,N'-bis(2-pyridyl)imidazolidin-2-ones (2a,b), N-acyl-N'(2-pyridyl)imidazolodin-2-ones (3aj) and N-(2-pyridyl)imidazolidine-2-thiones (4ag) with copper(II) chloride at an ambient temperature. The coordination modes of the complexes obtained were established by elemental analysis, IR spectroscopic data and single crystal X-ray diffraction studies. The in vitro cytotoxic activities of both the free ligands and copper(II) complexes were evaluated using a crystal violet microtiter plate assay on five human tumor cell lines: LCLC-103H, A-427, SISO, RT-4 and DAN-G. The free ligands 14 at concentration attainable in cancer cells of 20 μM showed no meaningful cytotoxic effect with cell viability in the range of 88%–100%. The most potent copper(II) complex of 1-(6-ethoxy-2-pyridyl)imidazolidin-2-one (6b) exhibited selective cytotoxicity against A-427 lung cancer cell line, while the complexes of 1-(5-methyl-2-pyridyl)imidazolidine-2-thione (5h) and 1-(4-tert-butyl-2-pyridyl)imidazolidine-2-thione (5j) showed cytostatic effect against a whole panel of five human tumor cell lines. In conclusion, the only complexes that showed remarkably increased activity in comparison to the free ligands were those obtained from N-(2-pyridyl)imidazolidine-2-thiones 4c and 4e substituted with alkyl group at position 4 or 5 of pyridine ring. Full article
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Open AccessArticle Ion Acceleration and D-D Nuclear Fusion in Laser-Generated Plasma from Advanced Deuterated Polyethylene
Molecules 2014, 19(10), 17052-17065; doi:10.3390/molecules191017052
Received: 17 July 2014 / Revised: 13 October 2014 / Accepted: 16 October 2014 / Published: 23 October 2014
Cited by 6 | PDF Full-text (1914 KB) | HTML Full-text | XML Full-text
Abstract
Deuterated polyethylene targets have been irradiated by means of a 1016 W/cm2 laser using 600 J pulse energy, 1315 nm wavelength, 300 ps pulse duration and 70 micron spot diameter. The plasma parameters were measured using on-line diagnostics based on ion
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Deuterated polyethylene targets have been irradiated by means of a 1016 W/cm2 laser using 600 J pulse energy, 1315 nm wavelength, 300 ps pulse duration and 70 micron spot diameter. The plasma parameters were measured using on-line diagnostics based on ion collectors, SiC detectors and plastic scintillators, all employed in time-of-flight configuration. In addition, a Thomson parabola spectrometer, an X-ray streak camera, and calibrated neutron dosimeter bubble detectors were employed. Characteristic protons and neutrons at maximum energies of 3.0 MeV and 2.45 MeV, respectively, were detected, confirming that energy spectra of reaction products coming from deuterium-deuterium nuclear fusion occur. In thick advanced targets a fusion rate of the order of 2 × 108 fusions per laser shot was calculated. Full article
(This article belongs to the Special Issue Deuterated Molecules and Polymers for Neutron Studies)

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Open AccessReview Quantum-Mechanical Calculations on Molecular Substructures Involved in Nanosystems
Molecules 2014, 19(10), 15468-15506; doi:10.3390/molecules191015468
Received: 2 July 2014 / Revised: 21 August 2014 / Accepted: 10 September 2014 / Published: 26 September 2014
Cited by 4 | PDF Full-text (5339 KB) | HTML Full-text | XML Full-text
Abstract
In this review article, four ideas are discussed: (a) aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b) polybenzene networks, from construction to energetic and
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In this review article, four ideas are discussed: (a) aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b) polybenzene networks, from construction to energetic and vibrational spectra computations; (c) quantum-mechanical calculations on the repeat units of various P-type crystal networks and (d) construction and stability evaluation, at DFTB level of theory, of some exotic allotropes of diamond D5, involved in hyper-graphenes. The overall conclusion was that several of the yet hypothetical molecular nanostructures herein described are serious candidates to the status of real molecules. Full article
(This article belongs to the Special Issue Quantum Information in Molecular Structures and Nanosystems)
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Open AccessReview Cellular Transport Mechanisms of Cytotoxic Metallodrugs: An Overview beyond Cisplatin
Molecules 2014, 19(10), 15584-15610; doi:10.3390/molecules191015584
Received: 5 August 2014 / Revised: 17 September 2014 / Accepted: 22 September 2014 / Published: 29 September 2014
Cited by 38 | PDF Full-text (997 KB) | HTML Full-text | XML Full-text
Abstract
The field of medicinal inorganic chemistry has grown consistently during the past 50 years; however, metal-containing coordination compounds represent only a minor proportion of drugs currently on the market, indicating that research in this area has not yet been thoroughly realized. Although platinum-based
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The field of medicinal inorganic chemistry has grown consistently during the past 50 years; however, metal-containing coordination compounds represent only a minor proportion of drugs currently on the market, indicating that research in this area has not yet been thoroughly realized. Although platinum-based drugs as cancer chemotherapeutic agents have been widely studied, exact knowledge of the mechanisms governing their accumulation in cells is still lacking. However, evidence suggests active uptake and efflux mechanisms are involved; this may be involved also in other experimental metal coordination and organometallic compounds with promising antitumor activities in vitro and in vivo, such as ruthenium and gold compounds. Such knowledge would be necessary to elucidate the balance between activity and toxicity profiles of metal compounds. In this review, we present an overview of the information available on the cellular accumulation of Pt compounds from in vitro, in vivo and clinical studies, as well as a summary of reports on the possible accumulation mechanisms for different families of experimental anticancer metal complexes (e.g., Ru Au and Ir). Finally, we discuss the need for rationalization of the investigational approaches available to study metallodrug cellular transport. Full article
(This article belongs to the Special Issue Practical Applications of Metal Complexes)
Open AccessReview Arbutus unedo L.: Chemical and Biological Properties
Molecules 2014, 19(10), 15799-15823; doi:10.3390/molecules191015799
Received: 21 July 2014 / Revised: 22 September 2014 / Accepted: 22 September 2014 / Published: 30 September 2014
Cited by 15 | PDF Full-text (806 KB) | HTML Full-text | XML Full-text
Abstract
Arbutus unedo L. (strawberry tree) has a circum-Mediterranean distribution, being found in western, central and southern Europe, north-eastern Africa (excluding Egypt and Libya) and the Canary Islands and western Asia. Fruits of the strawberry tree are generally used for preparing alcoholic drinks (wines,
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Arbutus unedo L. (strawberry tree) has a circum-Mediterranean distribution, being found in western, central and southern Europe, north-eastern Africa (excluding Egypt and Libya) and the Canary Islands and western Asia. Fruits of the strawberry tree are generally used for preparing alcoholic drinks (wines, liqueurs and brandies), jams, jellies and marmalades, and less frequently eaten as fresh fruit, despite their pleasing appearance. An overview of the chemical composition of different parts of the plant, strawberry tree honey and strawberry tree brandy will be presented. The biological properties of the different parts of A. unedo and strawberry tree honey will be also overviewed. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview A Starting Point for Fluorescence-Based Single-Molecule Measurements in Biomolecular Research
Molecules 2014, 19(10), 15824-15865; doi:10.3390/molecules191015824
Received: 21 July 2014 / Revised: 17 September 2014 / Accepted: 17 September 2014 / Published: 30 September 2014
Cited by 19 | PDF Full-text (2951 KB) | HTML Full-text | XML Full-text
Abstract
Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are
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Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are the obstacles on the way to a successful single-molecule microscopy experiment? In this review, we provide practical insights into fluorescence-based single-molecule experiments aiming for scientists who wish to take their experiments to the single-molecule level. We especially focus on fluorescence resonance energy transfer (FRET) experiments as these are a widely employed tool for the investigation of biomolecular mechanisms. We will guide the reader through the most critical steps that determine the success and quality of diffusion-based confocal and immobilization-based total internal reflection fluorescence microscopy. We discuss the specific chemical and photophysical requirements that make fluorescent dyes suitable for single-molecule fluorescence experiments. Most importantly, we review recently emerged photoprotection systems as well as passivation and immobilization strategies that enable the observation of fluorescently labeled molecules under biocompatible conditions. Moreover, we discuss how the optical single-molecule toolkit has been extended in recent years to capture the physiological complexity of a cell making it even more relevant for biological research. Full article
(This article belongs to the Special Issue Single Molecule Techniques)
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Open AccessReview Synthetic Advances in Macrosphelides: Natural Anticancer Agents
Molecules 2014, 19(10), 15982-16000; doi:10.3390/molecules191015982
Received: 11 August 2014 / Revised: 23 September 2014 / Accepted: 26 September 2014 / Published: 8 October 2014
Cited by 4 | PDF Full-text (2927 KB) | HTML Full-text | XML Full-text
Abstract
Total synthesis of macrosphelides is summarized. Synthetic approaches contain the preparation of key fragments and the final ring-closure reaction for unique 16- or 15-membered macrolactone skeletons. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessReview Resveratrol and Endothelial Nitric Oxide
Molecules 2014, 19(10), 16102-16121; doi:10.3390/molecules191016102
Received: 18 August 2014 / Revised: 21 September 2014 / Accepted: 25 September 2014 / Published: 9 October 2014
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Abstract
Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production
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Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Hydrogen Sulfide and Polysulfides as Biological Mediators
Molecules 2014, 19(10), 16146-16157; doi:10.3390/molecules191016146
Received: 16 September 2014 / Revised: 30 September 2014 / Accepted: 8 October 2014 / Published: 9 October 2014
Cited by 49 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogen sulfide (H2S) is recognized as a biological mediator with various roles such as neuromodulation, regulation of the vascular tone, cytoprotection, anti-inflammation, oxygen sensing, angiogenesis, and generation of mitochondrial energy. It is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and
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Hydrogen sulfide (H2S) is recognized as a biological mediator with various roles such as neuromodulation, regulation of the vascular tone, cytoprotection, anti-inflammation, oxygen sensing, angiogenesis, and generation of mitochondrial energy. It is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). The activity of CBS is enhanced by S-adenosyl methionine (SAM) and glutathionylation, while it is inhibited by nitric oxide (NO) and carbon monoxide (CO). The activity of CSE and cysteine aminotransferase (CAT), which produces the 3MST substrate 3-mercaptopyruvate (3MP), is regulated by Ca2+. H2S is oxidized to thiosulfate in mitochondria through the sequential action of sulfide quinone oxidoreductase (SQR), sulfur dioxygenase, and rhodanese. The rates of the production and clearance of H2S determine its cellular concentration. Polysulfides (H2Sn) have been found to occur in the brain and activate transient receptor potential ankyrin 1 (TRPA1) channels, facilitate the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus, and suppress the activity of phosphatase and tensin homolog (PTEN) by sulfurating (sulfhydrating) the target cysteine residues. A cross talk between H2S and NO also plays an important role in cardioprotection as well as regulation of the vascular tone. H2S, polysulfides, and their cross talk with NO may mediate various physiological and pathophysiological responses. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)
Open AccessReview Radical Addition to Iminium Ions and Cationic Heterocycles
Molecules 2014, 19(10), 16190-16222; doi:10.3390/molecules191016190
Received: 28 August 2014 / Revised: 22 September 2014 / Accepted: 22 September 2014 / Published: 10 October 2014
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Abstract
Carbon-centered radicals represent highly useful reactive intermediates in organic synthesis. Their nucleophilic character is reflected by fast additions to electron deficient C=X double bonds as present in iminium ions or cationic heterocycles. This review covers diverse reactions of preformed or in situ-generated
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Carbon-centered radicals represent highly useful reactive intermediates in organic synthesis. Their nucleophilic character is reflected by fast additions to electron deficient C=X double bonds as present in iminium ions or cationic heterocycles. This review covers diverse reactions of preformed or in situ-generated cationic substrates with various types of C-radicals, including alkyl, alkoxyalkyl, trifluoromethyl, aryl, acyl, carbamoyl, and alkoxycarbonyl species. Despite its high reactivity, the strong interaction of the radical’s SOMO with the LUMO of the cation frequently results in a high regioselectivity. Intra- and intermolecular processes such as the Minisci reaction, the Porta reaction, and the Knabe rearrangement will be discussed along with transition metal and photoredox catalysis or electrochemical methods to generate the odd-electron species. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)
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Open AccessReview Flavonoids as Important Molecules of Plant Interactions with the Environment
Molecules 2014, 19(10), 16240-16265; doi:10.3390/molecules191016240
Received: 30 May 2014 / Revised: 15 September 2014 / Accepted: 16 September 2014 / Published: 10 October 2014
Cited by 63 | PDF Full-text (1257 KB) | HTML Full-text | XML Full-text
Abstract
Flavonoids are small molecular secondary metabolites synthesized by plants with various biological activities. Due to their physical and biochemical properties, they are capable of participating in plants’ interactions with other organisms (microorganisms, animals and other plants) and their reactions to environmental stresses. The
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Flavonoids are small molecular secondary metabolites synthesized by plants with various biological activities. Due to their physical and biochemical properties, they are capable of participating in plants’ interactions with other organisms (microorganisms, animals and other plants) and their reactions to environmental stresses. The majority of their functions result from their strong antioxidative properties. Although an increasing number of studies focus on the application of flavonoids in medicine or the food industry, their relevance for the plants themselves also deserves extensive investigations. This review summarizes the current knowledge on the functions of flavonoids in the physiology of plants and their relations with the environment. Full article
Open AccessReview Unraveling the Photocatalytic Mechanisms on TiO2 Surfaces Using the Oxygen-18 Isotopic Label Technique
Molecules 2014, 19(10), 16291-16311; doi:10.3390/molecules191016291
Received: 5 August 2014 / Revised: 24 September 2014 / Accepted: 6 October 2014 / Published: 10 October 2014
Cited by 7 | PDF Full-text (590 KB) | HTML Full-text | XML Full-text
Abstract
During the last several decades TiO2 photocatalytic oxidation using the molecular oxygen in air has emerged as a promising method for the degradation of recalcitrant organic pollutants and selective transformations of valuable organic chemicals. Despite extensive studies, the mechanisms of these photocatalytic
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During the last several decades TiO2 photocatalytic oxidation using the molecular oxygen in air has emerged as a promising method for the degradation of recalcitrant organic pollutants and selective transformations of valuable organic chemicals. Despite extensive studies, the mechanisms of these photocatalytic reactions are still poorly understood due to their complexity. In this review, we will highlight how the oxygen-18 isotope labeling technique can be a powerful tool to elucidate complicated photocatalytic mechanisms taking place on the TiO2 surface. To this end, the application of the oxygen-18 isotopic-labeling method to three representative photocatalytic reactions is discussed: (1) the photocatalytic hydroxylation of aromatics; (2) oxidative cleavage of aryl rings on the TiO2 surface; and (3) photocatalytic decarboxylation of saturated carboxylic acids. The results show that the oxygen atoms of molecular oxygen can incorporate into the corresponding products in aqueous solution in all three of these reactions, but the detailed incorporation pathways are completely different in each case. For the hydroxylation process, the O atom in O2 is shown to be incorporated through activation of O2 by conduction band electrons. In the cleavage of aryl rings, O atoms are inserted into the aryl ring through the site-dependent coordination of reactants on the TiO2 surface. A new pathway for the decarboxylation of saturated carboxylic acids with pyruvic acid as an intermediate is identified, and the O2 is incorporated into the products through the further oxidation of pyruvic acid by active species from the activation of O2 by conduction band electrons. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessReview Structural Formation and Photocatalytic Activity of Magnetron Sputtered Titania and Doped-Titania Coatings
Molecules 2014, 19(10), 16327-16348; doi:10.3390/molecules191016327
Received: 27 August 2014 / Revised: 25 September 2014 / Accepted: 2 October 2014 / Published: 13 October 2014
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Abstract
Titania and doped-titania coatings can be deposited by a wide range of techniques; this paper will concentrate on magnetron sputtering techniques, including “conventional” reactive co-sputtering from multiple metal targets and the recently introduced high power impulse magnetron sputtering (HiPIMS). The latter has been
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Titania and doped-titania coatings can be deposited by a wide range of techniques; this paper will concentrate on magnetron sputtering techniques, including “conventional” reactive co-sputtering from multiple metal targets and the recently introduced high power impulse magnetron sputtering (HiPIMS). The latter has been shown to deliver a relatively low thermal flux to the substrate, whilst still allowing the direct deposition of crystalline titania coatings and, therefore, offers the potential to deposit photocatalytically active titania coatings directly onto thermally sensitive substrates. The deposition of coatings via these techniques will be discussed, as will the characterisation of the coatings by XRD, SEM, EDX, optical spectroscopy, etc. The assessment of photocatalytic activity and photoactivity through the decomposition of an organic dye (methylene blue), the inactivation of E. coli microorganisms and the measurement of water contact angles will be described. The impact of different deposition technologies, doping and co-doping strategies on coating structure and activity will be also considered. Full article
(This article belongs to the Special Issue Photocatalysis) Printed Edition available
Open AccessReview Bioactivity and Chemical Synthesis of Caffeic Acid Phenethyl Ester and Its Derivatives
Molecules 2014, 19(10), 16458-16476; doi:10.3390/molecules191016458
Received: 15 September 2014 / Revised: 3 October 2014 / Accepted: 9 October 2014 / Published: 13 October 2014
Cited by 18 | PDF Full-text (272 KB) | HTML Full-text | XML Full-text
Abstract
Caffeic acid phenethyl ester (CAPE), as one of the main active ingredients of the natural product propolis, shows the unique biological activities such as anti-tumor, anti-oxidation, anti-inflammatory, immune regulation, and so on. These have attracted the attention of many researchers to explore the
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Caffeic acid phenethyl ester (CAPE), as one of the main active ingredients of the natural product propolis, shows the unique biological activities such as anti-tumor, anti-oxidation, anti-inflammatory, immune regulation, and so on. These have attracted the attention of many researchers to explore the compound with potent biological activities. This review aims to summarize its bioactivities, synthetic methods and derivatives, which will be helpful for further study and development of CAPE and its derivatives. Full article
Open AccessReview Diversity-Oriented Synthesis as a Tool for Chemical Genetics
Molecules 2014, 19(10), 16506-16528; doi:10.3390/molecules191016506
Received: 22 August 2014 / Revised: 30 September 2014 / Accepted: 1 October 2014 / Published: 14 October 2014
Cited by 10 | PDF Full-text (1488 KB) | HTML Full-text | XML Full-text
Abstract
Chemical genetics is an approach for identifying small molecules with the ability to induce a biological phenotype or to interact with a particular gene product, and it is an emerging tool for lead generation in drug discovery. Accordingly, there is a need for
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Chemical genetics is an approach for identifying small molecules with the ability to induce a biological phenotype or to interact with a particular gene product, and it is an emerging tool for lead generation in drug discovery. Accordingly, there is a need for efficient and versatile synthetic processes capable of generating complex and diverse molecular libraries, and Diversity-Oriented Synthesis (DOS) of small molecules is the concept of choice to give access to new chemotypes with high chemical diversity. In this review, the combination of chemical genetics and diversity-oriented synthesis to identify new chemotypes as hit compounds in chemical biology and drug discovery is reported, giving an overview of basic concepts and selected case studies. Full article
(This article belongs to the Special Issue Recent Advances in Diversity-Oriented Synthesis)
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Open AccessReview New Developments in Spin Labels for Pulsed Dipolar EPR
Molecules 2014, 19(10), 16998-17025; doi:10.3390/molecules191016998
Received: 1 September 2014 / Revised: 7 October 2014 / Accepted: 13 October 2014 / Published: 23 October 2014
Cited by 12 | PDF Full-text (414 KB) | HTML Full-text | XML Full-text
Abstract
Spin labelling is a chemical technique that enables the integration of a molecule containing an unpaired electron into another framework for study. Given the need to understand the structure, dynamics, and conformational changes of biomacromolecules, spin labelling provides a relatively non-intrusive technique and
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Spin labelling is a chemical technique that enables the integration of a molecule containing an unpaired electron into another framework for study. Given the need to understand the structure, dynamics, and conformational changes of biomacromolecules, spin labelling provides a relatively non-intrusive technique and has certain advantages over X-ray crystallography; which requires high quality crystals. The technique relies on the design of binding probes that target a functional group, for example, the thiol group of a cysteine residue within a protein. The unpaired electron is typically supplied through a nitroxide radical and sterically shielded to preserve stability. Pulsed electron paramagnetic resonance (EPR) techniques allow small magnetic couplings to be measured (e.g., <50 MHz) providing information on single label probes or the dipolar coupling between multiple labels. In particular, distances between spin labels pairs can be derived which has led to many protein/enzymes and nucleotides being studied. Here, we summarise recent examples of spin labels used for pulse EPR that serve to illustrate the contribution of chemistry to advancing discoveries in this field. Full article
(This article belongs to the Special Issue Free Radicals and Radical Ions)

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Open AccessConcept Paper Modern Prodrug Design for Targeted Oral Drug Delivery
Molecules 2014, 19(10), 16489-16505; doi:10.3390/molecules191016489
Received: 12 September 2014 / Revised: 7 October 2014 / Accepted: 8 October 2014 / Published: 14 October 2014
Cited by 18 | PDF Full-text (1207 KB) | HTML Full-text | XML Full-text
Abstract
The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and
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The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options. Full article
(This article belongs to the Special Issue Prodrugs)
Open AccessRetraction Retraction: Beltaïef et al. An Expeditious Synthesis of [1,2]Isoxazolidin-5-ones and [1,2]Oxazin-6-ones from Functional Allyl Bromide Derivatives. Molecules 2010, 15, 4094-4101
Molecules 2014, 19(10), 16810; doi:10.3390/molecules191016810
Received: 9 October 2014 / Accepted: 17 October 2014 / Published: 17 October 2014
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Abstract
We have been made aware that the figures, tables, compounds and experimental data reported in the title paper [1] are duplicated in another publication by the same authors [2]. [...] Full article
(This article belongs to the Section Organic Synthesis)
Open AccessLetter Efficient Synthesis of Kinsenoside and Goodyeroside A by a Chemo-Enzymatic Approach
Molecules 2014, 19(10), 16950-16958; doi:10.3390/molecules191016950
Received: 24 September 2014 / Revised: 12 October 2014 / Accepted: 15 October 2014 / Published: 22 October 2014
Cited by 4 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Kinsenoside (1) and goodyeroside A (2), two naturally occurring stereoisomers with diverse biological activities, have been synthesized efficiently by a chemo-enzymatic approach with a total yield of 12.7%. The aglycones, (R)- and (S)-3-hydroxy-γ-butyrolactone, were prepared
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Kinsenoside (1) and goodyeroside A (2), two naturally occurring stereoisomers with diverse biological activities, have been synthesized efficiently by a chemo-enzymatic approach with a total yield of 12.7%. The aglycones, (R)- and (S)-3-hydroxy-γ-butyrolactone, were prepared from D- and L-malic acid by a four-step chemical approach with a yield of 75%, respectively. These butyrolactones were then successfully glycosidated using β-D-glucosidase as a catalyst in a homogeneous organic-water system. Under the optimized enzymatic conditions, the yields of kinsenoside and goodyeroside A in the enzymatic steps both reached 16.8%. Full article
(This article belongs to the Section Organic Synthesis)
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