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Molecules, Volume 20, Issue 11 (November 2015), Pages 19647-20966

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Open AccessArticle Optimization of Antifungal Extracts from Ficus hirta Fruits Using Response Surface Methodology and Antifungal Activity Tests
Molecules 2015, 20(11), 19647-19659; doi:10.3390/molecules201119648
Received: 2 September 2015 / Revised: 14 October 2015 / Accepted: 15 October 2015 / Published: 29 October 2015
Cited by 3 | PDF Full-text (4507 KB) | HTML Full-text | XML Full-text
Abstract
The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio
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The fruits of Ficus hirta (FH) display strong antifungal activity against Penicillium italicum and Penicillium digitatum. In order to optimize the extraction conditions of antifungal extracts from FH fruit, various extraction parameters, such as ethanol concentration, extraction time, solvent to solid ratio and temperature, were chosen to identify their effects on the diameters of inhibition zones (DIZs) against these two Penicillium molds. Response surface methodology (RSM) was applied to obtain the optimal combination of these parameters. Results showed that the optimal extraction parameters for maximum antifungal activity were: 90% (v/v) ethanol concentration, 65 min extraction time, 31 mL/g solvent to solid ratio and 51 °C temperature. Under the abovementioned extraction conditions, the experimental DIZs values obtained experimentally were 57.17 ± 0.75 and 39.33 ± 0.82 mm, which were very close to the values of 57.26 and 39.29 mm predicted by the model. Further, nine kinds of phytopathogens were tested in vitro to explore the antifungal activity of the FH extracts. It was found for the first time that the FH extracts showed significant inhibition on the growth of P. italicum, A. citri, P. vexans, P. cytosporella and P. digitatum. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers
Molecules 2015, 20(11), 19660-19673; doi:10.3390/molecules201119649
Received: 27 August 2015 / Revised: 12 October 2015 / Accepted: 20 October 2015 / Published: 29 October 2015
Cited by 5 | PDF Full-text (341 KB) | HTML Full-text | XML Full-text
Abstract
Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (−)-cis-EC, (+)-trans-EC, and (−)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg)
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Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (−)-cis-EC, (+)-trans-EC, and (−)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES) test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+) and (−)-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+) and (−)-trans-EC (at 300 mg/kg) showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+)-cis-EC and (+)-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+)-cis-EC, (+)-trans-EC, and (−)-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle X-ray Crystallography, DFT Calculations and Molecular Docking of Indole-Arylpiperazine Derivatives as α1A-Adrenoceptor Antagonists
Molecules 2015, 20(11), 19674-19689; doi:10.3390/molecules201119651
Received: 14 September 2015 / Accepted: 16 October 2015 / Published: 30 October 2015
Cited by 4 | PDF Full-text (3570 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Indole-arylpiperazine derivatives have exhibited good selectivity for the α1A-adrenoceptor, but the structure-activity-binding mechanism relationship remains unclear. In the current study, three compounds (1, 2 and 3) were investigated through single-crystal X-ray diffraction analysis, density functional theory (DFT) calculations
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Indole-arylpiperazine derivatives have exhibited good selectivity for the α1A-adrenoceptor, but the structure-activity-binding mechanism relationship remains unclear. In the current study, three compounds (1, 2 and 3) were investigated through single-crystal X-ray diffraction analysis, density functional theory (DFT) calculations and molecular docking using a homology model of the α1A receptor. Compounds 1 and 3 form H-bonds networks to stabilize their three-dimensional structures, while C–H···π interactions play a significant role in the packing of 2. Based on DFT-optimized conformations, the HOMO-LUMO energy gaps and molecular electrostatic potential (MEP) were theoretically calculated at the B3LYP/6-311G (d, p) level of theory. Chemical reactivity increases in the order of 3 < 2 < 1, and the maximum positive region of the MEP maps is mainly localized over the NH group. The binding mechanisms of ligand-α1A-adrenoceptor complexes were illustrated by molecular docking. Binding to Gln177 of the second extracellular loop region via hydrogen bonds is likely to be essential for α1A-selective antagonists. The present work sheds light on the studies of structure-activity-binding mechanism and aids in the design of α1A antagonists with high selectivity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli
Molecules 2015, 20(11), 19690-19698; doi:10.3390/molecules201119650
Received: 14 August 2015 / Revised: 21 October 2015 / Accepted: 22 October 2015 / Published: 30 October 2015
Cited by 7 | PDF Full-text (2155 KB) | HTML Full-text | XML Full-text
Abstract
Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections.
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Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. Furthermore, TC-controlled transcriptional regulation systems (Tet-on and Tet-off) are useful for controlling transgene expression in vitro and in vivo for biomedical research purposes; controlled TC release systems could be useful here, as well. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile crystalline material 41 (MCM-41), a type of MSN, has a mesoporous structure with pores forming channels in a hexagonal fashion. We prepared 41 ± 4 and 406 ± 55 nm MCM-41 mesoporous silica nanoparticles and loaded TC for controlled dug release; TC content in the TC-MCM-41 nanoparticles was 18.7% and 17.7% w/w, respectively. Release of TC from TC-MCM-41 nanoparticles was then measured in phosphate-buffered saline (PBS), pH 7.2, at 37 °C over a period of 5 h. Most antibiotic was released from both over this observation period; however, the majority of TC was released over the first hour. Efficacy of the TC-MCM-41 nanoparticles was then shown to be superior to free TC against Escherichia coli (E. coli) in culture over a 24 h period, while blank nanoparticles had no effect. Full article
(This article belongs to the collection Nanomedicine)
Open AccessArticle Anticancer and Antibacterial Activity Studies of Gold(I)-Alkynyl Chromones
Molecules 2015, 20(11), 19699-19718; doi:10.3390/molecules201119647
Received: 8 September 2015 / Revised: 18 October 2015 / Accepted: 23 October 2015 / Published: 30 October 2015
Cited by 2 | PDF Full-text (2958 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three gold(I) complexes of alkynyl chromones were synthesized and characterized. The single-crystal X-ray structure analysis of a dinuclear compound and of a flavone derivative exhibit a typical d10 gold(I)-alkynyl linear arrangement. All complexes were evaluated as anticancer and antibacterial agents against four human
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Three gold(I) complexes of alkynyl chromones were synthesized and characterized. The single-crystal X-ray structure analysis of a dinuclear compound and of a flavone derivative exhibit a typical d10 gold(I)-alkynyl linear arrangement. All complexes were evaluated as anticancer and antibacterial agents against four human cancer cell lines and four pathogenic bacterial strains. All compounds show antiproliferative activity at lower micromolar range concentrations. Complex 4 showed a broad activity profile, being more active than the reference drug auranofin against HepG2, MCF-7 and CCRF-CEM cancer cells. The cellular uptake into MCF-7 cells of the investigated complexes was measured by atomic absorption spectroscopy (AAS). These measurements showed a positive correlation between an increased cellular gold content and the incubation time of the complexes. Unexpectedly an opposite effect was observed for the most active compound. Biological assays revealed various molecular mechanisms for these compounds, comprising: (i) thioredoxin reductase (TrxR) inhibition, (ii) caspases-9 and -3 activation; (iii) DNA damaging activity and (iv) cell cycle disturbance. The gold(I) complexes were also bactericidal against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacterial strains, while showing no activity against the Gram-negative Escherichia coli bacterial strain. Full article
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Open AccessArticle Chemotaxonomic Metabolite Profiling of 62 Indigenous Plant Species and Its Correlation with Bioactivities
Molecules 2015, 20(11), 19719-19734; doi:10.3390/molecules201119652
Received: 28 August 2015 / Revised: 22 October 2015 / Accepted: 23 October 2015 / Published: 2 November 2015
Cited by 4 | PDF Full-text (2290 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC)-linear trap quadrupole-ion trap (LTQ-IT) mass spectrometry/mass spectrometry (MS/MS) combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA), the 62 species clustered depending on
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Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC)-linear trap quadrupole-ion trap (LTQ-IT) mass spectrometry/mass spectrometry (MS/MS) combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA), the 62 species clustered depending on their phylogenetic family, in particular, Aceraceae, Betulaceae, and Fagaceae were distinguished from Rosaceae, Fabaceae, and Asteraceae. Quinic acid, gallic acid, quercetin, quercetin derivatives, kaempferol, and kaempferol derivatives were identified as family-specific metabolites, and were found in relatively high concentrations in Aceraceae, Betulaceae, and Fagaceae. Fagaceae and Asteraceae were selected based on results of PLS-DA and bioactivities to determine the correlation between metabolic differences among plant families and bioactivities. Quinic acid, quercetin, kaempferol, quercetin derivatives, and kaempferol derivatives were found in higher concentrations in Fagaceae than in Asteraceae, and were positively correlated with antioxidant and tyrosinase inhibition activities. These results suggest that metabolite profiling was a useful tool for finding the different metabolic states of each plant family and understanding the correlation between metabolites and bioactivities in accordance with plant family. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Drug Discovery of Host CLK1 Inhibitors for Influenza Treatment
Molecules 2015, 20(11), 19735-19747; doi:10.3390/molecules201119653
Received: 11 August 2015 / Revised: 28 September 2015 / Accepted: 21 October 2015 / Published: 2 November 2015
Cited by 2 | PDF Full-text (3279 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential
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The rapid evolution of influenza virus makes antiviral drugs less effective, which is considered to be a major bottleneck in antiviral therapy. The key proteins in the host cells, which are related with the replication cycle of influenza virus, are regarded as potential drug targets due to their distinct advantage of lack of evolution and drug resistance. Cdc2-like kinase 1 (CLK1) in the host cells is responsible for alternative splicing of the M2 gene of influenza virus during influenza infection and replication. In this study, we carried out baculovirus-mediated expression and purification of CLK1 and established a reliable screening assay for CLK1 inhibitors. After a virtual screening of CLK1 inhibitors was performed, the activities of the selected compounds were evaluated. Finally, several compounds with strong inhibitory activity against CLK1 were discovered and their in vitro anti-influenza virus activities were validated using a cytopathic effect (CPE) reduction assay. The assay results showed that clypearin, corilagin, and pinosylvine were the most potential anti-influenza virus compounds as CLK1 inhibitors among the compounds tested. These findings will provide important information for new drug design and development in influenza treatment, and CLK1 may be a potent drug target for anti-influenza drug screening and discovery. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Shuidouchi (Fermented Soybean) Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury
Molecules 2015, 20(11), 19748-19763; doi:10.3390/molecules201119654
Received: 8 October 2015 / Accepted: 20 October 2015 / Published: 2 November 2015
Cited by 3 | PDF Full-text (3569 KB) | HTML Full-text | XML Full-text
Abstract
Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS
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Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS (glass vessel fermented Shuidouchi) had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL) and pH of gastric juice (3.1) of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL), gastrin (Gas) level and increase somatostatin (SS), vasoactive intestinal peptide (VIP) level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD), nitric oxide (NO) and malonaldehyde (MDA) contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Optimization of Extraction Condition of Bee Pollen Using Response Surface Methodology: Correlation between Anti-Melanogenesis, Antioxidant Activity, and Phenolic Content
Molecules 2015, 20(11), 19764-19774; doi:10.3390/molecules201119656
Received: 8 September 2015 / Revised: 19 October 2015 / Accepted: 20 October 2015 / Published: 2 November 2015
Cited by 5 | PDF Full-text (1057 KB) | HTML Full-text | XML Full-text
Abstract
Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such
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Bee pollen is flower pollen with nectar and salivary substances of bees and rich in essential components. Bee pollen showed antioxidant and tyrosinase inhibitory activity in our assay system. To maximize the antioxidant and tyrosinase inhibitory activity of bee pollen, extraction conditions, such as extraction solvent, extraction time, and extraction temperature, were optimized using response surface methodology. Regression analysis showed a good fit of this model and yielded the second-order polynomial regression for tyrosinase inhibition and antioxidant activity. Among the extraction variables, extraction solvent greatly affected the activity. The optimal condition was determined as EtOAc concentration in MeOH, 69.6%; temperature, 10.0 °C; and extraction time, 24.2 h, and the tyrosinase inhibitory and antioxidant activity under optimal condition were found to be 57.9% and 49.3%, respectively. Further analysis showed the close correlation between activities and phenolic content, which suggested phenolic compounds are active constituents of bee pollen for tyrosinase inhibition and antioxidant activity. Taken together, these results provide useful information about bee pollen as cosmetic therapeutics to reduce oxidative stress and hyperpigmentation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antihypertensive Effects of Artemisia scoparia Waldst in Spontaneously Hypertensive Rats and Identification of Angiotensin I Converting Enzyme Inhibitors
Molecules 2015, 20(11), 19789-19804; doi:10.3390/molecules201119657
Received: 22 June 2015 / Revised: 26 October 2015 / Accepted: 27 October 2015 / Published: 3 November 2015
Cited by 5 | PDF Full-text (2019 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic
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We investigated the antihypertensive effects of Artemisia scoparia (AS) in spontaneously hypertensive rats (SHR). The rats were fed diets containing 2% (w/w) hot water extracts of AS aerial parts for 6 weeks. The AS group had significantly lower systolic and diastolic blood pressure levels than the control group. The AS group also had lower angiotensin I converting enzyme (ACE) activity and angiotensin II content in serum compared to the control group. The AS group showed higher vascular endothelial growth factor and lower ras homolog gene family member A expression levels in kidney compared to the control group. The AS group had significantly lower levels of plasma lipid oxidation and protein carbonyls than the control group. One new and six known compounds were isolated from AS by guided purification. The new compound was determined to be 4′-O-β-D-glucopyranoyl (E)-4-hydroxy-3-methylbut-2-enyl benzoate, based on its nuclear magnetic resonance and electrospray ionization-mass spectroscopy data. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Synthesis, Characterization and Biological Evaluation of Some Quinoxaline Derivatives: A Promising and Potent New Class of Antitumor and Antimicrobial Agents
Molecules 2015, 20(11), 19805-19822; doi:10.3390/molecules201119655
Received: 13 August 2015 / Revised: 22 October 2015 / Accepted: 26 October 2015 / Published: 3 November 2015
Cited by 5 | PDF Full-text (841 KB) | HTML Full-text | XML Full-text
Abstract
In continuation of our endeavor towards the development of potent and effective anticancer and antimicrobial agents; the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4-triazoloquinoxalines. These compounds were synthesized via
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In continuation of our endeavor towards the development of potent and effective anticancer and antimicrobial agents; the present work deals with the synthesis of some novel tetrazolo[1,5-a]quinoxalines, N-pyrazoloquinoxalines, the corresponding Schiff bases, 1,2,4-triazinoquinoxalines and 1,2,4-triazoloquinoxalines. These compounds were synthesized via the reaction of the key intermediate hydrazinoquinoxalines with various reagents and evaluated for anticancer and antimicrobial activity. The results indicated that tetrazolo[1,5-a]quinoxaline derivatives showed the best result, with the highest inhibitory effects towards the three tested tumor cell lines, which were higher than that of the reference doxorubicin and these compounds were non-cytotoxic to normal cells (IC50 values > 100 μg/mL). Also, most of synthesized compounds exhibited the highest degrees of inhibition against the tested strains of Gram positive and negative bacteria, so tetrazolo[1,5-a]quinoxaline derivatives show dual activity as anticancer and antimicrobial agents. Full article
(This article belongs to the Section Bioorganic Chemistry)
Open AccessArticle Anti-Inflammatory Activity Comparison among Scropoliosides—Catalpol Derivatives with 6-O-Substituted Cinnamyl Moieties
Molecules 2015, 20(11), 19823-19836; doi:10.3390/molecules201119659
Received: 11 September 2015 / Revised: 30 September 2015 / Accepted: 7 October 2015 / Published: 3 November 2015
Cited by 3 | PDF Full-text (3809 KB) | HTML Full-text | XML Full-text
Abstract
We have previously shown that scropolioside B has higher anti-inflammatory activity than catalpol does after the inhibition of nuclear factor (NF)-κB activity and IL-1β expression, maturation, and secretion. Various scropoliosides were extracted, isolated, and purified from Scrophularia dentata Royle ex Benth. We then
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We have previously shown that scropolioside B has higher anti-inflammatory activity than catalpol does after the inhibition of nuclear factor (NF)-κB activity and IL-1β expression, maturation, and secretion. Various scropoliosides were extracted, isolated, and purified from Scrophularia dentata Royle ex Benth. We then compared their anti-inflammatory activities against LPS-induced NF-κB activity, cytokines mRNA expression, IL-1β secretion, and cyclooxygenase-2 activity. The inhibitory effects of the scropoliosides varied depending on whether the 6-O-substituted cinnamyl moiety was linked to C′′ 2-OH, C′′3-OH, or C′′4-OH, and on the number of moieties linked, which is closely related to the enhancement of antiinflammatory activity. Among these compounds, scropolioside B had the strongest antiinflammatory effects. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates—Bioinspired Sulfoxidation Catalysts
Molecules 2015, 20(11), 19837-19848; doi:10.3390/molecules201119667
Received: 21 September 2015 / Revised: 13 October 2015 / Accepted: 14 October 2015 / Published: 4 November 2015
Cited by 1 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A click chemistry approach based on the reaction between alkynylflavins and mono(6-azido-6-deoxy)-β-cyclodextrin has proven to be a useful tool for the synthesis of flavin-cyclodextrin conjugates studied as monooxygenase mimics in enantioselective sulfoxidations. Full article
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Open AccessArticle Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates
Molecules 2015, 20(11), 19849-19864; doi:10.3390/molecules201119664
Received: 9 September 2015 / Revised: 20 October 2015 / Accepted: 21 October 2015 / Published: 4 November 2015
Cited by 6 | PDF Full-text (1806 KB) | HTML Full-text | XML Full-text
Abstract
Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were
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Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX) was attached to the N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5–5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates. Full article
(This article belongs to the collection Nanomedicine)
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Open AccessArticle Polyphenolic Compositions and Chromatic Characteristics of Bog Bilberry Syrup Wines
Molecules 2015, 20(11), 19865-19877; doi:10.3390/molecules201119662
Received: 21 September 2015 / Revised: 22 October 2015 / Accepted: 27 October 2015 / Published: 4 November 2015
Cited by 7 | PDF Full-text (356 KB) | HTML Full-text | XML Full-text
Abstract
Phenolic compounds determine the color quality of fruit wines. In this study, the phenolic compound content and composition, color characteristics and changes during 6 months of bottle aging were studied in wines fermented with bog bilberry syrup under three different pHs. The total
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Phenolic compounds determine the color quality of fruit wines. In this study, the phenolic compound content and composition, color characteristics and changes during 6 months of bottle aging were studied in wines fermented with bog bilberry syrup under three different pHs. The total anthocyanins and total phenols were around 15.12–16.23 mg/L and 475.82 to 486.50 mg GAE/L in fresh wines and declined 22%–31% and about 11% in bottle aged wines, respectively. In fresh wines, eight anthocyanins, six phenolic aids and 14 flavonols, but no flavon-3-ols were identified; Malvidin-3-O-glucoside, petunidin-3-O-glucoside and delphinium-3-O-glucoside were the predominant pigments; Chlorogentic acid was the most abundant phenolic acid, and quercetin-3-O-galactoside and myricetin-3-O-galactoside accounted for nearly 90% of the total flavonols. During 6 months of bottle storage, the amounts of all the monomeric anthocyanins and phenolic acids were reduced dramatically, while the glycosidyl flavonols remained constant or were less reduced and their corresponding aglycones increased a lot. The effects of aging on blueberry wine color were described as the loss of color intensity with a dramatic change in color hue, from initial red-purple up to final red-brick nuances, while the pH of the fermentation matrix was negatively related to the color stability of aged wine. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Long-Term Lithium Treatment Increases cPLA2 and iPLA2 Activity in Cultured Cortical and Hippocampal Neurons
Molecules 2015, 20(11), 19878-19885; doi:10.3390/molecules201119663
Received: 13 August 2015 / Revised: 12 October 2015 / Accepted: 19 October 2015 / Published: 4 November 2015
Cited by 5 | PDF Full-text (539 KB) | HTML Full-text | XML Full-text
Abstract
Background: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium
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Background: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. Objective: To investigate the effect of lithium on cytosolic phospholipase A2 (PLA2) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer’s disease (AD). Methods: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA2 and two PLA2 subtypes: cytosolic calcium-dependent (cPLA2); and calcium-independent (iPLA2). Results: cPLA2 activity increased by 82% (0.02 mM; p = 0.05) and 26% (0.2 mM; p = 0.04) in cortical neurons and by 61% (0.2 mM; p = 0.03) and 57% (2 mM; p = 0.04) in hippocampal neurons. iPLA2 activity was increased by 7% (0.2 mM; p = 0.04) and 13% (2 mM; p = 0.05) in cortical neurons and by 141% (0.02 mM; p = 0.0198) in hippocampal neurons. Conclusion: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA2. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA2 subtypes is tissue specific, i.e., iPLA2 in hippocampal neurons, and cPLA2 in cortical neurons. Because PLA2 activities are reported to be reduced in Alzheimer’s disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
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Open AccessArticle Photostabilizing Efficiency of PVC in the Presence of Schiff Bases as Photostabilizers
Molecules 2015, 20(11), 19886-19899; doi:10.3390/molecules201119665
Received: 18 August 2015 / Revised: 4 October 2015 / Accepted: 8 October 2015 / Published: 4 November 2015
Cited by 2 | PDF Full-text (3533 KB) | HTML Full-text | XML Full-text
Abstract
The photostabilization of polyvinyl chloride (PVC) films by Schiff bases was investigated. Polyvinyl chloride films containing 0.5 wt % Schiff bases were produced using the same casting method as that used for additive-free PVC films from tetrahydrofuran (THF) solvent. The photostabilization activities of
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The photostabilization of polyvinyl chloride (PVC) films by Schiff bases was investigated. Polyvinyl chloride films containing 0.5 wt % Schiff bases were produced using the same casting method as that used for additive-free PVC films from tetrahydrofuran (THF) solvent. The photostabilization activities of these compounds were determined by monitoring the carbonyl, polyene and hydroxyl indices with irradiation time. The changes in viscosity average molecular weight of PVC with irradiation time were also monitored using THF as a solvent. The quantum yield of chain scission (Φcs) for the studied complexes in PVC was estimated to range between 4.72 and 8.99 × 10−8. According to the experimental results, several mechanisms were suggested, depending on the structure of the additive. Ultra violet (UV) absorption, peroxide decomposition and radical scavenging were suggested as the photostabilizing mechanisms. Full article
(This article belongs to the Section Photochemistry)
Open AccessArticle Hazardous Doping for Photo-Electrochemical Conversion: The Case of Nb-Doped Fe2O3 from First Principles
Molecules 2015, 20(11), 19900-19906; doi:10.3390/molecules201119668
Received: 2 October 2015 / Revised: 26 October 2015 / Accepted: 26 October 2015 / Published: 4 November 2015
Cited by 13 | PDF Full-text (1941 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The challenge of improving the efficiency of photo-electrochemical devices is often addressed through doping. However, this strategy could harm performance. Specifically, as demonstrated in a recent experiment, doping one of the most widely used materials for water splitting, iron (III) oxide (Fe2
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The challenge of improving the efficiency of photo-electrochemical devices is often addressed through doping. However, this strategy could harm performance. Specifically, as demonstrated in a recent experiment, doping one of the most widely used materials for water splitting, iron (III) oxide (Fe2O3), with niobium (Nb) can still result in limited efficiency. In order to better understand the hazardous effect of doping, we use Density Functional Theory (DFT)+U for the case of Nb-doped Fe2O3. We find a direct correlation between the charge of the dopant, the charge on surface of the Fe2O3 material, and the overpotential required for water oxidation reaction. We believe that this work contributes to advancing our understanding of how to select effective dopants for materials. Full article
(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
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Open AccessCommunication Radical Scavenging by Acetone: A New Perspective to Understand Laccase/ABTS Inactivation and to Recover Redox Mediator
Molecules 2015, 20(11), 19907-19913; doi:10.3390/molecules201119672
Received: 30 July 2015 / Revised: 27 October 2015 / Accepted: 28 October 2015 / Published: 4 November 2015
Cited by 5 | PDF Full-text (1000 KB) | HTML Full-text | XML Full-text
Abstract
The biosynthetic utilization of laccase/mediator system is problematic because the use of organic cosolvent causes significant inhibition of laccase activity. This work explored how the organic cosolvent impacts on the laccase catalytic capacity towards 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in aqueous solution. Effects of acetone
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The biosynthetic utilization of laccase/mediator system is problematic because the use of organic cosolvent causes significant inhibition of laccase activity. This work explored how the organic cosolvent impacts on the laccase catalytic capacity towards 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in aqueous solution. Effects of acetone on the kinetic constants of laccase were determined and the results showed Km and Vmax varied exponentially with increasing acetone content. Acetone as well as some other cosolvents could transform ABTS radicals into its reductive form. The content of acetone in media significantly affected the radical scavenging rates. Up to 95% of the oxidized ABTS was successfully recovered in 80% (v/v) acetone in 60 min. This allows ABTS recycles at least six times with 70%–75% of active radicals recovered after each cycle. This solvent-based recovery strategy may help improve the economic feasibility of laccase/ABTS system in biosynthesis. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessArticle Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties
Molecules 2015, 20(11), 19914-19928; doi:10.3390/molecules201119661
Received: 19 August 2015 / Revised: 15 October 2015 / Accepted: 23 October 2015 / Published: 5 November 2015
Cited by 6 | PDF Full-text (3817 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A variety of novel 5-aryl thiophenes 4ag containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT)
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A variety of novel 5-aryl thiophenes 4ag containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4ag was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity ~46.23 ± 0.11 at 15 µg/mL with IC50 17.1 µg/mL. Moreover, some other compounds 4af also exhibited very good inhibition against urease enzyme. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Development and Characterization of Polymorphic Microsatellite Markers for Sedum sarmentosum (Crassulaceae) and Their Cross-Species Transferability
Molecules 2015, 20(11), 19929-19935; doi:10.3390/molecules201119669
Received: 17 August 2015 / Revised: 8 October 2015 / Accepted: 10 October 2015 / Published: 5 November 2015
Cited by 1 | PDF Full-text (191 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sedum sarmentosum is an important Chinese medicinal herb that exhibits anti-inflammatory, anti-angiogenic and anti-nociceptive properties. However, little is known about its genetic background. The first set of 14 microsatellite markers were isolated and characterized for S. sarmentosum using an SSR-enriched library. Fourteen polymorphic
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Sedum sarmentosum is an important Chinese medicinal herb that exhibits anti-inflammatory, anti-angiogenic and anti-nociceptive properties. However, little is known about its genetic background. The first set of 14 microsatellite markers were isolated and characterized for S. sarmentosum using an SSR-enriched library. Fourteen polymorphic microsatellite markers were acquired with satisfactory amplifications and a polymorphic pattern in 48 S. sarmentosum individuals. The number of alleles ranged from 3 to 15. The observed and expected heterozygosities varied from 0.0833 to 0.8750 and 0.2168 to 0.9063, respectively. Two loci showed significant departure from the Hardy-Weinberg equilibrium. Cross-species amplification was carried out in other Sedum species. High rates of cross-species amplification were observed. The transferability value ranged from 85.7% in S. lineare to 64.3% in S. ellacombianum. These markers will be valuable for studying the genetic variation, population structure and germplasm characterization of S. sarmentosum and related Sedum species. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Production of Nanoemulsions from Palm-Based Tocotrienol Rich Fraction by Microfluidization
Molecules 2015, 20(11), 19936-19946; doi:10.3390/molecules201119666
Received: 10 July 2015 / Revised: 23 August 2015 / Accepted: 25 August 2015 / Published: 5 November 2015
Cited by 3 | PDF Full-text (942 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120
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In the present study, tocotrienol rich fraction (TRF) nanoemulsions were produced as an alternative approach to improve solubility and absorption of tocotrienols. In the present study, droplet size obtained after 10 cycles of homogenization with increasing pressure was found to decrease from 120 to 65.1 nm. Nanoemulsions stabilized with Tween series alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) homogenized at 25,000 psi and 10 cycles, produced droplet size less than 100 nm and a narrow size distribution with a polydispersity index (PDI) value lower than 0.2. However blend of Tween series with Span 80 produced nanoemulsions with droplet size larger than 200 nm. This work has also demonstrated the amount of tocols losses in TRF nanoemulsion stabilized Tweens alone or emulsifier blend Brij 35:Span 80 (0.6:0.4 w/w) ranged between 3%–25%. This can be attributed to the interfacial film formed surrounding the droplets exhibited different level of oxidative stability against heat and free radicals created during high pressure emulsification. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Phenolic Compounds from the Flowers of Bombax malabaricum and Their Antioxidant and Antiviral Activities
Molecules 2015, 20(11), 19947-19957; doi:10.3390/molecules201119660
Received: 28 August 2015 / Revised: 20 October 2015 / Accepted: 27 October 2015 / Published: 5 November 2015
Cited by 3 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new phenolic compounds 13 and twenty known ones 423 were isolated from the flowers of Bombax malabaricum. Their chemical structures were elucidated by spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR) and chemical reactions. The antioxidant capacities of
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Three new phenolic compounds 13 and twenty known ones 423 were isolated from the flowers of Bombax malabaricum. Their chemical structures were elucidated by spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR) and chemical reactions. The antioxidant capacities of the isolated compounds were tested using FRAP and DPPH radical-scavenging assays, and compounds 4, 6, 8, 12, as well as the new compound 2, exhibited stronger antioxidant activities than ascorbic acid. Furthermore, all of compounds were tested for their antiviral activities against RSV by the CPE reduction assay and plaque reduction assay. Compounds 4, 10, 12 possess in vitro antiviral activities, and compound 10 exhibits potent anti-RSV effects, comparable to the positive control ribavirin. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Water-Soluble Lignins from Different Bioenergy Crops Stimulate the Early Development of Maize (Zea mays, L.)
Molecules 2015, 20(11), 19958-19970; doi:10.3390/molecules201119671
Received: 5 August 2015 / Revised: 19 October 2015 / Accepted: 23 October 2015 / Published: 5 November 2015
Cited by 4 | PDF Full-text (2273 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The molecular composition of water-soluble lignins isolated from four non-food bioenergy crops (cardoon CAR, eucalyptus EUC, and two black poplars RIP and LIM) was characterized in detail, and their potential bioactivity towards maize germination and early growth evaluated. Lignins were found to not
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The molecular composition of water-soluble lignins isolated from four non-food bioenergy crops (cardoon CAR, eucalyptus EUC, and two black poplars RIP and LIM) was characterized in detail, and their potential bioactivity towards maize germination and early growth evaluated. Lignins were found to not affect seed germination rates, but stimulated the maize seedling development, though to a different extent. RIP promoted root elongation, while CAR only stimulated the length of lateral seminal roots and coleoptile, and LIM improved only the coleoptile development. The most significant bioactivity of CAR was related to its large content of aliphatic OH groups, C-O carbons and lowest hydrophobicity, as assessed by 31P-NMR and 13C-CPMAS-NMR spectroscopies. Less bioactive RIP and LIM lignins were similar in composition, but their stimulation of maize seedling was different. This was accounted to their diverse content of aliphatic OH groups and S- and G-type molecules. The poorest bioactivity of the EUC lignin was attributed to its smallest content of aliphatic OH groups and largest hydrophobicity. Both these features may be conducive of a EUC conformational structure tight enough to prevent its alteration by organic acids exuded from vegetal tissues. Conversely the more labile conformational arrangements of the other more hydrophilic lignin extracts promoted their bioactivity by releasing biologically active molecules upon the action of exuded organic acids. Our findings indicate that water-soluble lignins from non-food crops may be effectively used as plant biostimulants, thus contributing to increase the economic and ecological liability of bio-based industries. Full article
(This article belongs to the Special Issue Biocatalytic Lignin Modification)
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Open AccessArticle Immobilization of Cyclooxygenase-2 on Silica Gel Microspheres: Optimization and Characterization
Molecules 2015, 20(11), 19971-19983; doi:10.3390/molecules201119670
Received: 4 August 2015 / Accepted: 28 August 2015 / Published: 5 November 2015
Cited by 4 | PDF Full-text (2388 KB) | HTML Full-text | XML Full-text
Abstract
In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica
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In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica gel microspheres was activated by 0.25% GA solution for 6 h and mixed with 5 U of free recombinant COX-2 solution. Then, the mixture was shaken for 8 h at 20 °C. Results showed that the immobilized COX-2 produced by this method exhibited excellent biocatalytic activity, equivalent to that of free COX-2 under the test conditions employed. The best biocatalytic activity of immobilized COX-2 appeared at pH 8.0 and still maintained at about 84% (RSD < 7.39%, n = 3) at pH 10.0. For temperature tolerance, immobilized COX-2 exhibited its maximum biocatalytic activity at 40 °C and about 68% (RSD < 6.99%, n = 3) of the activity was maintained at 60 °C. The immobilized COX-2 retained over 85% (RSD < 7.26%, n = 3) of its initial biocatalytic activity after five cycles, and after 10 days storage, the catalytic activity of immobilized COX-2 still maintained at about 95% (RSD < 3.08%, n = 3). These characteristics ensured the convenient use of the immobilized COX-2 and reduced its production cost. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Efficient Syntheses of 1,2,3-Triazoloamide Derivatives Using Solid- and Solution-Phase Synthetic Approaches
Molecules 2015, 20(11), 19984-20013; doi:10.3390/molecules201119673
Received: 16 September 2015 / Revised: 28 October 2015 / Accepted: 29 October 2015 / Published: 5 November 2015
Cited by 3 | PDF Full-text (3027 KB) | HTML Full-text | XML Full-text
Abstract
Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The
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Efficient synthetic routes for the preparation of secondary and tertiary 1,2,3-triazoloamide derivatives were developed. A secondary α-1,2,3-triazoloamide library was constructed and expanded by a previously developed solid-phase synthetic route and a tertiary 1,2,3-triazoloamide library was constructed by a parallel solution-phase synthetic route. The synthetic routes rely on amide formation with secondary amines and chloro-acid chlorides; SN2 reaction with sodium azide; and the selective [3 + 2] Hüisgen cycloaddition with appropriate terminal alkynes. The target secondary and tertiary 1,2,3-triazoloamide derivatives were obtained with three-diversity points in excellent overall yields and purities using the reported solid- and solution-phase synthetic routes, respectively. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Bitter Gentian Teas: Nutritional and Phytochemical Profiles, Polysaccharide Characterisation and Bioactivity
Molecules 2015, 20(11), 20014-20030; doi:10.3390/molecules201119674
Received: 15 October 2015 / Revised: 29 October 2015 / Accepted: 30 October 2015 / Published: 5 November 2015
Cited by 5 | PDF Full-text (1025 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally
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As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally characterized with respect to their macronutrients, demonstrating the predominance of polysaccharides and low lipid content. Gentian decoctions were also submitted to a microcolumn RP-HPLC-UV analysis of phytochemicals demonstrating a high content of iridoids (177.18–641.04 μg/mL) and flavonoids (89.15–405.71 μg/mL). Additionally, mangiferin was detected in samples of G. triflora tea (19.89 μg/mL). Five free sugars (fructose, glucose, sucrose, gentiobiose, gentianose) were identified in all gentian teas studied, as well as six organic acids (malic, citric, tartaric, oxalic, succinic, quinic). Pectic polysaccharides with a high content of rhamnogalacturonans and arabinogalactans were also identified and characterized in gentian decoctions for the first time. Gentian tea decoctions and their specific compounds (gentiopicroside, loganic acid-6′-O-β-d-glucoside, isoorientin, isoorientin-4′-O-β-d-glucoside, mangiferin, water-soluble polysaccharides) showed a promising antimicrobial, anti-inflammatory and antioxidant potentials. Evidences obtained indicate the prospective use of gentian herb teas as food products and medicines. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Pharmacokinetics of Ginkgolide B after Oral Administration of Three Different Ginkgolide B Formulations in Beagle Dogs
Molecules 2015, 20(11), 20031-20041; doi:10.3390/molecules201119678
Received: 8 September 2015 / Revised: 27 October 2015 / Accepted: 28 October 2015 / Published: 6 November 2015
Cited by 2 | PDF Full-text (1384 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a
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Ginkgolide B (GB), an important active constituent of Ginkgo biloba extract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions at m/z (Q1/Q3) 423.1/367.1 for GB and m/z 269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmax values of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Design, Synthesis and in Vivo Evaluation of Novel Glycosylated Sulfonylureas as Antihyperglycemic Agents
Molecules 2015, 20(11), 20063-20078; doi:10.3390/molecules201119676
Received: 17 September 2015 / Revised: 20 October 2015 / Accepted: 21 October 2015 / Published: 6 November 2015
PDF Full-text (1352 KB) | HTML Full-text | XML Full-text
Abstract
Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the
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Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the introduction of the glucosamine moiety is to enhance selective drug uptake by pancreatic β-cells in order to decrease the cardiotoxic side effect commonly associated with sulfonylurea agents. 2-Deoxy-2-(4-chlorophenylsulfonylurea)-d-glucopyranose was found to be the most potent antihyperglycaemic agents among the synthesized compounds in diabetic mice. This investigation indicates the importance of this novel class as potential antihyperglycaemic agents. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synergy and Other Interactions between Polymethoxyflavones from Citrus Byproducts
Molecules 2015, 20(11), 20079-20106; doi:10.3390/molecules201119677
Received: 8 October 2015 / Revised: 28 October 2015 / Accepted: 29 October 2015 / Published: 6 November 2015
Cited by 8 | PDF Full-text (3152 KB) | HTML Full-text | XML Full-text
Abstract
The citrus by-products released from citrus processing plants may contain high levels of potentially bioactive compounds such as flavonoids, which are a widely distributed group of polyphenolic compounds with health-related properties based on their antioxidant activity. In the study reported here, the potential
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The citrus by-products released from citrus processing plants may contain high levels of potentially bioactive compounds such as flavonoids, which are a widely distributed group of polyphenolic compounds with health-related properties based on their antioxidant activity. In the study reported here, the potential bioactivities and antioxidant activities of extracts, fractions and compounds from citrus by-products were evaluated along with the chemical interactions of binary mixtures of compounds and complex mixtures. The bioactivities and interactions were evaluated in wheat coleoptile bioassays and the antioxidant activity was evaluated by the al DPPH (2,2-diphenyl-1-picrylhdrazyl radical) radical scavenging assay. The extracts, fractions and most of the isolated compounds (mainly polymethoxyflavones) showed high activity in the wheat coleoptile bioassay. However, the antioxidant activity was not consistently high, except in the acetone extract fractions. Moreover, a study of the interactions with binary mixtures of polymethoxyflavones showed the occurrence of synergistic effects. The complex mixtures of fractions composed mainly of polymethoxyflavones caused a synergistic effect when it was added to a bioactive compound such as anethole. The results reported here highlight a new application for the wheat coleoptile bioassay as a quick tool to detect potential synergistic effects in compounds or mixtures. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle Extremely Randomized Machine Learning Methods for Compound Activity Prediction
Molecules 2015, 20(11), 20107-20117; doi:10.3390/molecules201119679
Received: 14 August 2015 / Revised: 14 August 2015 / Accepted: 27 October 2015 / Published: 9 November 2015
Cited by 1 | PDF Full-text (948 KB) | HTML Full-text | XML Full-text
Abstract
Speed, a relatively low requirement for computational resources and high effectiveness of the evaluation of the bioactivity of compounds have caused a rapid growth of interest in the application of machine learning methods to virtual screening tasks. However, due to the growth of
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Speed, a relatively low requirement for computational resources and high effectiveness of the evaluation of the bioactivity of compounds have caused a rapid growth of interest in the application of machine learning methods to virtual screening tasks. However, due to the growth of the amount of data also in cheminformatics and related fields, the aim of research has shifted not only towards the development of algorithms of high predictive power but also towards the simplification of previously existing methods to obtain results more quickly. In the study, we tested two approaches belonging to the group of so-called ‘extremely randomized methods’—Extreme Entropy Machine and Extremely Randomized Trees—for their ability to properly identify compounds that have activity towards particular protein targets. These methods were compared with their ‘non-extreme’ competitors, i.e., Support Vector Machine and Random Forest. The extreme approaches were not only found out to improve the efficiency of the classification of bioactive compounds, but they were also proved to be less computationally complex, requiring fewer steps to perform an optimization procedure. Full article
(This article belongs to the Special Issue Chemoinformatics)
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Open AccessArticle Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action
Molecules 2015, 20(11), 20118-20130; doi:10.3390/molecules201119680
Received: 9 September 2015 / Revised: 27 October 2015 / Accepted: 2 November 2015 / Published: 9 November 2015
Cited by 3 | PDF Full-text (2153 KB) | HTML Full-text | XML Full-text
Abstract
Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that
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Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2′-hydroxyphenyl)-4-hydroxy-methyl- 4,5-dihydrothiazole (7h) and (R)-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h′) exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs) ranging from 3.91 to 31.24 μg·mL−1. The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2′-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM) and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Molecular Differentiated Initiator Reactivity in the Synthesis of Poly(caprolactone)-Based Hydrophobic Homopolymer and Amphiphilic Core Corona Star Polymers
Molecules 2015, 20(11), 20131-20145; doi:10.3390/molecules201119681
Received: 7 October 2015 / Revised: 26 October 2015 / Accepted: 27 October 2015 / Published: 9 November 2015
Cited by 1 | PDF Full-text (3156 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Macromolecules that possess three-dimensional, branched molecular structures are of great interest because they exhibit significantly differentiated application performance compared to conventional linear (straight chain) polymers. This paper reports the synthesis of 3- and 4-arm star branched polymers via ring opening polymerisation (ROP) utilising
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Macromolecules that possess three-dimensional, branched molecular structures are of great interest because they exhibit significantly differentiated application performance compared to conventional linear (straight chain) polymers. This paper reports the synthesis of 3- and 4-arm star branched polymers via ring opening polymerisation (ROP) utilising multi-functional hydroxyl initiators and Sn(Oct)2 as precatalyst. The structures produced include mono-functional hydrophobic and multi-functional amphiphilic core corona stars. The characteristics of the synthetic process were shown to be principally dependent upon the physical/dielectric properties of the initiators used. ROP’s using initiators that were more available to become directly involved with the Sn(Oct)2 in the “in-situ” formation of the true catalytic species were observed to require shorter reaction times. Use of microwave heating (MWH) in homopolymer star synthesis reduced reaction times compared to conventional heating (CH) equivalents, this was attributed to an increased rate of “in-situ” catalyst formation. However, in amphiphilic core corona star formation, the MWH polymerisations exhibited slower propagation rates than CH equivalents. This was attributed to macro-structuring within the reaction medium, which reduced the potential for reaction. It was concluded that CH experiments were less affected by this macro-structuring because it was disrupted by the thermal currents/gradients caused by the conductive/convective heating mechanisms. These gradients are much reduced/absent with MWH because it selectively heats specific species simultaneously throughout the entire volume of the reaction medium. These partitioning problems were overcome by introducing additional quantities of the species that had been determined to selectively heat. Full article
(This article belongs to the Special Issue Microwave-Assisted Organic Synthesis)
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Open AccessArticle Membrane Disintegration Caused by the Steroid Saponin Digitonin Is Related to the Presence of Cholesterol
Molecules 2015, 20(11), 20146-20160; doi:10.3390/molecules201119682
Received: 25 June 2015 / Revised: 22 October 2015 / Accepted: 23 October 2015 / Published: 9 November 2015
Cited by 5 | PDF Full-text (40226 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the present investigation we studied the molecular mechanisms of the monodesmosidic saponin digitonin on natural and artificial membranes. We measured the hemolytic activity of digitonin on red blood cells (RBCs). Also different lipid membrane models (large unilamellar vesicles, LUVs, and giant unilamellar
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In the present investigation we studied the molecular mechanisms of the monodesmosidic saponin digitonin on natural and artificial membranes. We measured the hemolytic activity of digitonin on red blood cells (RBCs). Also different lipid membrane models (large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs) in the presence and absence of cholesterol were employed. The stability and permeability of the different vesicle systems were studied by using calcein release assay, GUVs membrane permeability assay using confocal microscopy (CM) and fluorescence correlation spectroscopy (FCS) and vesicle size measurement by dynamic light scattering (DLS). The results support the essential role of cholesterol in explaining how digitonin can disintegrate biological and artificial membranes. Digitonin induces membrane permeability or causes membrane rupturing only in the presence of cholesterol in an all-or-none mechanism. This effect depends on the concentrations of both digitonin and cholesterol. At low concentrations, digitonin induces membrane permeability while keeping the membrane intact. When digitonin is combined with other drugs, a synergistic potentiation can be observed because it facilitates their uptake. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle New Sulphated Flavonoids from Wissadula periplocifolia (L.) C. Presl (Malvaceae)
Molecules 2015, 20(11), 20161-20172; doi:10.3390/molecules201119685
Received: 18 September 2015 / Revised: 26 October 2015 / Accepted: 30 October 2015 / Published: 9 November 2015
Cited by 6 | PDF Full-text (380 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five
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Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five new sulphated flavonoids: 8-O-sulphate isoscutellarein (yannin) (1a); 4′-O-methyl-7-O-sulphate isoscutellarein (beltraonin) (1b); 7-O-sulphate acacetin (wissadulin) (2a); 4′-O-methyl-8-O-sulphate isoscutellarein (caicoine) (2b) and 3′-O-methyl-8-O-sulphate hypolaetin (pedroin) (3b) along with the known flavonoids 7,4′-di-O-methyl-8-O-sulphate isoscutellarein (4), acacetin, apigenin, isoscutellarein, 4´-O-methyl isoscutellarein, 7,4′-di-O-methylisoscutellarein, astragalin and tiliroside. The compounds were isolated by column chromatography and identified by NMR (1H, 13C, HMQC, HMBC and COSY) and LC-HRMS. A cell based assay was carried out to evaluate the preliminary cytotoxic properties of the flavonoids against UVW glioma and PC-3M prostate cancer cells as well as non-tumour cell lines. The obtained results showed that acacetin, tiliroside, a mixture of acacetin + apigenin and the sulphated flavonoids 2a + 2b exhibited inhibitory activity against at least one of the cell lines tested. Among the tested flavonoids acacetin and tiliroside showed lower IC50 values, presenting promising antitumor effects. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Glycosylated Metal Phthalocyanines
Molecules 2015, 20(11), 20173-20185; doi:10.3390/molecules201119683
Received: 11 August 2015 / Revised: 14 October 2015 / Accepted: 16 October 2015 / Published: 10 November 2015
Cited by 2 | PDF Full-text (3167 KB) | HTML Full-text | XML Full-text
Abstract
In the first part; the syntheses of mono-; di-; and tetra-glycosylated phthalonitriles is described; which are the most used starting materials for the preparation of the corresponding glycosylated metal (mostly zinc) phthalocyanines. In the second section; the preparation of symmetric and unsymmetric mono-;
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In the first part; the syntheses of mono-; di-; and tetra-glycosylated phthalonitriles is described; which are the most used starting materials for the preparation of the corresponding glycosylated metal (mostly zinc) phthalocyanines. In the second section; the preparation of symmetric and unsymmetric mono-; tetra-; and octa- glycosylated zinc phthalocyanines are reviewed; in which the sugar is attached to the phthalocyanine macrocycle; either anomerically or via another one of its OH-groups. Full article
(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)
Open AccessArticle Synthesis of Novel β-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents
Molecules 2015, 20(11), 20186-20194; doi:10.3390/molecules201119684
Received: 4 September 2015 / Revised: 30 October 2015 / Accepted: 2 November 2015 / Published: 10 November 2015
Cited by 7 | PDF Full-text (2634 KB) | HTML Full-text | XML Full-text
Abstract
Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a
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Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241) human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO). Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Isomerization of Internal Alkynes to Iridium(III) Allene Complexes via C–H Bond Activation: Expanded Substrate Scope, and Progress towards a Catalytic Methodology
Molecules 2015, 20(11), 20195-20205; doi:10.3390/molecules201119686
Received: 1 June 2015 / Revised: 29 October 2015 / Accepted: 2 November 2015 / Published: 10 November 2015
Cited by 2 | PDF Full-text (3743 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis of a series of allene complexes (POCOP)Ir(η2-RC=.=CR’) 1b4b (POCOP = 2,6-bis(di-tert-butylphosphonito)benzene) via isomerization of internal alkynes is reported. We have demonstrated that the application of this methodology is viable for the isomerization of
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The synthesis of a series of allene complexes (POCOP)Ir(η2-RC=.=CR’) 1b4b (POCOP = 2,6-bis(di-tert-butylphosphonito)benzene) via isomerization of internal alkynes is reported. We have demonstrated that the application of this methodology is viable for the isomerization of a wide variety of alkyne substrates. Deuterium labeling experiments support our proposed mechanism. The structures of the allene complexes 1b4b were determined using spectroscopic data analysis. Additionally, the solid-state molecular structure of complex 2b was determined using single crystal X-ray diffraction studies and it confirmed the assignment of an iridium-bound allene isomerization product. The rates of isomerization were measured using NMR techniques over a range of temperatures to allow determination of thermodynamic parameters. Finally, we report a preliminary step towards developing a catalytic methodology; the allene may be liberated from the metal center by exposure of the complex to an atmosphere of carbon monoxide. Full article
(This article belongs to the Special Issue C-H Bond Activation and Functionalization)
Open AccessArticle Functional Analysis of the Isopentenyl Diphosphate Isomerase of Salvia miltiorrhiza via Color Complementation and RNA Interference
Molecules 2015, 20(11), 20206-20218; doi:10.3390/molecules201119689
Received: 28 September 2015 / Revised: 2 November 2015 / Accepted: 3 November 2015 / Published: 10 November 2015
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Abstract
Isopentenyl diphosphate isomerase (IPI) catalyzes the isomerization between the common terpene precursor substances isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) during the terpenoid biosynthesis process. In this study, tissue expression analysis revealed that the expression level of the Salvia miltiorrhiza IPI1 gene (
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Isopentenyl diphosphate isomerase (IPI) catalyzes the isomerization between the common terpene precursor substances isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) during the terpenoid biosynthesis process. In this study, tissue expression analysis revealed that the expression level of the Salvia miltiorrhiza IPI1 gene (SmIPI1) was higher in the leaves than in the roots and stems. Furthermore, color complementation and RNA interference methods were used to verify the function of the SmIPI1 gene from two aspects. A recombinant SmIPI1 plasmid was successfully constructed and transferred into engineered E. coli for validating the function of SmIPI1 through the color difference in comparison to the control group; the observed color difference indicated that SmIPI1 served in promoting the accumulation of lycopene. Transformant hairy root lines with RNA interference of SmIPI1 were successfully constructed mediated by Agrobacterium rhizogenes ACCC 10060. RNA interference hairy roots had a severe phenotype characterized by withering, deformity or even death. The mRNA expression level of SmIPI1 in the RSi3 root line was only 8.4% of that of the wild type. Furthermore the tanshinone content was too low to be detected in the RNA interference lines. These results suggest that SmIPI1 plays a critical role in terpenoid metabolic pathways. Addition of an exogenous SmIPI1 gene promoted metabolic flow toward the biosynthesis of carotenoids in E. coli, and SmIPI1 interference in S. miltiorrhiza hairy roots may cause interruption of the 2-C-methyl-D-erythritol-4-phosphate metabolic pathway. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Genetic Authentication of Gardenia jasminoides Ellis var. grandiflora Nakai by Improved RAPD-Derived DNA Markers
Molecules 2015, 20(11), 20219-20229; doi:10.3390/molecules201119687
Received: 21 August 2015 / Revised: 18 October 2015 / Accepted: 3 November 2015 / Published: 10 November 2015
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Abstract
The evergreen shrub, Gardenia jasminoides Ellis var. grandiflora Nakai is one of the most popular garden-plants, with significant ornamental importance. Here, we have cloned improved random amplified polymorphic DNA (RAPD) derived fragments into T-vector, and developed sequence-characterized amplified region (SCAR) markers. These markers
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The evergreen shrub, Gardenia jasminoides Ellis var. grandiflora Nakai is one of the most popular garden-plants, with significant ornamental importance. Here, we have cloned improved random amplified polymorphic DNA (RAPD) derived fragments into T-vector, and developed sequence-characterized amplified region (SCAR) markers. These markers have been deposited in GenBank database with the accession numbers KP641310, KP641311, KP641312 and KP641313 respectively. The BLAST search of database confirmed the novelty of these markers. The four SCAR markers, namely ZZH11, ZZH31, ZZH41 and ZZH51 can specifically recognize the genetic materials of G. jasminoides from other plant species. Moreover, SCAR marker ZZH31 can be used to distinguish G. jasminoides Ellis var. grandiflora Nakai from other G. jasminoides on the market. Together, this study has developed four stably molecular SCAR markers by improved RAPD-derived DNA markers for the genetic identification and authentication, and for ecological conservation of medicinal and ornamental plant G. jasminoides. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Auraptene Acts as an Anti-Inflammatory Agent in the Mouse Brain
Molecules 2015, 20(11), 20230-20239; doi:10.3390/molecules201119691
Received: 25 September 2015 / Revised: 24 October 2015 / Accepted: 5 November 2015 / Published: 10 November 2015
Cited by 8 | PDF Full-text (5841 KB) | HTML Full-text | XML Full-text
Abstract
The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and
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The anti-inflammatory activity of auraptene (AUR), a citrus coumarin, in peripheral tissues is well-known, and we previously demonstrated that AUR exerts anti-inflammatory effects in the ischemic brain; the treatment of mice with AUR for eight days immediately after ischemic surgery suppressed demise and neuronal cell death in the hippocampus, possibly through its anti-inflammatory effects in the brain. We suggested that these effects were at least partly mediated by the suppression of inflammatory mediators derived from astrocytes. The present study showed that (1) AUR, as a pretreatment for five days before and another three days after ischemic surgery, suppressed microglial activation, cyclooxygenase (COX)-2 expression in astrocytes, and COX-2 mRNA expression in the hippocampus; (2) AUR suppressed the lipopolysaccharide-induced expression of COX-2 mRNA and the mRNA of pro-inflammatory cytokines in cultured astrocytes; (3) AUR was still detectable in the brain 60 min after its intraperitoneal administration. These results support our previous suggestion that AUR directly exerts anti-inflammatory effects on the brain. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
Open AccessArticle Role of the Red Ginseng in Defense against the Environmental Heat Stress in Sprague Dawley Rats
Molecules 2015, 20(11), 20240-20253; doi:10.3390/molecules201119692
Received: 18 September 2015 / Revised: 3 November 2015 / Accepted: 5 November 2015 / Published: 10 November 2015
Cited by 2 | PDF Full-text (2670 KB) | HTML Full-text | XML Full-text
Abstract
Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the
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Global temperature change causes heat stress related disorders in humans. A constituent of red ginseng has been known the beneficial effect on the resistance to many diseases. However, the mechanism of red ginseng (RG) against heat stress still remains unclear. To determine the effect of RG on heat stress, we examined the effect of the RG on the gene expression profiles in rats subjected to environmental heat stress. We evaluated the transcripts associated with hepatic lipid accumulation and oxidative stress in rats subjected to heat stress. We also analyzed the reactive oxygen species (ROS) contents. Our results suggested RG inhibited heat stress mediated altering mRNA expressions include HSPA1, DEAF1, HMGCR, and FMO1. We also determined RG attenuated fat accumulation in the liver by altering C/EBPβ expression. RG promoted to repress the heat stress mediated hepatic cell death by inhibiting of Bcl-2 expression in rats subjected to heat stress. Moreover, RG administered group during heat stress dramatically decreased the malondialdehyde (MDA) contents and ROS associated genes compared with the control group. Thus, we suggest that RG might influence inhibitory effect on environmental heat stress induced abnormal conditions in humans. Full article
(This article belongs to the collection Herbal Medicine Research)
Open AccessArticle Molecular Cloning, Expression Pattern and Genotypic Effects on Glucoraphanin Biosynthetic Related Genes in Chinese Kale (Brassica oleracea var. alboglabra Bailey)
Molecules 2015, 20(11), 20254-20267; doi:10.3390/molecules201119688
Received: 15 October 2015 / Revised: 29 October 2015 / Accepted: 3 November 2015 / Published: 11 November 2015
Cited by 2 | PDF Full-text (1042 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glucoraphanin is a plant secondary metabolite that is involved in plant defense and imparts health-promoting properties to cruciferous vegetables. In this study, three genes involved in glucoraphanin metabolism, branched-chain aminotransferase 4 (BCAT4), methylthioalkylmalate synthase 1 (MAM1) and dihomomethionine N-hydroxylase
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Glucoraphanin is a plant secondary metabolite that is involved in plant defense and imparts health-promoting properties to cruciferous vegetables. In this study, three genes involved in glucoraphanin metabolism, branched-chain aminotransferase 4 (BCAT4), methylthioalkylmalate synthase 1 (MAM1) and dihomomethionine N-hydroxylase (CYP79F1), were cloned from Chinese kale (Brassica oleracea var. alboglabra Bailey). Sequence homology and phylogenetic analysis identified these genes and confirmed the evolutionary status of Chinese kale. The transcript levels of BCAT4, MAM1 and CYP79F1 were higher in cotyledon, leaf and stem compared with flower and silique. BCAT4, MAM1 and CYP79F1 were expressed throughout leaf development with lower transcript levels during the younger stages. Glucoraphanin content varied extensively among different varieties, which ranged from 0.25 to 2.73 µmol·g−1 DW (dry weight). Expression levels of BCAT4 and MAM1 were high at vegetative–reproductive transition phase, while CYP79F1 was expressed high at reproductive phase. BCAT4, MAM1 and CYP79F1 were expressed significantly high in genotypes with high glucoraphanin content. All the results provided a better understanding of the roles of BCAT4, MAM1 and CYP79F1 in the glucoraphanin biosynthesis of Chinese kale. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Evaluation of the Cytotoxicity of α-Cyclodextrin Derivatives on the Caco-2 Cell Line and Human Erythrocytes
Molecules 2015, 20(11), 20269-20285; doi:10.3390/molecules201119694
Received: 5 October 2015 / Revised: 29 October 2015 / Accepted: 2 November 2015 / Published: 11 November 2015
Cited by 6 | PDF Full-text (1977 KB) | HTML Full-text | XML Full-text
Abstract
Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However,
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Cyclodextrins, even the 6-membered α-cyclodextrin, are approved in the various pharmacopoeias as pharmaceutical excipients for solubilizing and stabilizing drugs as well as for controlling drug release. Recently α-cyclodextrin has also been marketed as health food with beneficial effects on blood lipid profiles. However, the concentration of α-cyclodextrin used may be very high in these cases, and its toxic attributes have to be seriously considered. The objective of this study was to investigate the cytotoxicity of various, differently substituted α-cyclodextrin derivatives and determine relationship between the structures and cytotoxicity. Three different methods were used, viability tests (MTT assay and Real Time Cell Electronic Sensing on Caco-2 cells) as well as hemolysis test on human red blood cells. The effect of α-cyclodextrin derivatives resulted in concentration-dependent cytotoxicity, so the IC50 values have been determined. Based on our evaluation, the Real Time Cell Electronic Sensing method is the most accurate for describing the time and concentration dependency of the observed toxic effects. Regarding the cytotoxicity on Caco-2 cells, phosphatidylcholine extraction may play a main role in the mechanism. Our results should provide help in selecting those α-cyclodextrin derivatives which have the potential of being used safely in medical formulations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle β–Cyclodextrin–Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents
Molecules 2015, 20(11), 20286-20296; doi:10.3390/molecules201119696
Received: 5 September 2015 / Accepted: 7 October 2015 / Published: 12 November 2015
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Abstract
Some functionalized 1,2,4,5-tetrasubstituted imidazole derivatives were synthesized using a one-pot, four component reaction involving 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines. The synthesis has been efficiently carried out in a solvent free medium using β-cyclodextrin-propyl sulfonic acid as a catalyst to
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Some functionalized 1,2,4,5-tetrasubstituted imidazole derivatives were synthesized using a one-pot, four component reaction involving 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines. The synthesis has been efficiently carried out in a solvent free medium using β-cyclodextrin-propyl sulfonic acid as a catalyst to afford the target compounds in excellent yields. The local anesthetic effect of these derivatives was assessed in comparison to lidocaine as a standard using a rabbit corneal and mouse tail anesthesia model. The three most potent promising compounds were subjected to a rat sciatic nerve block assay where they showed considerable local anesthetic activity, along with minimal toxicity. Among the tested analogues, 4-(1-benzyl-4,5-diphenyl-1H-imidazol-2-yl)-N,N-dimethylaniline (5g) was identified as most potent analogue with minimal toxicity. It was further characterized by a more favourable therapeutic index than the standard. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Derinat Protects Skin against Ultraviolet-B (UVB)-Induced Cellular Damage
Molecules 2015, 20(11), 20297-20311; doi:10.3390/molecules201119693
Received: 12 August 2015 / Revised: 29 October 2015 / Accepted: 5 November 2015 / Published: 12 November 2015
Cited by 3 | PDF Full-text (2643 KB) | HTML Full-text | XML Full-text
Abstract
Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca2+ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases
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Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca2+ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2) expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC) channels (TRPCs), as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells
Molecules 2015, 20(11), 20312-20319; doi:10.3390/molecules201119699
Received: 25 September 2015 / Revised: 28 October 2015 / Accepted: 6 November 2015 / Published: 12 November 2015
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Abstract
A series of butylphthalide derivatives (BPDs) 18 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 18 were evaluated using a panel of human cancer cell lines. In addition,
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A series of butylphthalide derivatives (BPDs) 18 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 18 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Enhancement of Palmarumycin C12 and C13 Production by the Endophytic Fungus Berkleasmium sp. Dzf12 in an Aqueous-Organic Solvent System
Molecules 2015, 20(11), 20320-20333; doi:10.3390/molecules201119700
Received: 6 September 2015 / Revised: 4 November 2015 / Accepted: 5 November 2015 / Published: 12 November 2015
PDF Full-text (1748 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The endophytic fungus Berkleasmium sp. Dzf12, isolated from Dioscorea zingiberensis, was found to produce palmarumycins C12 and C13 which possess a great variety of biological activities. Seven biocompatible water-immiscible organic solvents including n-dodecane, n-hexadecane, 1-hexadecene, liquid paraffin, dibutyl
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The endophytic fungus Berkleasmium sp. Dzf12, isolated from Dioscorea zingiberensis, was found to produce palmarumycins C12 and C13 which possess a great variety of biological activities. Seven biocompatible water-immiscible organic solvents including n-dodecane, n-hexadecane, 1-hexadecene, liquid paraffin, dibutyl phthalate, butyl oleate and oleic acid were evaluated to improve palmarumycins C12 and C13 production in suspension culture of Berkleasmium sp. Dzf12. Among the chosen solvents both butyl oleate and liquid paraffin were the most effective to improve palmarumycins C12 and C13 production. The addition of dibutyl phthalate, butyl oleate and oleic acid to the cultures of Berkleasmium sp. Dzf12 significantly enhanced palmarumycin C12 production by adsorbing palmarumycin C12 into the organic phase. When butyl oleate was fed at 5% (v/v) in medium at the beginning of fermentation (day 0), the highest palmarumycin C12 yield (191.6 mg/L) was achieved, about a 34.87-fold increase in comparison with the control (5.3 mg/L). n-Dodecane, 1-hexadecene and liquid paraffin had a great influence on the production of palmarumycin C13. When liquid paraffin was added at 10% (v/v) in medium on day 3 of fermentation, the palmarumycin C13 yield reached a maximum value (134.1 mg/L), which was 4.35-fold that of the control (30.8 mg/L). Application of the aqueous-organic solvent system should be a simple and efficient process strategy for enhancing palmarumycin C12 and C13 production in liquid cultures of the endophytic fungus Berkleasmium sp. Dzf12. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Triterpenoids from the Herbs of Salicornia bigelovii
Molecules 2015, 20(11), 20334-20340; doi:10.3390/molecules201119695
Received: 16 September 2015 / Revised: 4 November 2015 / Accepted: 5 November 2015 / Published: 12 November 2015
Cited by 1 | PDF Full-text (639 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new nortriterpene saponin, 3-O-β-d-glucuronopyranosyl-30-norolean-12,20(29)-dien-23- oxo-28-oic acid, namely bigelovii D (11), was isolated from the hydroalcoholic extract of herbs of Salicornia bigelovii along with 10 known saponins (110). Their chemical structures were identified on the
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A new nortriterpene saponin, 3-O-β-d-glucuronopyranosyl-30-norolean-12,20(29)-dien-23- oxo-28-oic acid, namely bigelovii D (11), was isolated from the hydroalcoholic extract of herbs of Salicornia bigelovii along with 10 known saponins (110). Their chemical structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and a comparison with literature data. Some of these compounds showed potent antifungal activities in vitro. Compounds 3, 4, 5, 6, 7, 10 and 11 demonstrated potent inhibitory activities against Colletotrichum gloeosporioides and compound 11 displayed broad-spectrum inhibitory activity against Alternaria alternata, A. solani, Botrytis cinerea, C. gloeosporioides, Fusarium graminearum, F. verticilloides, Thanatephorus cucumeris and Sclerotinia sclerotiorum, with EC50 values ranging from 13.6 to 36.3 μg/mL. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Direct Aminolysis of Ethoxycarbonylmethyl 1,4-Dihydropyridine-3-carboxylates
Molecules 2015, 20(11), 20341-20354; doi:10.3390/molecules201119697
Received: 24 September 2015 / Revised: 22 October 2015 / Accepted: 27 October 2015 / Published: 12 November 2015
Cited by 1 | PDF Full-text (1839 KB) | HTML Full-text | XML Full-text
Abstract
The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines
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The ethoxycarbonylmethyl esters of 1,4-dihydropyridines were directly converted into carbamoylmethyl esters in the presence of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) in good to excellent yields under mild conditions. The use of TBD is crucial for the successful aminolysis of ethoxycarbonylmethyl ester of 1,4-dihydropyridines with secondary amines as without it the reaction does not proceed at all. The aminolysis reaction proceeded regioselectively, as the alkyl ester conjugated with the 1,4-dihydropyridine cycle was not involved in the reaction. Screening of other N-containing bases, such as triethylamine (TEA), pyridine, 4-(N,N-dimethylamino)pyridine (DMAP), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), imidazole, tetramethyl guanidine (TMG) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) as catalysts revealed no activity in the studied reaction. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Nonprenylated Xanthones from Gentiana lutea, Frasera caroliniensis, and Centaurium erythraea as Novel Inhibitors of Vascular Smooth Muscle Cell Proliferation
Molecules 2015, 20(11), 20381-20390; doi:10.3390/molecules201119703
Received: 30 September 2015 / Revised: 23 October 2015 / Accepted: 3 November 2015 / Published: 13 November 2015
Cited by 4 | PDF Full-text (2530 KB) | HTML Full-text | XML Full-text
Abstract
Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of
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Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of novel VSMC proliferation inhibitors. A natural product screening approach using a resazurin conversion assay enabled the identification of gentisin (1) from Gentiana lutea as a novel inhibitor of VSMC proliferation with an IC50 value of 7.84 µM. Aiming to identify further anti-proliferative compounds, 13 additional nonprenylated xanthones, isolated from different plant species, were also tested. While some compounds showed no or moderate activity at 30 µM, 1-hydroxy-2,3,4,5-tetramethoxyxanthone (4), swerchirin (6), and methylswertianin (7) showed IC50 values between 10.2 and 12.5 µM. The anti-proliferative effect of 1, 4, 6, and 7 was confirmed by the quantification of DNA synthesis (BrdU incorporation) in VSMC. Cell death quantification (determined by LDH release in the culture medium) revealed that the compounds are not cytotoxic in the investigated concentration range. In conclusion, nonprenylated xanthones are identified as novel, non-toxic VSMC proliferation inhibitors, which might contribute to the development of new therapeutic applications to combat restenosis. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessCommunication Temporal Variation of Aristolochia chilensis Aristolochic Acids during Spring
Molecules 2015, 20(11), 20391-20396; doi:10.3390/molecules201119704
Received: 7 October 2015 / Revised: 4 November 2015 / Accepted: 9 November 2015 / Published: 13 November 2015
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Abstract
In this communication, we report the springtime variation of the composition of aristolochic acids (AAs) in Aristolochia chilensis leaves and stems. The dominant AA in the leaves of all samples, which were collected between October and December, was AA-I (1), and
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In this communication, we report the springtime variation of the composition of aristolochic acids (AAs) in Aristolochia chilensis leaves and stems. The dominant AA in the leaves of all samples, which were collected between October and December, was AA-I (1), and its concentration varied between 212.6 ± 3.8 and 145.6 ± 1.2 mg/kg and decreased linearly. This decrease occurred in parallel with the increase in AA-Ia (5) concentration from 15.9 ± 0.8 mg/kg at the beginning of October to 96.8 ± 7.8 mg/kg in mid-December. Both acids are enzymatically related by methylation-demethylation reactions. Other AAs also showed important variations: AA-II (2) significantly increased in concentration, reaching a maximum in the first two weeks of November and subsequently decreasing in mid-December to approximately the October levels. The principal component in the AA mixture of the stems was also AA-I (1); similar to AA-II (2), its concentration increased beginning in October, peaked in the second week of November and subsequently decreased. The concentrations of AA-IIIa (6) and AA-IVa (7) in the leaves and stems varied throughout the study period, but no clear pattern was identified. Based on the variation of AAs in A. chilensis leaves and stems during the study period, the reduced contents of non-phenolic AAs and increased concentrations of phenolic AAs are likely associated with a decrease in this plant’s toxicity during the spring. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Sensitive and Rapid UHPLC-MS/MS for the Analysis of Tomato Phenolics in Human Biological Samples
Molecules 2015, 20(11), 20409-20425; doi:10.3390/molecules201119702
Received: 18 August 2015 / Revised: 19 October 2015 / Accepted: 4 November 2015 / Published: 16 November 2015
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Abstract
An UHPLC-MS/MS method for the quantification of tomato phenolic metabolites in human fluids was optimized and validated, and then applied in a pilot dietary intervention study with healthy volunteers. A 5-fold gain in speed (3.5 min of total run); 7-fold increase in MS
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An UHPLC-MS/MS method for the quantification of tomato phenolic metabolites in human fluids was optimized and validated, and then applied in a pilot dietary intervention study with healthy volunteers. A 5-fold gain in speed (3.5 min of total run); 7-fold increase in MS sensitivity and 2-fold greater efficiency (50% peak width reduction) were observed when comparing the proposed method with the reference-quality HPLC-MS/MS system, whose assay performance has been previously documented. The UHPLC-MS/MS method led to an overall improvement in the limits of detection (LOD) and quantification (LOQ) for all the phenolic compounds studied. The recoveries ranged between 68% and 100% in urine and 61% and 100% in plasma. The accuracy; intra- and interday precision; and stability met with the acceptance criteria of the AOAC International norms. Due to the improvements in the analytical method; the total phenolic metabolites detected in plasma and urine in the pilot intervention study were 3 times higher than those detected by HPLC-MS/MS. Comparing with traditional methods; which require longer time of analysis; the methodology described is suitable for the analysis of phenolic compounds in a large number of plasma and urine samples in a reduced time frame. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Essential Oil Composition, Antioxidant, Cytotoxic and Antiviral Activities of Teucrium pseudochamaepitys Growing Spontaneously in Tunisia
Molecules 2015, 20(11), 20426-20433; doi:10.3390/molecules201119707
Received: 21 September 2015 / Revised: 2 November 2015 / Accepted: 3 November 2015 / Published: 16 November 2015
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Abstract
The chemical composition, antioxidant, cytotoxic and antiviral activities of the essential oil obtained by hydrodistillation from the aerial parts of Teucrium pseudochamaepitys (Lamiaceae) collected from Zaghouan province of Tunisia are reported. The essential oil was analyzed by gas chromatography equipped with a flame
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The chemical composition, antioxidant, cytotoxic and antiviral activities of the essential oil obtained by hydrodistillation from the aerial parts of Teucrium pseudochamaepitys (Lamiaceae) collected from Zaghouan province of Tunisia are reported. The essential oil was analyzed by gas chromatography equipped with a flame ionization detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC/MS). Thirty-one compounds were identified representing 88.6% of the total essential oil. Hexadecanoic acid was found to be the most abundant component (26.1%) followed by caryophyllene oxide (6.3%), myristicin (4.9%) and α-cubebene (3.9%). The antioxidant capacity of the oil was measured on the basis of the scavenging activity to the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC50 value of the oil was evaluated as 0.77 mg·mL−1. In addition, the essential oil was found to possess moderate cytotoxic effects on the HEp-2 cell line (50% cytotoxic concentration (CC50) = 653.6 µg·mL−1). The potential antiviral effect was tested against Coxsackievirus B (CV-B), a significant human and mouse pathogen that causes pediatric central nervous system disease, commonly with acute syndromes. The reduction of viral infectivity by the essential oil was measured using a cytopathic (CPE) reduction assay. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessArticle Synthesis and Antimicrobial Evaluation of a New Series of Heterocyclic Systems Bearing a Benzosuberone Scaffold
Molecules 2015, 20(11), 20434-20447; doi:10.3390/molecules201119701
Received: 11 September 2015 / Revised: 30 October 2015 / Accepted: 4 November 2015 / Published: 16 November 2015
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Abstract
A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to
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A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives 1a,b as starting materials. Treatment of 1a,b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to afford the thioamides 4a,b, which was reacted with methyl iodide to obtain methylated products 5a,b. Cyclocondensation of 4a,b with chloroacetone 6 and phenacyl chloride 7 gave the corresponding thiophene derivatives 9ac. Reaction of 4a,b with C-acetyl-N- arylhydrazonoyl chlorides 14a and 14b in boiling EtOH in the presence of triethylamine, afforded the corresponding 1,3,4-thiadiazoline derivatives 16ad. The thioamides 4a,b were reacted with C-ethoxycarbonyl-N-arylhydrazonoyl chlorides 18a,b which afforded 1,3,4-thiadiazoline derivatives 19ad. The benzosuberones 1a,b were treated with 3-mercaptopropanoic acid to give compounds 21a,b, which were cyclized to tricyclic thiopyran-4(5H)-one derivatives 22a,b. The latter compounds 22a,b were reacted with 3-mercaptopropanoic acid to give compounds 23a,b, which were cyclized tetracyclic ring systems 24a,b. Finally, compounds 24a,b were oxidized using hydrogen peroxide under reflux conditions to afford the oxidized form of the novel tetracyclic heterogeneous ring systems 25a,b. The newly synthesized compounds were screened for antimicrobial activities. The structures of new compounds were characterized by 1H-NMR, 13C-NMR, IR, and EI-MS. Full article
(This article belongs to the collection Heterocyclic Compounds)
Open AccessArticle Optimization of Ultrasound-Assisted Extraction of Natural Antioxidants from Sugar Apple (Annona squamosa L.) Peel Using Response Surface Methodology
Molecules 2015, 20(11), 20448-20459; doi:10.3390/molecules201119708
Received: 30 September 2015 / Revised: 4 November 2015 / Accepted: 9 November 2015 / Published: 17 November 2015
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Abstract
Sugar apple (Annona squamosa L.) is a popular tropical fruit and its peel is a municipal waste. An ultrasound-assisted extraction method was developed for the recovery of natural antioxidants from sugar apple peel. Central composite design was used to optimize solvent concentration
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Sugar apple (Annona squamosa L.) is a popular tropical fruit and its peel is a municipal waste. An ultrasound-assisted extraction method was developed for the recovery of natural antioxidants from sugar apple peel. Central composite design was used to optimize solvent concentration (13.2%–46.8%), ultrasonic time (33.2–66.8 min), and temperature (43.2–76.8 °C) for the recovery of natural antioxidants from sugar apple peel. The second-order polynomial models demonstrated a good fit of the quadratic models with the experimental results in respect to total phenolic content (TPC, R2 = 0.9524, p < 0.0001), FRAP (R2 = 0.9743, p < 0.0001), and TEAC (R2 = 0.9610, p < 0.0001) values. The optimal extraction conditions were 20:1 (mL/g) of solvent-to-solid ratio, 32.68% acetone, and 67.23 °C for 42.54 min under ultrasonic irradiation. Under these conditions, the maximal yield of total phenolic content was 26.81 (mg GA/g FW). The experimental results obtained under optimal conditions agreed well with the predicted results. The application of ultrasound markedly decreased extraction time and improved the extraction efficiency, compared with the conventional methods. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Variation in Phenolics, Flavanoids, Antioxidant and Tyrosinase Inhibitory Activity of Peach Blossoms at Different Developmental Stages
Molecules 2015, 20(11), 20460-20472; doi:10.3390/molecules201119709
Received: 30 September 2015 / Revised: 2 November 2015 / Accepted: 9 November 2015 / Published: 18 November 2015
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Abstract
Peach blossoms were harvested and classified into six developmental stages: (I) bud emerging stage; (II) middle bud stage; (III) large bud stage; (IV) initial-flowering stage; (V) full-flowering stage; and (VI) end-flowering stage. The contents of total phenolics, flavanoids, individual phenolic compounds as well
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Peach blossoms were harvested and classified into six developmental stages: (I) bud emerging stage; (II) middle bud stage; (III) large bud stage; (IV) initial-flowering stage; (V) full-flowering stage; and (VI) end-flowering stage. The contents of total phenolics, flavanoids, individual phenolic compounds as well as antioxidant and tyrosinase inhibitory activity of peach blossoms at different developmental stages were investigated. The total phenolic contents varied from 149.80 to 74.80 mg chlorogenic acid equivalents/g dry weight (DW), and the total flavanoid contents ranged from 93.03 to 44.06 mg rutin equivalents/g DW. Both the contents of total phenolics and flavanoids decreased during blossom development. Chlorogenic acid was the predominant component, accounting for 62.08%–71.09% of the total amount of identified phenolic compounds in peach blossom. The antioxidant capacities determined by different assays and tyrosinase inhibitory activity also showed descending patterns during blossom development. Significant correlations were observed between antioxidant capacities with contents of total phenolics and total flavanoids as well as chlorogenic acid, cinnamic acid and kaempferol-3-O-galactoside, while the tyrosinase inhibitory activity had lower correlations with total phenolics and total flavanoids as well as chlorogenic acid, quercetin-3-O-rhamnoside, kaempferol-3-O-galactoside and cinnamic acid. The antioxidant activities of peach blossom seemed to be more dependent on the phenolic compounds than tyrosinase inhibitory activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Composition and in-Vitro Evaluation of the Antimicrobial and Antioxidant Activities of Essential Oils Extracted from Seven Eucalyptus Species
Molecules 2015, 20(11), 20487-20498; doi:10.3390/molecules201119706
Received: 27 July 2015 / Revised: 26 October 2015 / Accepted: 29 October 2015 / Published: 18 November 2015
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Abstract
Eucalyptus is well reputed for its use as medicinal plant around the globe. The present study was planned to evaluate chemical composition, antimicrobial and antioxidant activity of the essential oils (EOs) extracted from seven Eucalyptus species frequently found in South East Asia (Pakistan).
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Eucalyptus is well reputed for its use as medicinal plant around the globe. The present study was planned to evaluate chemical composition, antimicrobial and antioxidant activity of the essential oils (EOs) extracted from seven Eucalyptus species frequently found in South East Asia (Pakistan). EOs from Eucalyptus citriodora, Eucalyptus melanophloia, Eucalyptus crebra, Eucalyptus tereticornis, Eucalyptus globulus, Eucalyptus camaldulensis and Eucalyptus microtheca were extracted from leaves through hydrodistillation. The chemical composition of the EOs was determined through GC-MS-FID analysis. The study revealed presence of 31 compounds in E. citriodora and E. melanophloia, 27 compounds in E. crebra, 24 compounds in E. tereticornis, 10 compounds in E. globulus, 13 compounds in E. camaldulensis and 12 compounds in E. microtheca. 1,8-Cineole (56.5%), α-pinene (31.4%), citrinyl acetate (13.3%), eugenol (11.8%) and terpenene-4-ol (10.2%) were the highest principal components in these EOs. E. citriodora exhibited the highest antimicrobial activity against the five microbial species tested (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Aspergillus niger and Rhizopus solani). Gram positive bacteria were found more sensitive than Gram negative bacteria to all EOs. The diphenyl-1-picrylhydazyl (DPPH) radical scavenging activity and percentage inhibition of linoleic acid oxidation were highest in E. citriodora (82.1% and 83.8%, respectively) followed by E. camaldulensis (81.9% and 83.3%, respectively). The great variation in chemical composition of EOs from Eucalyptus, highlight its potential for medicinal and nutraceutical applications. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Analysis of the Constituents in “Zhu She Yong Xue Shuan Tong” by Ultra High Performance Liquid Chromatography with Quadrupole Time-of-Flight Mass Spectrometry Combined with Preparative High Performance Liquid Chromatography
Molecules 2015, 20(11), 20518-20537; doi:10.3390/molecules201119712
Received: 5 September 2015 / Revised: 27 October 2015 / Accepted: 6 November 2015 / Published: 18 November 2015
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Abstract
“Zhu She Yong Xue Shuan Tong” lyophilized powder (ZSYXST), consists of a series of saponins extracted from Panax notoginseng, which has been widely used in China for the treatment of strokes. In this study, an ultra-high performance liquid chromatography with quadrupole time-of-flight
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“Zhu She Yong Xue Shuan Tong” lyophilized powder (ZSYXST), consists of a series of saponins extracted from Panax notoginseng, which has been widely used in China for the treatment of strokes. In this study, an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) combined with preparative high performance liquid chromatography (PHPLC) method was developed to rapidly identify both major and minor saponins in ZSYXST. Some high content components were removed through PHPLC in order to increase the sensitivity of the trace saponins. Then, specific characteristic fragment ions in both positive and negative mode were utilized to determine the types of aglycone, saccharide, as well as the saccharide chain linkages. As a result, 94 saponins, including 20 pairs of isomers and ten new compounds, which could represent higher than 98% components in ZSYXST, were identified or tentatively identified in commercial ZSYXST samples. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Phenolic Profile and Comparison of Antioxidant Activities
Molecules 2015, 20(11), 20538-20550; doi:10.3390/molecules201119715
Received: 29 September 2015 / Revised: 4 November 2015 / Accepted: 4 November 2015 / Published: 18 November 2015
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Abstract
Reactive oxygen species (ROS) are highly considered in the ethiopathogenesis of different pathological conditions because they may cause significant damage to cells and tissues. In this paper, we focused on potential antioxidant properties of two medical plants such as the Agrimonia eupatoria L.
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Reactive oxygen species (ROS) are highly considered in the ethiopathogenesis of different pathological conditions because they may cause significant damage to cells and tissues. In this paper, we focused on potential antioxidant properties of two medical plants such as the Agrimonia eupatoria L. and Cynara cardunculus L. Both plants have previously been studied for their pharmacological activities, especially as hepatoprotective and hypoglycemic activities. It has been suggested, that their effects are related to the antioxidant properties of polyphenols, which are dominant compounds of the plants’ extracts. In the present study HPLC-MS analysis of water infusion was performed allowing the identification of several phenolic constituents. Furthermore, antioxidant effects of the two extracts were compared showing higher effects for agrimony extract compared to artichoke. Thus, agrimony was selected for the in vivo study using the skin flap viability model. In conclusion, our results provide evidence that the A. eupatoria extract may be a valuable source of polyphenols to be studied for the future development of supplements useful in the prevention of diseases linked to oxidative stress. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Ardipusilloside-I Metabolites from Human Intestinal Bacteria and Their Antitumor Activity
Molecules 2015, 20(11), 20569-20581; doi:10.3390/molecules201119719
Received: 29 September 2015 / Revised: 7 November 2015 / Accepted: 9 November 2015 / Published: 19 November 2015
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Abstract
Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Ardisia pusilla DC, and has been demonstrated to have potent antitumor activity. However, ADS-I metabolism in humans has not been investigated. In this study, we studied the biotransformation of ADS-I in human intestinal bacteria, and
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Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Ardisia pusilla DC, and has been demonstrated to have potent antitumor activity. However, ADS-I metabolism in humans has not been investigated. In this study, we studied the biotransformation of ADS-I in human intestinal bacteria, and examined the in vitro antitumor activity of the major metabolites. Ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) was used to detect ADS-I biotransformation products, and their chemical structures were identified by high performance liquid chromatography–nuclear magnetic resonance (HPLC–NMR). The antitumor activity of the major metabolites was determined by the MTT assay. Here, we show that main reaction seen in the metabolism of ADS-I in human intestinal bacteria was deglycosylation, which produced a total of four metabolites. The structures of the two major metabolites M1 and M2 were confirmed by using NMR. MTT assay showed that ADS-I metabolites M1 and M2 have the same levels of inhibitory activities as ADS-I in cultured SMMC-7721 cells and MCF-7 cells. In conclusion, this study demonstrates deglycosylation as a primary pathway of ADS-I metabolism in human intestinal bacteria, and suggests that the pharmacological activity of ADS-I may be mediated, at least in part, by its metabolites. Full article
(This article belongs to the Special Issue New Technologies for the Recovery of Natural Products)
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Open AccessArticle New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies
Molecules 2015, 20(11), 20642-20658; doi:10.3390/molecules201119710
Received: 21 October 2015 / Revised: 7 November 2015 / Accepted: 11 November 2015 / Published: 19 November 2015
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Abstract
The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized
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The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Cyclovirobuxine D Inhibits Cell Proliferation and Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer Cells
Molecules 2015, 20(11), 20659-20668; doi:10.3390/molecules201119729
Received: 17 August 2015 / Revised: 12 November 2015 / Accepted: 13 November 2015 / Published: 19 November 2015
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Abstract
Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects
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Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects of CVB-D on gastric cancer cells and the underlying mechanisms of action. CVB-D reduced cell viability and colony formation ability of MGC-803 and MKN28 cells in a time- and concentration-dependent manner. Flow cytometry showed that cell cycle of CVB-D treated cells was arrested at the S-phase. CVB-D also induced apoptosis in MGC-803 and MKN28 cells, especially early stage apoptosis. Furthermore, mitochondria membrane potential (Δψm) was reduced and apoptosis-related proteins, cleaved Caspase-3 and Bax/Bcl-2, were up-regulated in CVB-D-treated MGC-803 and MKN28 cells. Taken together, our studies found that CVB-D plays important roles in inhibition of gastric tumorigenesis via arresting cell cycle and inducing mitochondria-mediated apoptosis, suggesting the potential application of CVB-D in gastric cancer therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Solvatochromic and Single Crystal Studies of Two Neutral Triarylmethane Dyes with a Quinone Methide Structure
Molecules 2015, 20(11), 20688-20698; doi:10.3390/molecules201119724
Received: 7 September 2015 / Revised: 30 October 2015 / Accepted: 10 November 2015 / Published: 19 November 2015
Cited by 1 | PDF Full-text (2782 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The crystal structure of two neutral triarylmethane dyes with a p-quinone methide core was determined by X-ray diffraction analysis. The spectroscopic characteristics of both compounds in 23 solvents with different polarities or hydrogen-bonding donor (HBD) abilities has been studied as a function of
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The crystal structure of two neutral triarylmethane dyes with a p-quinone methide core was determined by X-ray diffraction analysis. The spectroscopic characteristics of both compounds in 23 solvents with different polarities or hydrogen-bonding donor (HBD) abilities has been studied as a function of three solvatochromic parameters (ET(30), π* and α). Both compounds 1 and 2 showed a pronounced bathochromic shift of the main absorption band on increasing solvent polarity and HBD ability. The correlation is better for compound 2 than for compound 1. The stronger effect and better correlation was observed for compound 2 with the increment of the solvent HBD ability (α parameter). Full article
(This article belongs to the Special Issue Photoactive Molecules)
Open AccessArticle Cinidium officinale and its Bioactive Compound, Butylidenephthalide, Inhibit Laser-Induced Choroidal Neovascularization in a Rat Model
Molecules 2015, 20(11), 20699-20708; doi:10.3390/molecules201119728
Received: 1 October 2015 / Revised: 13 November 2015 / Accepted: 16 November 2015 / Published: 19 November 2015
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Abstract
Choroidal neovascularization (CNV) is a common pathology in age-related macular degeneration. In this study, we evaluated in a rat model the effect of an extract of Cinidium officinale Makino and its bioactive compound, butylidenephthalide, on laser-induced CNV. Experimental CNV was induced in Long-Evans
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Choroidal neovascularization (CNV) is a common pathology in age-related macular degeneration. In this study, we evaluated in a rat model the effect of an extract of Cinidium officinale Makino and its bioactive compound, butylidenephthalide, on laser-induced CNV. Experimental CNV was induced in Long-Evans rats by laser photocoagulation. C. officinale extract (COE) and butylidenephthalide was intraperitoneally injected once per day for ten days after laser photocoagulation. Choroidal flat mounts were prepared to measure CNV areas and macrophage infiltration. We used a protein array to evaluate the expression levels of angiogenic factors. The CNV area and macrophage infiltration in COE-treated rats were significantly lower than in vehicle-treated rats. COE decreased the expression levels of IGFBP-1, MCP-1, PAI-1, and VEGF. Additionally, butylidenephthalide also inhibited the laser-induced CNV formation and macrophage infiltration and down-regulated the expression of IGFBP-1, MCP-1 and VEGF. These results suggest that COE exerts anti-angiogenic effects on laser-induced CNV by inhibiting the expression of IGFBP-1, MCP-1, and VEGF, indicating that anti-angiogenic activities of COE may be in part due to its bioactive compound, butylidenephthalide. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication An Efficient and Recyclable Nanoparticle-Supported Cobalt Catalyst for Quinoxaline Synthesis
Molecules 2015, 20(11), 20709-20718; doi:10.3390/molecules201119731
Received: 23 September 2015 / Revised: 3 November 2015 / Accepted: 12 November 2015 / Published: 19 November 2015
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Abstract
The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The supported nanocatalyst exhibited excellent activity and stability and it could be reused for at least ten times without any loss
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The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The supported nanocatalyst exhibited excellent activity and stability and it could be reused for at least ten times without any loss of activity. No cobalt contamination could be detected in the products by AAS measurements, pointing to the excellent activity and stability of the Co nanomaterial. Full article
(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)
Open AccessArticle Condensation of Diacetyl with Alkyl Amines: Synthesis and Reactivity of p-Iminobenzoquinones and p-Diiminobenzoquinones
Molecules 2015, 20(11), 20719-20740; doi:10.3390/molecules201119716
Received: 16 October 2015 / Revised: 5 November 2015 / Accepted: 6 November 2015 / Published: 20 November 2015
PDF Full-text (2052 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Condensation reactions between diacetyl and α-branched primary alkylamines under mild and neutral conditions provided a mixture of 2,5-dimethylbenzoquinone(alkylimines), 2,5-dimethylbenzoquinone(bis-alkyldiimines), and N,N′-dialkyl-2,5-dimethylbenzene-1,4-diamines, which were efficiently separated as pure products by column chromatography. Both 2,5-dimethylbenzoquinone(alkylimines) and 2,5-dimethylbenzoquinone(bis-alkyldiimines) underwent
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Condensation reactions between diacetyl and α-branched primary alkylamines under mild and neutral conditions provided a mixture of 2,5-dimethylbenzoquinone(alkylimines), 2,5-dimethylbenzoquinone(bis-alkyldiimines), and N,N′-dialkyl-2,5-dimethylbenzene-1,4-diamines, which were efficiently separated as pure products by column chromatography. Both 2,5-dimethylbenzoquinone(alkylimines) and 2,5-dimethylbenzoquinone(bis-alkyldiimines) underwent an interchange of the alkylimino group when treated with anilines, followed by reductive aromatization, to provide diarylamines and 1,4-dianilinobenzenes, respectively. Evaluation was also made of the reactivity and selectivity of these compounds in the presence of anilines, thiophenols and alkylhalides. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle A 7-Deazaadenosylaziridine Cofactor for Sequence-Specific Labeling of DNA by the DNA Cytosine-C5 Methyltransferase M.HhaI
Molecules 2015, 20(11), 20805-20822; doi:10.3390/molecules201119723
Received: 6 August 2015 / Revised: 3 November 2015 / Accepted: 10 November 2015 / Published: 23 November 2015
Cited by 3 | PDF Full-text (3630 KB) | HTML Full-text | XML Full-text
Abstract
DNA methyltransferases (MTases) catalyze the transfer of the activated methyl group of the cofactor S-adenosyl-l-methionine (AdoMet or SAM) to the exocyclic amino groups of adenine or cytosine or the C5 ring atom of cytosine within specific DNA sequences. The DNA adenine-N6 MTase
[...] Read more.
DNA methyltransferases (MTases) catalyze the transfer of the activated methyl group of the cofactor S-adenosyl-l-methionine (AdoMet or SAM) to the exocyclic amino groups of adenine or cytosine or the C5 ring atom of cytosine within specific DNA sequences. The DNA adenine-N6 MTase from Thermus aquaticus (M.TaqI) is also capable of coupling synthetic N-adenosylaziridine cofactor analogues to its target adenine within the double-stranded 5′-TCGA-3′ sequence. This M.TaqI-mediated coupling reaction was exploited to sequence-specifically deliver fluorophores and biotin to DNA using N-adenosylaziridine derivatives carrying reporter groups at the 8-position of the adenine ring. However, these 8-modified aziridine cofactors were poor substrates for the DNA cytosine-C5 MTase from Haemophilus haemolyticus (M.HhaI). Based on the crystal structure of M.HhaI in complex with a duplex oligodeoxynucleotide and the cofactor product, we synthesized a stable 7-deazaadenosylaziridine derivative with a biotin group attached to the 7-position via a flexible linker. This 7-modified aziridine cofactor can be efficiently used by M.HhaI for the direct, quantitative and sequence-specific delivery of biotin to the second cytosine within 5′-GCGC-3′ sequences in short duplex oligodeoxynucleotides and plasmid DNA. In addition, we demonstrate that biotinylation by M.HhaI depends on the methylation status of the target cytosine and, thus, could provide a method for cytosine-C5 DNA methylation detection in mammalian DNA. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessCommunication Two New Cyototoxic Cardenolides from the Whole Plants of Adonis multiflora Nishikawa & Koki Ito
Molecules 2015, 20(11), 20823-20831; doi:10.3390/molecules201119722
Received: 4 September 2015 / Revised: 11 November 2015 / Accepted: 13 November 2015 / Published: 23 November 2015
PDF Full-text (567 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides—adonioside A (1) and adonioside B (6)—as well as four known cardenolides: tupichinolide (2)
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A phytochemical investigation of the whole plants of Adonis multiflora Nishikawa & Koki Ito. resulted in the isolation and identification of two new cardenolides—adonioside A (1) and adonioside B (6)—as well as four known cardenolides: tupichinolide (2) oleandrine (3), cryptostigmin II (4), and cymarin (5). Their structures were elucidated on the basis of NMR, MS, and IR spectroscopic analyses. Compounds 1, 2, 5, and 6 showed significant cytotoxicity against six human cancer cell lines (HCT-116, HepG2, HeLa, SK-OV-3, and SK-MEL-5, and SK-BR-3). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Identification of RNA Oligonucleotides Binding to Several Proteins from Potential G-Quadruplex Forming Regions in Transcribed Pre-mRNA
Molecules 2015, 20(11), 20832-20840; doi:10.3390/molecules201119733
Received: 15 September 2015 / Revised: 6 November 2015 / Accepted: 12 November 2015 / Published: 23 November 2015
Cited by 1 | PDF Full-text (2165 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
G-quadruplexes (G4s) are noncanonical DNA/RNA structures formed by guanine-rich sequences. Recently, G4s have been found not only in aptamers but also in the genomic DNA and transcribed RNA. In this study, we identified new RNA oligonucleotides working as aptamers by focusing on G4-forming
[...] Read more.
G-quadruplexes (G4s) are noncanonical DNA/RNA structures formed by guanine-rich sequences. Recently, G4s have been found not only in aptamers but also in the genomic DNA and transcribed RNA. In this study, we identified new RNA oligonucleotides working as aptamers by focusing on G4-forming RNAs located within the pre-mRNA. We showed that the G4 in the 5′ UTR and first intron of VEGFA bound to the protein encoded in VEGFA gene, VEGF165, with high affinity. Moreover, G4-forming RNAs located within the PDGFA and the PDGFB introns bound to PDGF-AA and PDGF-BB, respectively, indicating that G4 in the pre-mRNA could be an aptamer. It had been reported that the putative G4-forming RNA sequences are located in some parts of most genes, thus our strategy for aptamer identification could be applicable to other proteins. It has been reported that some G4-forming RNAs in 5′ UTRs are involved in translation control; however, G4-forming excised intronic RNA function has not been revealed previously. Therefore, these findings could not only contribute to the identification of RNA aptamers but also provide new insights into the biological functioning of G4-forming RNAs located within intronic RNA sequences. Full article
(This article belongs to the Special Issue Aptamers: Past, Present, and Future)
Open AccessArticle Synthesis of Tertiary and Quaternary Amine Derivatives from Wood Resin as Chiral NMR Solvating Agents
Molecules 2015, 20(11), 20873-20886; doi:10.3390/molecules201119732
Received: 14 October 2015 / Revised: 3 November 2015 / Accepted: 8 November 2015 / Published: 23 November 2015
PDF Full-text (3877 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher’s acid (3) and its n-Bu4N salt (4)]
[...] Read more.
Chiral tertiary and quaternary amine solvating agents for NMR spectroscopy were synthesized from the wood resin derivative (+)-dehydroabietylamine (2). The resolution of enantiomers of model compounds [Mosher’s acid (3) and its n-Bu4N salt (4)] (guests) by (+)-dehydroabietyl-N,N-dimethylmethanamine (5) and its ten different ammonium salts (hosts) was studied. The best results with 3 were obtained using 5 while with 4 the best enantiomeric resolution was obtained using (+)-dehydroabietyl-N,N-dimethylmethanaminium bis(trifluoromethane-sulfonimide) (6). The compounds 5 and 6 showed a 1:1 complexation behaviour between the host and guest. The capability of 5 and 6 to recognize the enantiomers of various α-substituted carboxylic acids and their n-Bu4N salts in enantiomeric excess (ee) determinations was demonstrated. A modification of the RES-TOCSY NMR pulse sequence is described, allowing the enhancement of enantiomeric discrimination when the resolution of multiplets is insufficient. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Ultrasound-Assisted Extraction, Antioxidant and Anticancer Activities of the Polysaccharides from Rhynchosia minima Root
Molecules 2015, 20(11), 20901-20911; doi:10.3390/molecules201119734
Received: 6 October 2015 / Revised: 8 November 2015 / Accepted: 16 November 2015 / Published: 23 November 2015
Cited by 2 | PDF Full-text (2561 KB) | HTML Full-text | XML Full-text
Abstract
Box-Behnken design (BBD), one of the most common response surface methodology (RSM) methods, was used to optimize the experimental conditions for ultrasound-assisted extraction of polysaccharides from Rhynchosia minima root (PRM). The antioxidant abilities and anticancer activity of purified polysaccharide fractions were also measured.
[...] Read more.
Box-Behnken design (BBD), one of the most common response surface methodology (RSM) methods, was used to optimize the experimental conditions for ultrasound-assisted extraction of polysaccharides from Rhynchosia minima root (PRM). The antioxidant abilities and anticancer activity of purified polysaccharide fractions were also measured. The results showed that optimal extraction parameters were as follows: ultrasound exposure time, 21 min; ratio of water to material, 46 mL/g; ultrasound extraction temperature, 63 °C. Under these conditions, the maximum yield of PRM was 16.95% ± 0.07%. Furthermore, the main monosaccharides of purified fractions were Ara and Gal. PRM3 and PRM5 exhibited remarkable DPPH radical scavenging activities and reducing power in vitro. PRM3 showed strong inhibitory activities on the growth of MCF-7 cells in vitro. The above results indicate that polysaccharides from R. minima root have the potential to be developed as natural antioxidants and anticancer ingredients for the food and pharmaceutical industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle New Flavones, a 2-(2-Phenylethyl)-4H-chromen-4-one Derivative, and Anti-Inflammatory Constituents from the Stem Barks of Aquilaria sinensis
Molecules 2015, 20(11), 20912-20925; doi:10.3390/molecules201119736
Received: 14 October 2015 / Revised: 13 November 2015 / Accepted: 16 November 2015 / Published: 24 November 2015
Cited by 3 | PDF Full-text (968 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the current study, two new flavones, 4′-O-geranyltricin (1) and 3′-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6-methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together
[...] Read more.
In the current study, two new flavones, 4′-O-geranyltricin (1) and 3′-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6-methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together with 21 known compounds 424. The structures of new compounds 13 were determined through spectroscopic and MS analyses. Compounds 2, 3, 5, 6, and 810 exhibited inhibition (IC50 ≤ 12.51 μM) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3, 6, 8, 10, and 19 inhibited fMLP/CB-induced elastase release with IC50 values ≤ 15.25 μM. This investigation reveals bioactive isolates (especially 2, 3, 5, 6, 8, 9, 10, and 19) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Synthesis, Crystal Structure, Absolute Configuration and Antitumor Activity of the Enantiomers of 5-Bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide
Molecules 2015, 20(11), 20926-20938; doi:10.3390/molecules201119740
Received: 24 September 2015 / Revised: 30 October 2015 / Accepted: 18 November 2015 / Published: 24 November 2015
PDF Full-text (3273 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pyridinesulfonamide is an important fragment which has a wide range of applications in novel drugs. R- and S-isomers of 5-bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide have been synthesized, and the stereostructures have been researched. Single crystals of both compounds were obtained for X-ray analysis,
[...] Read more.
Pyridinesulfonamide is an important fragment which has a wide range of applications in novel drugs. R- and S-isomers of 5-bromo-2-chloro-N-(1-phenylethyl)pyridine-3-sulfonamide have been synthesized, and the stereostructures have been researched. Single crystals of both compounds were obtained for X-ray analysis, and the absolute configurations (ACs) have been further confirmed by electronic circular dichroism (ECD), optical rotation (OR) and quantum chemical calculations. The crystal structures and calculated geometries were extremely similar, which permitted a comparison of the relative reliabilities of ACs obtained by ECD analyses and theoretical simulation. In addition, the effect of stereochemistry on the PI3Kα kinase and anticancer activity were investigated. Compounds 10a and 10b inhibit the activity of PI3Kα kinase with IC50 values of 1.08 and 2.69 μM, respectively. Furthermore, molecular docking was performed to analyze the binding modes of R- and S-isomers. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Clones of FeSOD, MDHAR, DHAR Genes from White Clover and Gene Expression Analysis of ROS-Scavenging Enzymes during Abiotic Stress and Hormone Treatments
Molecules 2015, 20(11), 20939-20954; doi:10.3390/molecules201119741
Received: 16 October 2015 / Revised: 16 November 2015 / Accepted: 18 November 2015 / Published: 24 November 2015
Cited by 7 | PDF Full-text (2184 KB) | HTML Full-text | XML Full-text | Correction
Abstract
Increased transcriptional levels of genes encoding antioxidant enzymes play important protective roles in coping with excessive accumulation of reactive oxygen species (ROS) in plants exposed to various abiotic stresses. To fully elucidate different evolutions and functions of ROS-scavenging enzymatic genes, we isolated iron
[...] Read more.
Increased transcriptional levels of genes encoding antioxidant enzymes play important protective roles in coping with excessive accumulation of reactive oxygen species (ROS) in plants exposed to various abiotic stresses. To fully elucidate different evolutions and functions of ROS-scavenging enzymatic genes, we isolated iron superoxide dismutase (FeSOD), dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) from white clover for the first time and subsequently tested dynamic expression profiles of these genes together with previously identified other antioxidant enzyme genes including copper zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), glutathione reductase (GR), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in response to cold, drought, salinity, cadmium stress and exogenous abscisic acid (ABA) or spermidine (Spd) treatment. The cloned fragments of FeSOD, DHAR and MDHAR genes were 630, 471 and 669 bp nucleotide sequences encoding 210, 157 and 223 amino acids, respectively. Phylogenetic analysis indicated that both amino acid and nucleotide sequences of these three genes are highly conservative. In addition, the analysis of genes expression showed the transcription of GR, POD, MDHAR, DHAR and Cu/ZnSOD were rapidly activated with relatively high abundance during cold stress. Differently, CAT, APX, FeSOD, Cu/ZnSOD and MnSOD exhibited more abundant transcripts compared to others under drought stress. Under salt stress, CAT was induced preferentially (3–12 h) compared to GR which was induced later (12–72 h). Cadmium stress mainly up-regulated Cu/ZnSOD, DHAR and MDHAR. Interestingly, most of genes expression induced by ABA or Spd happened prior to various abiotic stresses. The particular expression patterns and different response time of these genes indicated that white clover differentially activates genes encoding antioxidant enzymes to mitigate the damage of ROS during various environmental stresses. Full article
(This article belongs to the Section Bioorganic Chemistry)
Open AccessArticle Carapanolides T–X from Carapa guianensis (Andiroba) Seeds
Molecules 2015, 20(11), 20955-20966; doi:10.3390/molecules201119737
Received: 29 October 2015 / Revised: 16 November 2015 / Accepted: 16 November 2015 / Published: 24 November 2015
Cited by 3 | PDF Full-text (1764 KB) | HTML Full-text | XML Full-text
Abstract
Two new mexicanolide-type limonoids, carapanolides T–U (12), and three new phragmalin-type limonoids, carapanolides V–X (35), were isolated from the seeds of Carapa guianensis (andiroba). Their structures were determined on the basis of 1D- and 2D-NMR spectroscopy. Full article
(This article belongs to the Section Natural Products)

Review

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Open AccessReview The Phe-Phe Motif for Peptide Self-Assembly in Nanomedicine
Molecules 2015, 20(11), 19775-19788; doi:10.3390/molecules201119658
Received: 30 September 2015 / Revised: 25 October 2015 / Accepted: 27 October 2015 / Published: 3 November 2015
Cited by 17 | PDF Full-text (2664 KB) | HTML Full-text | XML Full-text
Abstract
Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine,
[...] Read more.
Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, from drug delivery and biomaterials to new therapeutic paradigms. Here we discuss the various production methods for this class of compounds, and the characterization, nanomorphologies, and application of their self-assembled nanostructures. We include the most recent findings on their remarkable properties, which hold substantial promise for the creation of the next generation nanomedicines. Full article
(This article belongs to the collection Nanomedicine)
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Open AccessReview Synthesis and Chemistry of Organic Geminal Di- and Triazides
Molecules 2015, 20(11), 20042-20062; doi:10.3390/molecules201119675
Received: 5 October 2015 / Revised: 23 October 2015 / Accepted: 29 October 2015 / Published: 6 November 2015
Cited by 11 | PDF Full-text (4134 KB) | HTML Full-text | XML Full-text
Abstract
This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide
[...] Read more.
This review recapitulates all available literature dealing with the synthesis and reactivity of geminal organic di- and triazides. These compound classes are, to a large extent, unexplored despite their promising chemical properties and their simple preparation. In addition, the chemistry of carbonyl diazide (2) and tetraazidomethane (105) is described in separate sections. Full article
(This article belongs to the Special Issue Organic Azides)
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Open AccessReview α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology
Molecules 2015, 20(11), 20355-20380; doi:10.3390/molecules201119698
Received: 8 October 2015 / Revised: 29 October 2015 / Accepted: 3 November 2015 / Published: 12 November 2015
Cited by 6 | PDF Full-text (1694 KB) | HTML Full-text | XML Full-text
Abstract
α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a
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α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders. Full article
Open AccessReview Hydrogel-Based Drug Delivery Systems for Poorly Water-Soluble Drugs
Molecules 2015, 20(11), 20397-20408; doi:10.3390/molecules201119705
Received: 13 October 2015 / Revised: 2 November 2015 / Accepted: 6 November 2015 / Published: 13 November 2015
Cited by 15 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text
Abstract
Hydrogels are three-dimensional materials that can withstand a great amount of water incorporation while maintaining integrity. This allows hydrogels to be very unique biomedical materials, especially for drug delivery. Much effort has been made to incorporate hydrophilic molecules in hydrogels in the field
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Hydrogels are three-dimensional materials that can withstand a great amount of water incorporation while maintaining integrity. This allows hydrogels to be very unique biomedical materials, especially for drug delivery. Much effort has been made to incorporate hydrophilic molecules in hydrogels in the field of drug delivery, while loading of hydrophobic drugs has not been vastly studied. However, in recent years, research has also been conducted on incorporating hydrophobic molecules within hydrogel matrices for achieving a steady release of drugs to treat various ailments. Here, we summarize the types of hydrogels used as drug delivery vehicles, various methods to incorporate hydrophobic molecules in hydrogel matrices, and the potential therapeutic applications of hydrogels in cancer. Full article
(This article belongs to the collection Poorly Soluble Drugs)
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Open AccessReview Relationship between Structure and Conformational Change of the Vitamin D Receptor Ligand Binding Domain in 1α,25-Dihydroxyvitamin D3 Signaling
Molecules 2015, 20(11), 20473-20486; doi:10.3390/molecules201119713
Received: 8 October 2015 / Revised: 2 November 2015 / Accepted: 11 November 2015 / Published: 18 November 2015
Cited by 2 | PDF Full-text (875 KB) | HTML Full-text | XML Full-text
Abstract
Vitamin D Receptor (VDR) belongs to the nuclear receptor (NR) superfamily. Whereas the structure of the ligand binding domain (LBD) of VDR has been determined in great detail, the role of its amino acid residues in stabilizing the structure and ligand triggering conformational
[...] Read more.
Vitamin D Receptor (VDR) belongs to the nuclear receptor (NR) superfamily. Whereas the structure of the ligand binding domain (LBD) of VDR has been determined in great detail, the role of its amino acid residues in stabilizing the structure and ligand triggering conformational change is still under debate. There are 13 α-helices and one β-sheet in the VDR LBD and they form a three-layer sandwich structure stabilized by 10 residues. Thirty-six amino acid residues line the ligand binding pocket (LBP) and six of these residues have hydrogen-bonds linking with the ligand. In 1α,25-dihydroxyvitamin D3 signaling, H3 and H12 play an important role in the course of conformational change resulting in the provision of interfaces for dimerization, coactivator (CoA), corepressor (CoR), and hTAFII 28. In this paper we provide a detailed description of the amino acid residues stabilizing the structure and taking part in conformational change of VDR LBD according to functional domains. Full article
(This article belongs to the Section Bioorganic Chemistry)
Open AccessReview Redox Species of Redox Flow Batteries: A Review
Molecules 2015, 20(11), 20499-20517; doi:10.3390/molecules201119711
Received: 16 October 2015 / Revised: 9 November 2015 / Accepted: 9 November 2015 / Published: 18 November 2015
Cited by 17 | PDF Full-text (2048 KB) | HTML Full-text | XML Full-text
Abstract
Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its
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Due to the capricious nature of renewable energy resources, such as wind and solar, large-scale energy storage devices are increasingly required to make the best use of the renewable power. The redox flow battery is considered suitable for large-scale applications due to its modular design, good scalability and flexible operation. The biggest challenge of the redox flow battery is the low energy density. The redox active species is the most important component in redox flow batteries, and the redox potential and solubility of redox species dictate the system energy density. This review is focused on the recent development of redox species. Different categories of redox species, including simple inorganic ions, metal complexes, metal-free organic compounds, polysulfide/sulfur and lithium storage active materials, are reviewed. The future development of redox species towards higher energy density is also suggested. Full article
(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
Open AccessReview Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications
Molecules 2015, 20(11), 20551-20568; doi:10.3390/molecules201119717
Received: 14 October 2015 / Revised: 10 November 2015 / Accepted: 11 November 2015 / Published: 19 November 2015
Cited by 14 | PDF Full-text (3316 KB) | HTML Full-text | XML Full-text
Abstract
Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications.
[...] Read more.
Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD) and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors. Full article
(This article belongs to the Special Issue Chemoinformatics)
Open AccessReview Immobilization of Metal Hexacyanoferrate Ion-Exchangers for the Synthesis of Metal Ion Sorbents—A Mini-Review
Molecules 2015, 20(11), 20582-20613; doi:10.3390/molecules201119718
Received: 27 August 2015 / Revised: 27 October 2015 / Accepted: 6 November 2015 / Published: 19 November 2015
Cited by 14 | PDF Full-text (6098 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Metal hexacyanoferrates are very efficient sorbents for the recovery of alkali and base metal ions (including radionuclides such as Cs). Generally produced by the direct reaction of metal salts with potassium hexacyanoferrate (the precursors), they are characterized by ion-exchange and structural properties that
[...] Read more.
Metal hexacyanoferrates are very efficient sorbents for the recovery of alkali and base metal ions (including radionuclides such as Cs). Generally produced by the direct reaction of metal salts with potassium hexacyanoferrate (the precursors), they are characterized by ion-exchange and structural properties that make then particularly selective for Cs(I), Rb(I) and Tl(I) recovery (based on their hydrated ionic radius consistent with the size of the ion-exchanger cage), though they can bind also base metals. The major drawback of these materials is associated to their nanometer or micrometer size that makes them difficult to recover in large-size continuous systems. For this reason many techniques have been designed for immobilizing these ion-exchangers in suitable matrices that can be organic (mainly polymers and biopolymers) or inorganic (mineral supports), carbon-based matrices. This immobilization may proceed by in situ synthesis or by entrapment/encapsulation. This mini-review reports some examples of hybrid materials synthesized for the immobilization of metal hexacyanoferrate, the different conditionings of these composite materials and, briefly, the parameters to take into account for their optimal design and facilitated use. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Organic Chemistry)
Open AccessReview Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities
Molecules 2015, 20(11), 20614-20641; doi:10.3390/molecules201119721
Received: 3 July 2015 / Revised: 21 August 2015 / Accepted: 23 September 2015 / Published: 19 November 2015
Cited by 31 | PDF Full-text (1177 KB) | HTML Full-text | XML Full-text
Abstract
Ursolic acid (UA) is a natural terpene compound exhibiting many pharmaceutical properties. In this review the current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented. Particular attention
[...] Read more.
Ursolic acid (UA) is a natural terpene compound exhibiting many pharmaceutical properties. In this review the current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented. Particular attention has been paid to the application of ursolic acid as an anti-cancer agent; it is worth noticing that clinical tests suggesting the possibility of practical use of UA have already been conducted. Amongst other pharmacological properties of UA one can mention protective effect on lungs, kidneys, liver and brain, anti-inflammatory properties, anabolic effects on skeletal muscles and the ability to suppress bone density loss leading to osteoporosis. Ursolic acid also exhibits anti-microbial features against numerous strains of bacteria, HIV and HCV viruses and Plasmodium protozoa causing malaria. Full article
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Open AccessReview The Effect of Low Monotonic Doses of Zearalenone on Selected Reproductive Tissues in Pre-Pubertal Female Dogs—A Review
Molecules 2015, 20(11), 20669-20687; doi:10.3390/molecules201119726
Received: 11 September 2015 / Revised: 22 October 2015 / Accepted: 12 November 2015 / Published: 19 November 2015
Cited by 6 | PDF Full-text (1164 KB) | HTML Full-text | XML Full-text
Abstract
The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose
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The growing interest in toxic substances combined with advancements in biological sciences has shed a new light on the problem of mycotoxins contaminating feeds and foods. An interdisciplinary approach was developed by identifying dose-response relationships in key research concepts, including the low dose theory of estrogen-like compounds, hormesis, NOAEL dose, compensatory response and/or food tolerance, and effects of exposure to undesirable substances. The above considerations increased the researchers’ interest in risk evaluation, namely: (i) clinical symptoms associated with long-term, daily exposure to low doses of a toxic compound; and (ii) dysfunctions at cellular or tissue level that do not produce clinical symptoms. Research advancements facilitate the extrapolation of results and promote the use of novel tools for evaluating the risk of exposure, for example exposure to zearalenone in pre-pubertal female dogs. The arguments presented in this paper suggest that low doses of zearalenone in commercial feeds stimulate metabolic processes and increase weight gains. Those processes are accompanied by lower proliferation rates in the ovaries, neoangiogenesis and vasodilation in the ovaries and the uterus, changes in the steroid hormone profile, and changes in the activity of hydroxysteroid dehydrogenases. All of the above changes result from exogenous hyperestrogenizm. Full article
(This article belongs to the Special Issue Natural Toxins)
Open AccessReview Current Research on Antiepileptic Compounds
Molecules 2015, 20(11), 20741-20776; doi:10.3390/molecules201119714
Received: 29 July 2015 / Revised: 3 November 2015 / Accepted: 6 November 2015 / Published: 20 November 2015
Cited by 4 | PDF Full-text (10832 KB) | HTML Full-text | XML Full-text
Abstract
Epilepsy affects about 1% of the world’s population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development
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Epilepsy affects about 1% of the world’s population. Due to the fact all antiepileptic drugs (AEDs) have some undesirable side effects and about 30% of epileptic patients are not seizure-free with the existing AEDs, there is still an urgent need for the development of more effective and safer AEDs. Based on our research work on antiepileptic compounds and other references in recent years, this review covers the reported work on antiepileptic compounds which are classified according to their structures. This review summarized 244 significant anticonvulsant compounds which are classified by functional groups according to the animal model data, although there are some limitations in the data. This review highlights the properties of new compounds endowed with promising antiepileptic properties, which may be proven to be more effective and selective, and possibly free of unwanted side effects. The reviewed compounds represent an interesting possibility to overcome refractory seizures and to reduce the percentage of patients with a poor response to drug therapy. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessReview DNA Catalysis: The Chemical Repertoire of DNAzymes
Molecules 2015, 20(11), 20777-20804; doi:10.3390/molecules201119730
Received: 25 October 2015 / Revised: 10 November 2015 / Accepted: 11 November 2015 / Published: 20 November 2015
Cited by 27 | PDF Full-text (5193 KB) | HTML Full-text | XML Full-text
Abstract
Deoxyribozymes or DNAzymes are single-stranded catalytic DNA molecules that are obtained by combinatorial in vitro selection methods. Initially conceived to function as gene silencing agents, the scope of DNAzymes has rapidly expanded into diverse fields, including biosensing, diagnostics, logic gate operations, and the
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Deoxyribozymes or DNAzymes are single-stranded catalytic DNA molecules that are obtained by combinatorial in vitro selection methods. Initially conceived to function as gene silencing agents, the scope of DNAzymes has rapidly expanded into diverse fields, including biosensing, diagnostics, logic gate operations, and the development of novel synthetic and biological tools. In this review, an overview of all the different chemical reactions catalyzed by DNAzymes is given with an emphasis on RNA cleavage and the use of non-nucleosidic substrates. The use of modified nucleoside triphosphates (dN*TPs) to expand the chemical space to be explored in selection experiments and ultimately to generate DNAzymes with an expanded chemical repertoire is also highlighted. Full article
(This article belongs to the Special Issue Nanozymes and Beyond)
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Open AccessReview Phytochelators Intended for Clinical Use in Iron Overload, Other Diseases of Iron Imbalance and Free Radical Pathology
Molecules 2015, 20(11), 20841-20872; doi:10.3390/molecules201119725
Received: 2 September 2015 / Revised: 3 November 2015 / Accepted: 9 November 2015 / Published: 23 November 2015
Cited by 3 | PDF Full-text (1913 KB) | HTML Full-text | XML Full-text
Abstract
Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving
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Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)—plant, chele (χηλή)—claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries. Full article
(This article belongs to the Section Metabolites)
Open AccessReview Quaternary Alkylammonium Conjugates of Steroids: Synthesis, Molecular Structure, and Biological Studies
Molecules 2015, 20(11), 20887-20900; doi:10.3390/molecules201119735
Received: 23 October 2015 / Revised: 15 November 2015 / Accepted: 17 November 2015 / Published: 23 November 2015
Cited by 1 | PDF Full-text (3642 KB) | HTML Full-text | XML Full-text
Abstract
The methods of synthesis as well as physical, spectroscopic (1H-NMR, 13C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological
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The methods of synthesis as well as physical, spectroscopic (1H-NMR, 13C-NMR, and FT-IR, ESI-MS), and biological properties of quaternary and dimeric quaternary alkylammonium conjugates of steroids are presented. The results were contrasted with theoretical calculations (PM5 methods) and potential pharmacological properties (PASS). Alkylammonium sterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine. Full article
(This article belongs to the Section Organic Synthesis)

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Open AccessCorrection Correction: Wang L.K., et al. Two New Lanostane Triterpenoids from the Branches and Leaves of Polyalthia oblique. Molecules 2014, 19, 7621–7628
Molecules 2015, 20(11), 20268; doi:10.3390/molecules201119690
Received: 29 October 2015 / Accepted: 2 November 2015 / Published: 11 November 2015
PDF Full-text (334 KB) | HTML Full-text | XML Full-text
Abstract
The authors wish to make the following correction to their paper [1], published recently in Molecules. [...] Full article
(This article belongs to the collection Bioactive Compounds)

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